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Ohkubo, M., G. Uehara, J. Beyer, M. Mimura, H. Tanaka, K. Ehara, S. Tanaka et al. „Standard measurement method for normal state resistance and critical current of resistively shunted Josephson junctions“. Superconductor Science and Technology 35, Nr. 4 (14.02.2022): 045002. http://dx.doi.org/10.1088/1361-6668/ac4f3b.
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Abstract An important parameter of Josephson junctions (JJs) is the product of normal state resistance (R n) and critical current (I c) for designing superconductor analogue devices or digital circuits. Determination of R n and I c from voltage–current (U–I) characteristic curves often faces difficulties; in particular I c is considerably reduced by intrinsic thermal or extrinsic electrical noises. Here, we propose a standard measurement method of R n and intrinsic critical current (I ci) for high-T c superconductor (HTS) grain boundary JJs operated in liquid nitrogen and low-T c superconductor (LTS) multilayer superconductor/normal-conductor/superconductor (SNS) JJs in liquid helium. The applicable condition of this method is that both HTS and LTS JJs have U–I curves compatible with resistively-shunted junction (RSJ) model. Both R n and I ci values are extracted by combining a geometric mean criterion to select a data set and a least-squares fitting method with the RSJ model, eliminating two distortion effects on U–I curves: noise-rounding and self-heating. The combined method ensures relative standard uncertainty values of 1.9% for R n and 8% for I ci or better, when the users follow the standard protocol. It is demonstrated that the combined method is valid for d-wave HTS JJs near 77 K, regardless of peculiarities such as 0–π junction transition in d-wave superconductors at lower temperatures, and s-wave LTS SNS JJs with a wide range of junction parameters. This work is the first step to facilitate standardization for superconductor electronics with JJs.
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Doucet, M. Y., T. R. Jones und A. W. Ford-Hutchinson. „Responses of equine trachealis and lung parenchyma to methacholine, histamine, serotonin, prostanoids, and leukotrienes in vitro“. Canadian Journal of Physiology and Pharmacology 68, Nr. 3 (01.03.1990): 379–83. http://dx.doi.org/10.1139/y90-053.
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The responses of equine trachealis and lung parenchymal strips to a range of contractile agonists were studied. Equine trachealis responded to methacholine > histamine > serotonin as shown by the maximal responses but failed to respond to either leukotrienes (LT), prostaglandin F2α, or U-44069. Equine parenchymal strips showed considerable tonal activity and responded to LTD4[Formula: see text]LTC4 > U-44069 = LTE4 > methacholine [Formula: see text] histamine [Formula: see text] serotonin > prostaglandin F2α as determined through pD2 values. Neither the concentration response curve to LTD4 nor the intrinsic tonal activity of the preparations was modified by pretreatment with either atropine or indomethacin, although the maximal response to LTD4 was reversed by addition of the LTD4 receptor antagonist, MK-571. Thus arachidonic acid metabolites, including LTs, must be considered potential mediators of equine small airway disease, a potential model of human bronchial asthma.Key words: horse, leukotrienes, U-44069, trachea, lung parenchyma.
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He, Shuai, Yinghua Zhang, Zhian Huang, Ge Zhang und Yukun Gao. „Influence of Internal Structure and Composition on Head’s Local Thermal Sensation and Temperature Distribution“. Atmosphere 11, Nr. 2 (21.02.2020): 218. http://dx.doi.org/10.3390/atmos11020218.
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A personalized thermal environment is an effective way to ensure a good thermal sensation for individuals. Since local thermal sensation and temperature distribution are affected by individual physiological differences, it is necessary to study the effects of physiological parameters. The purpose of this study was to investigate the effects of internal structures and tissue composition on head temperature distribution and thermal sensation. A new mathematical model based on fuzzy logic control was established, the internal structure and tissue composition of the head were obtained by magnetic resonance imaging (MRI), and the local thermal sensation (LTS) index was used to evaluate the thermal sensation. Based on the mathematical model and the real physiological data, the head temperature and local sensation changes under different parameters were investigated, and the sensitivity of thermal sensation relative to the differences in tissue thickness was analyzed. The results show that skin tissue had the highest influence ( C s k i n = 0.0180 ) on head temperature, followed by muscle tissue ( C m u s c l e = 0.0127 ), and the influence of adipose tissue ( C f a t = 0.0097 ) was the lowest. LTS was most sensitive to skin thickness variation, with an average sensitivity coefficient of 1.58, while the muscle tissue had an average sensitivity coefficient of 0.2, and the sensitivity coefficient of fat was relatively small, at a value of 0.04.
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Telzerow, Eva, Dennis Görlich, Maja Rothenberg-Thurley, Maria Cristina Sauerland, Anna Sophia Moret, Friederike H. A. Mumm, Susanne Amler et al. „Quality of Life and Life Satisfaction in AML Long-Term Survivors: Primary Results of the AMLCG-Survivorship Study“. Blood 138, Supplement 1 (05.11.2021): 2289. http://dx.doi.org/10.1182/blood-2021-147027.
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Abstract Introduction An increasing proportion of patients with Acute Myeloid Leukemia (AML) become long-term survivors. Somatic and psycho-social outcomes are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment. Methods We designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status and conducted a questionnaire-based study collecting data from AML long term survivors (AML-LTS) and their physicians. This report focuses on overall and health-related quality of life. Somatic, especially cardiovascular, morbidity in AML-LTS are reported separately (Moret et al.). The primary aim of this study was to compare quality of life (QoL, measured by the FACT-G questionnaire) and general and health-related life satisfaction (gLS/hLS, measured by the FLZ-M questionnaire) of AML-LTS with normative data of German adults who were not diagnosed with AML (Holzner et al. 2009; Daig et al. 2009). FLZ-M and FACT-G scores were standardized relative to the normal population mean and standard deviation, stratified by sex and age. These z-scores were then tested against the fixed value 0 (indicating no difference between AML-LTS and the general population) using Mann-Whitney U-tests. Our statistical design incorporated a sequentially rejective testing procedure to maintain the multiple testing significance level at 5%, using a graphical model as described by Bretz et al. (2009). Results 427 former AML patients who had been enrolled in AMLCG trials (AMLCG-1999, AMLCG-2004, AMLCG-2008) or the AMLCG patient registry, participated in this study between 5 and 18.6 years [y] after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (alloSCT). A relapse occurred in 24% of the participants. Unexpectedly, quality of life and general life satisfaction summary scores were significantly higher in AML-LTS (p<.001) compared to adults without the diagnosis of AML, although most differences on QoL subscales relative to the general population were small and very likely not clinically relevant. No statistical difference between AML-LTS and normal adults was found for health-related life satisfaction (hLS). Notably, a subgroup of participants (26%) reported poor physical well-being (PWB), indicated by a FACT PWB subscore more than one standard deviation (SD) below the age- and sex-matched general population value (Figure A). This resulted in poor overall QoL (i.e. >1 SD below normal) for 13% of the participants (Figure B). To identify factors potentially associated with poor overall QoL, we constructed a logistic regression model including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloSCT) and additional covariables that associated with QoL in univariate analyses (Table C). We found that participants with younger age, male sex, lower educational level, shorter time since diagnosis and a altered financial situation reported significantly lower QoL. No influence was found for other characteristics including treatment (alloSCT vs. no alloSCT), previous relapse, or de novo vs. secondary or therapy-related AML. Discussion Unlike previous studies of AML survivorship, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insight into long-term quality of life. Our study establishes that overall QoL in AML long-term survivors is comparable to the general population. Improvement of QoL continues beyond five years post diagnosis. Importantly, disease- and treatment-related factors, such as prior relapse or status post allogeneic transplantation, are not associated with overall QoL. However, we were able to identify risk factors for worse QoL (younger age, male sex, alteration of the financial situation), delineating a subgroup of patients that may still have a need for targeted psycho-social interventions five or more years after an AML diagnosis. Figure 1 Figure 1. Disclosures Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hiddemann: Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Metzeler: AbbVie: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Celgene/BMS: Consultancy, Honoraria, Research Funding.
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Bakhsham, Milad, Mahdi Hosseinpour, Masoumeh Ayeneh, Hossein Karimi und Parisa Parandavar. „Identifying and Analyzing the Application of the Internet of Things in Supply Pharmaceutical Chain Agility in post COVID -19“. Journal of Health and Biomedical Informatics 10, Nr. 1 (22.05.2023): 57–69. http://dx.doi.org/10.34172/jhbmi.2023.14.
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Introduction: The internet of Things has become more popular as a new technology since the advent of wire less technology , and attracted attention from supply chain management promoters. This study aimed to identify and analyze IoT applications in the pharmaceutical supply chain agility in the post -COVID -19 era Method: We first review previous studies in appl ications of IoT in pharmaceutical supply chain agility and identified the findings through qualitative content analysis. Then, the identified factors were given to 20 management and information technology experts to confirm and validat e. Results: The resu lts showed that IoT applications on the pharmaceutical supply chain agility in 9 components and 50 indicators. First of all, the most important factor is faster communication with other stakeholders (suppliers, manufacturers, distributors, and customers) u sing the IoT in the supply chain . Secondly, the use of IoT for drug production; manufacturers invest in technologies that lead to lower operating costs in the long term, because network devices and sensors do not make mistakes, do not need rest and trainin g, and do not take vacations. Therefore, they increase the agility of the production process and are a reliable and cost -effective alternative for productivity in production. Conclusion: The wide applications of the proposed model indicate the need to cons ider the use of the IoT in the pharmaceutical industry supply chain in order to improve overall supply chain performance and focus on supply chain agility.
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Reddy, S. Reddy Vamshidhar, und Sanjay Dhar Roy. „SBT (Sense Before Transmit) Based LTE Licenced Assisted Access for 5 GHz Unlicensed Spectrum“. Wireless Personal Communications 119, Nr. 3 (03.03.2021): 2069–81. http://dx.doi.org/10.1007/s11277-021-08318-1.
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AbstractUtilization of unlicensed spectrum under licensed assisted access ensuring fair co-existence with Wi-Fi networks is a good solution to address immense usage of mobile data. Radio communication operation of LTE in unlicensed frequency band is referred as LTE-unlicensed (LTE-U) or LTE-licensed assisted access. In this paper, we consider a HGNW in which coverage area of Wireless-Fidelity (Wi-Fi)’s Access Point is integrated within the LTE-U small base station’s cellular network coverage area. To overcome the disadvantages of existing LTE-U technics like carrier sense adaptive transmission and listen before talk, we proposed a new methodology i.e., sense before transmit in this paper by adopting a transmit power control mechanisms using reciprocity theorem based on the channel state information to assign the secondary carriers in the uplink as well as in the downlink directions in the unlicensed spectrum to carry the traffic. In our proposal, LTE-U users are allowed to use the unlicensed spectrum provided that the interference produced at Wi-Fi users due to LTE-U activities is remained below a certain threshold. We evaluated the performance of proposed network model in terms of outage probability and achievable throughputs.
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Girmay, Merkebu, Vasilis Maglogiannis, Dries Naudts, Adnan Shahid und Ingrid Moerman. „Coexistence Scheme for Uncoordinated LTE and WiFi Networks Using Experience Replay Based Q-Learning“. Sensors 21, Nr. 21 (21.10.2021): 6977. http://dx.doi.org/10.3390/s21216977.
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Nowadays, broadband applications that use the licensed spectrum of the cellular network are growing fast. For this reason, Long-Term Evolution-Unlicensed (LTE-U) technology is expected to offload its traffic to the unlicensed spectrum. However, LTE-U transmissions have to coexist with the existing WiFi networks. Most existing coexistence schemes consider coordinated LTE-U and WiFi networks where there is a central coordinator that communicates traffic demand of the co-located networks. However, such a method of WiFi traffic estimation raises the complexity, traffic overhead, and reaction time of the coexistence schemes. In this article, we propose Experience Replay (ER) and Reward selective Experience Replay (RER) based Q-learning techniques as a solution for the coexistence of uncoordinated LTE-U and WiFi networks. In the proposed schemes, the LTE-U deploys a WiFi saturation sensing model to estimate the traffic demand of co-located WiFi networks. We also made a performance comparison between the proposed schemes and other rule-based and Q-learning based coexistence schemes implemented in non-coordinated LTE-U and WiFi networks. The simulation results show that the RER Q-learning scheme converges faster than the ER Q-learning scheme. The RER Q-learning scheme also gives 19.1% and 5.2% enhancement in aggregated throughput and 16.4% and 10.9% enhancement in fairness performance as compared to the rule-based and Q-learning coexistence schemes, respectively.
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Zhiqun, Hu, Lu Zhaoming, Lin Shangjuan, Wen Xiangming und Xu Hen. „Performance analysis of LTE-U coexistence network with WiFi using queueing model“. Journal of China Universities of Posts and Telecommunications 24, Nr. 5 (Oktober 2017): 1–7. http://dx.doi.org/10.1016/s1005-8885(17)60227-9.
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Baswade, Anand M., Mohith Reddy, Antony Franklin A., Bheemarjuna Reddy Tamma und Vanlin Sathya. „Performance analysis of spatially distributed LTE-U/NR-U and Wi-Fi networks: An analytical model for coexistence study“. Journal of Network and Computer Applications 191 (Oktober 2021): 103157. http://dx.doi.org/10.1016/j.jnca.2021.103157.
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Przesmycki, Rafał, und Marek Bugaj. „Crescent Microstrip Antenna for LTE-U and 5G Systems“. Electronics 11, Nr. 8 (09.04.2022): 1201. http://dx.doi.org/10.3390/electronics11081201.
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The field of wireless cellular network technology has seen a significant development in recent years, allowing the emergence of many new applications in addition to the traditional mobile phone calls. We are currently implementing the 5G system, which is replacing the previous cellular technologies on the market. Parallel to the development of cellular technologies, wireless local networks based on the IEEE 802.11× standards are rapidly spreading. The desire to use the advantages of both mobile telephony and wireless local networks has led to the idea of integrating the currently used communication systems in one device and requires a well-designed antenna, which should be given a lot of attention when designing the radio system. This article presents the proposed model of a two-band microstrip antenna for which the main assumption is its operating frequencies in the LTE-U (LTE-Unlicensed) band and one of the 5G system bands. The antenna dimensions and parameters have been calculated, simulated, and optimized using CST Microwave Studio software. The developed antenna has a compact structure with dimensions of (60 × 40 × 1.57) mm. The dielectric material RT Duroid 5880 with a dielectric constant εr = 2.2 and thickness h = 1.57 mm was used as a substrate for the antenna construction. The article presents an analysis of the results of simulation and measurements of selected electrical parameters and radiation characteristics of the proposed antenna. The antenna described in the article, working in 5G systems and LTE-U systems, is characterized by two operating bands with center frequencies equal to 3.52 GHz and 5.37 GHz, a low reflection coefficient (for resonances −31.54 dB and −23.16 dB), a gain value of 4.45 dBi, a wide frequency band of 3.0 GHz (68.18%), and a high energy efficiency in the range of 80–96.68%.
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Muto, Atsushi, Takehisa Kitazawa, Kazutaka Yoshihasi, Minako Takeda, Tetsuhiro Soeda, Tomoyuki Igawa, Zenjiro Sampei et al. „Hemostatic Effect of a Novel Bispecific Antibody (ACE910) Against Activated Factor IX and Factor X in an Acquired Hemophilia A Model“. Blood 120, Nr. 21 (16.11.2012): 42. http://dx.doi.org/10.1182/blood.v120.21.42.42.
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Abstract Abstract 42 Background: Hemophilia A is treated by intravenous replacement therapy with factor VIII (FVIII), either on demand to resolve bleeding or as a prophylactic to prevent bleeding. Recently, routine prophylactic treatment is recommended to effectively prevent bleeding and to reduce bleeding-related chronic joint damage. However, the need for frequent intravenous injections of FVIII negatively affects patients' quality of life and their adherence to the routine prophylactic regimen. More importantly, approximately 30% of severe hemophilia A patients develop inhibitory antibodies toward the injected FVIII, rendering the replacement therapy ineffective. To overcome these drawbacks, we generated a bispecific antibody (termed ACE910) against activated factor IX (FIXa) and factor X (FX), which mimics the cofactor function of FVIII. Objectives: The aims of the present study were to examine the FVIII-mimetic cofactor activity of ACE910 in vitro and its hemostatic activity in vivo. Methods: The FVIII-mimetic cofactor activity of ACE910 was evaluated by a thrombin generation assay in human FVIII-deficient plasma as well as by an enzymatic assay using purified coagulation factors. For in vivo studies, an acquired hemophilia A model was established in cynomolgus monkeys by a single intravenous injection of mouse monoclonal anti-FVIII neutralizing antibody, which was cross-reactive to cynomolgus monkey FVIII but not to porcine FVIII. After artificial bleeding had been induced, ACE910 or porcine FVIII was intravenously administered in a single dose or in twice-daily repeated doses, respectively. Bleeding symptoms, including anemia and skin bruising, were monitored for three days. A pharmacokinetic study of ACE910 was also performed with a single intravenous or subcutaneous administration to cynomolgus monkeys. Results: ACE910 concentration-dependently showed FVIII-mimetic cofactor activity in the enzymatic assay and improved thrombin generation parameters in human FVIII-deficient plasma. Intravenous administration of ACE910 (a single dose of 3 mg/kg) significantly reduced the bleeding symptoms in the acquired hemophilia A model of a non-human primate. This hemostatic effect was comparable to twice-daily intravenous administration of porcine FVIII (repeated doses of 10 U/kg). The half-life of ACE910 was approximately three weeks for both single intravenous and subcutaneous administrations. The subcutaneous bioavailability of ACE910 was nearly 100%. Conclusion: The bispecific antibody against FIXa and FX, ACE910, exerted FVIII-mimetic cofactor activity in vitro. Furthermore, a single dose of ACE910 demonstrated hemostatic activity comparable to twice-daily repeated doses of 10 U/kg porcine FVIII in vivo. Moreover, ACE910 exhibited high subcutaneous bioavailability and approximately three-week half-life in a non-human primate. Our bispecific antibody against FIXa and FX is a subcutaneously injectable, long-acting agent that removes the need to consider the induction or presence of FVIII inhibitors and may establish a novel principle for the prophylactic treatment of hemophilia A patients. Disclosures: Muto: Chugai Pharmaceutical Co., Ltd.: Employment. Kitazawa:Chugai Pharmaceutical Co., Ltd.: Employment. Yoshihasi:Chugai Pharmaceutical Co., Ltd.: Employment. Takeda:Chugai Pharmaceutical Co., Ltd.: Employment. Soeda:Chugai Pharmaceutical Co., Ltd.: Employment. Igawa:Chugai Pharmaceutical Co., Ltd.: Employment. Sampei:Chugai Pharmaceutical Co., Ltd.: Employment. Sakamoto:Chugai Pharmaceutical Co., Ltd.: Employment. Okuyama-Nishida:Chugai Pharmaceutical Co., Ltd.: Employment. Saito:Chugai Pharmaceutical Co., Ltd.: Employment. Kawabe:Chugai Pharmaceutical Co., Ltd.: Employment. Shima:Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding. Hattori:Chugai Pharmaceutical Co., Ltd.: Employment.
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Ogiwara, Kenichi, Shoko Furukawa, Kana Sasai, Keito Inaba, Takehisa Kitazawa und Keiji Nogami. „Effects of Bypassing Hemostatic Agents in the Co-Presence of NXT007, Emicizumab-Based Engineered Bispecific Antibody to Fixa/Fx, Using in Vitro Global Assays: Rough Indicators for Their Concomitant Use“. Blood 138, Supplement 1 (05.11.2021): 2114. http://dx.doi.org/10.1182/blood-2021-149412.
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Abstract Background: NXT007, emicizumab (Emi)-based engineered therapeutic bispecific antibody which increases tissue factor (TF)-triggered thrombin generation (TG) potential of factor(F) VIII-deficient plasma to non-hemophiliac ranges at around 5-30 μg/mL (Yamaguchi, ASH 2020), is currently in a phase 1/2 clinical study. In the clinical settings under NXT007-prophylaxis, bypassing hemostatic agents (BPAs), such as activated prothrombin complex concentrates (aPCC) and recombinant(r) FVIIa, may be concomitantly administered. Under Emi-prophylaxis, repeated doses of aPCC impose a thrombotic risk. Against the risk, NHF's Medical and Scientific Advisory Council (MASAC) recommends ≤50 U/kg and ≤100 U/kg of aPCC as initial dose and one day dosage, respectively. In case of NXT007-prophylaxis, concomitant-use with BPAs should be also carefully managed and thus basic non-clinical combination data are needed. Objectives: To examine in vitro effects of BPAs in the co-presence of NXT007 for providing rough indicators for determining their safe doses. Methods: First, TF-triggered TG assay was performed using commercial FVIII-deficient plasma. rFVIII, rFVIIa or aPCC was spiked in the co-presence of NXT007 or Emi (0.1-50 μg/mL). Second, the TG assay and whole blood clot viscosity test (ROTEM) using Ca 2+-trigger was performed using healthy volunteer's blood incubated with anti-FVIII antibodies (HA model), where aPCC or rFVIIa was spiked in the co-presence of NXT007. Third, ROTEM was performed as above using whole blood from persons with hemophilia A (PwHA) under Emi- or FVIII-prophylaxis. Results: Peak height of TF-triggered TG assay using FVIII-deficient plasma was increased by spiking each of the agents (rFVIII, rFVIIa or aPCC) in the co-presence of NXT007 (0.1-50 μg/mL). Peak height increase by rFVIII under NXT007 was roughly additive. Peak height increase by each BPA under NXT007 was synergistic. Synergistic effect by aPCC was more intensive than that by rFVIIa. The combination effect of 0.1 U/mL aPCC and 0.1-50 μg/mL NXT007 on peak height did not exceed that of 0.5 U/mL aPCC and 50 μg/mL Emi. Peak height at 2 μg/mL NXT007 alone was comparable to that at 50 μg/mL Emi alone. When adding BPAs to these two settings, similar synergistic effects were observed. It suggested that NXT007's combination actions with BPAs were qualitatively similar to Emi's. In the TG assay using the HA model plasma (n=2), the combined effect of aPCC and NXT007 was similarly confirmed. In ROTEM using the same HA model whole blood (n=2), clotting time (ROTEM-CT, 7380±605 sec) was shortened by spiking 5 μg/mL NXT007 (791±148 sec) to yield normal levels (1521±110 sec). Spiked aPCC (0.13, 0.65 U/mL in whole blood, equivalent to ~10, ~50 U/kg infusion) shortened ROTEM-CT (1228±549, 435±54 sec) and further shortened it in the co-presence of 5 or 15 μg/mL NXT007 (171±11, 113±1* or 143±4, 90±5* sec [* significantly ( p<0.05) shorter than that of the Emi-treated PwHA blood spiking 0.65 U/mL aPCC, 162±21 sec)]. In PwHA without Emi-prophylaxis (n=2), ROTEM-CT (5148±1290 sec) was shortened by spiking 5 or 15 μg/mL NXT007 (1598±482 or 1116±14 sec) to non-hemophiliac levels (20 IU/dL rFVIII, 1569±222 sec). Spiked aPCC (0.13, 0.65 U/mL) shortened ROTEM-CT (1383±322, 680±84 sec) and further shortened it in the co-presence of 5 or 15 μg/mL NXT007 (230±35, 144±4 or 193±11, 121±0* sec). Spiked rFVIIa also shortened ROTEM-CT in the co-presence of NXT007, but the intensity was less than spiked aPCC. ROTEM using blood from PwHA under Emi-prophylaxis (n=3) were also performed and demonstrated that the effects by co-spiking BPAs and NXT007 were roughly consistent with those using PwHA blood without Emi-prophylaxis. These ROTEM data indicated that the combined effect of 0.13 U/mL aPCC and 5-15 μg/mL NXT007 was less intensive than that of 0.65 U/mL aPCC spiked to the Emi-treated PwHA blood, while that of 0.65 U/mL aPCC and 5-15 μg/mL NXT007 had more intensive effect (Table). Conclusion: In considering concomitant use of BPA under NXT007-prophylaxis, dose of aPCC should be more carefully determined than that of rFVIIa. In this non-clinical study, the combined effect of ~0.13 U/mL aPCC (equivalent to ~10 U/kg infusion) and ~15 μg/mL NXT007 did not exceed that of 0.65 U/mL aPCC (50 U/kg infusion) under Emi-prophylaxis situation corresponding to the upper limit of initial concomitant dose recommended by MASAC, which might be rough indicators in future clinical settings. Figure 1 Figure 1. Disclosures Ogiwara: Chugai Pharmaceutical Co., Ltd.: Consultancy, Research Funding. Furukawa: Chugai Pharmaceutical Co., Ltd.: Research Funding. Sasai: Chugai Pharmaceutical Co., Ltd.: Research Funding. Inaba: Chugai Pharmaceutical Co., Ltd.: Current Employment. Kitazawa: Chugai Pharmaceutical Co., Ltd.: Current Employment, Current equity holder in publicly-traded company. Nogami: Chugai Pharmaceutical Co., Ltd.: Consultancy, Research Funding.
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Liang, Hao, Hongli Zhao, Shuo Wang und Yong Zhang. „LTE-U based Train to Train Communication System in CBTC: System Desin and Reliability Analysis“. Wireless Communications and Mobile Computing 2020 (30.12.2020): 1–14. http://dx.doi.org/10.1155/2020/8893631.
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Communication-Based Train Control (CBTC) system is a critical signal system to ensure rail transit’s safe operation. Compared with the train-ground CBTC system, the train control system based on train-to-train (T2T) communication has the advantages of fast response speed, simple structure, and low operating cost. As the core part of the train control system based on T2T communication, the reliability of the data communication system (DCS) is of great significance to ensure the train’s safe and efficient operation. According to the T2T communication system requirements, this paper adopts Long-Term Evolution-Unlicensed (LTE-U) technology to design the DCS structure and establishes the reliability model of the communication system based on Deterministic and Stochastic Petri Nets (DSPN). Based on testing the real line’s communication performance parameters, the DSPN model is simulated and solved by π -tool, and the reliability index of the system is obtained. The research results show that the LTE-U-based T2T communication system designed in this paper meets the train control system’s needs for communication transmission. This paper’s reliability evaluation method can complete the reliability modeling of train control DCS based on T2T communication. The research in this paper will provide a strong practical and theoretical basis for the design and optimization of train control DCS based on T2T communication.
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Mohammad-Rahimi, Hossein, Shankeeth Vinayahalingam, Erfan Mahmoudinia, Parisa Soltani, Stefaan J. Bergé, Joachim Krois und Falk Schwendicke. „Super-Resolution of Dental Panoramic Radiographs Using Deep Learning: A Pilot Study“. Diagnostics 13, Nr. 5 (06.03.2023): 996. http://dx.doi.org/10.3390/diagnostics13050996.
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Using super-resolution (SR) algorithms, an image with a low resolution can be converted into a high-quality image. Our objective was to compare deep learning-based SR models to a conventional approach for improving the resolution of dental panoramic radiographs. A total of 888 dental panoramic radiographs were obtained. Our study involved five state-of-the-art deep learning-based SR approaches, including SR convolutional neural networks (SRCNN), SR generative adversarial network (SRGAN), U-Net, Swin for image restoration (SwinIr), and local texture estimator (LTE). Their results were compared with one another and with conventional bicubic interpolation. The performance of each model was evaluated using the metrics of mean squared error (MSE), peak signal-to-noise ratio (PNSR), structural similarity index (SSIM), and mean opinion score by four experts (MOS). Among all the models evaluated, the LTE model presented the highest performance, with MSE, SSIM, PSNR, and MOS results of 7.42 ± 0.44, 39.74 ± 0.17, 0.919 ± 0.003, and 3.59 ± 0.54, respectively. Additionally, compared with low-resolution images, the output of all the used approaches showed significant improvements in MOS evaluation. A significant enhancement in the quality of panoramic radiographs can be achieved by SR. The LTE model outperformed the other models.
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Petzer, A. L., C. J. Eaves, M. J. Barnett und A. C. Eaves. „Selective Expansion of Primitive Normal Hematopoietic Cells in Cytokine-Supplemented Cultures of Purified Cells From Patients With Chronic Myeloid Leukemia“. Blood 90, Nr. 1 (01.07.1997): 64–69. http://dx.doi.org/10.1182/blood.v90.1.64.
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Abstract We have previously reported that primitive normal hematopoietic cells detectable as long-term culture-initiating cells (Ph-LTC-IC) are present at high levels in the blood of some patients with chronic myeloid leukemia (CML). We now show that this population can be expanded several-fold when highly purified CD34+CD38− cells isolated from the blood of such patients are cultured for 10 days in a serum-free medium containing 100 ng/mL of Flt3-ligand and Steel factor and 20 ng/mL of interleukin-3 (IL-3) and IL-6, and granulocyte colony-stimulating factor. In similar cultures initiated with CD34+CD38− cells from CML blood samples in which all of the LTC-IC were leukemic (Ph+), Ph+ LTC-IC activity was rapidly lost both in the presence and absence of admixed CD34+CD38− cells isolated from normal marrow. Conversely, the ability of normal LTC-IC to expand their numbers was shown to be independent of the presence of Ph+LTC-IC and later types of Ph+colony-forming cell (CFC) progenitors. In contrast to the LTC-IC, CFC were consistently -a m p l i f i e d i n c u l t u r e s i n i t i a t e d w i t h C M L - d e r i v e d -CD34+CD38− cells and the additional CFC present after 10 days were, like the starting population of CFC, almost exclusively Ph+ regardless of the genotype(s) of the LTC-IC in the original CML samples. Amplification of the Ph+CFC population in these cultures showed the same factor dependence as previously demonstrated for the in vitro expansion of CFC from normal marrow CD34+CD38− cells. Ph+LTC-IC disappeared regardless of the cytokines present. Taken together these findings support a model of CML in which the leukemic stem cells are characterized by a decreased probability of self-renewal and an increased probability of differentiation. In addition, they suggest new opportunities for improving the treatment of CML using strategies that require autologous stem cell rescue.
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Petzer, A. L., C. J. Eaves, M. J. Barnett und A. C. Eaves. „Selective Expansion of Primitive Normal Hematopoietic Cells in Cytokine-Supplemented Cultures of Purified Cells From Patients With Chronic Myeloid Leukemia“. Blood 90, Nr. 1 (01.07.1997): 64–69. http://dx.doi.org/10.1182/blood.v90.1.64.64_64_69.
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We have previously reported that primitive normal hematopoietic cells detectable as long-term culture-initiating cells (Ph-LTC-IC) are present at high levels in the blood of some patients with chronic myeloid leukemia (CML). We now show that this population can be expanded several-fold when highly purified CD34+CD38− cells isolated from the blood of such patients are cultured for 10 days in a serum-free medium containing 100 ng/mL of Flt3-ligand and Steel factor and 20 ng/mL of interleukin-3 (IL-3) and IL-6, and granulocyte colony-stimulating factor. In similar cultures initiated with CD34+CD38− cells from CML blood samples in which all of the LTC-IC were leukemic (Ph+), Ph+ LTC-IC activity was rapidly lost both in the presence and absence of admixed CD34+CD38− cells isolated from normal marrow. Conversely, the ability of normal LTC-IC to expand their numbers was shown to be independent of the presence of Ph+LTC-IC and later types of Ph+colony-forming cell (CFC) progenitors. In contrast to the LTC-IC, CFC were consistently -a m p l i f i e d i n c u l t u r e s i n i t i a t e d w i t h C M L - d e r i v e d -CD34+CD38− cells and the additional CFC present after 10 days were, like the starting population of CFC, almost exclusively Ph+ regardless of the genotype(s) of the LTC-IC in the original CML samples. Amplification of the Ph+CFC population in these cultures showed the same factor dependence as previously demonstrated for the in vitro expansion of CFC from normal marrow CD34+CD38− cells. Ph+LTC-IC disappeared regardless of the cytokines present. Taken together these findings support a model of CML in which the leukemic stem cells are characterized by a decreased probability of self-renewal and an increased probability of differentiation. In addition, they suggest new opportunities for improving the treatment of CML using strategies that require autologous stem cell rescue.
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Kuo, Chia-Ling, Ben Kirk, Meiruo Xiang, Luke C. Pilling, George A. Kuchel, Richard Kremer und Gustavo Duque. „Very Low and High Levels of Vitamin D Are Associated with Shorter Leukocyte Telomere Length in 148,321 UK Biobank Participants“. Nutrients 15, Nr. 6 (19.03.2023): 1474. http://dx.doi.org/10.3390/nu15061474.
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Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n = 148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Serum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β = −0.018, 95% CI −0.033 to −0.003, p = 0.022) and 0.048 SD (standardized β = −0.048, 95% CI −0.083 to −0.014, p = 0.006), respectively. Additionally, the high serum 25OHD groups (>95.9 nmol/L) had 0.038 SD (standardized β = −0.038, 95% CI −0.072 to −0.004, p = 0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusions: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Our findings could be affected by unmeasured confounders. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.
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Li, Junjun, Jingyu Yang, Bowei Xu, Yongsheng Yang, Furong Wen und Haitao Song. „Hybrid Scheduling for Multi-Equipment at U-Shape Trafficked Automated Terminal Based on Chaos Particle Swarm Optimization“. Journal of Marine Science and Engineering 9, Nr. 10 (01.10.2021): 1080. http://dx.doi.org/10.3390/jmse9101080.
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Aimed to improve the efficiency of port operations, Shanghai Zhenhua Heavy Industries Co., Ltd. (ZPMC) proposed a new U-shape trafficked automated terminal. The new U-shape trafficked automated terminal brings a new hybrid scheduling problem. A hybrid scheduling model for yard crane (YC), AGV and ET in the U-shape trafficked automated terminal yard is established to solve the problem. The AGV and ET yard lanes are assumed to be one-way lane. Take the YC, AGV and ET scheduling results (the container transportation sequences) as variables and the minimization of the maximum completion time as the objective function. A scheduling model architecture with hierarchical abstraction of scheduling objects is proposed to refine the problem. The total completion time is solved based on a static and dynamic mixed scheduling strategy. A chaotic particle swarm optimization algorithm with speed control (CCPSO) is proposed, which include a chaotic particle strategy, a particle iterative speed control strategy, and a particle mapping space for hybrid scheduling. The presented model and algorithm were applied to experiments with different numbers of containers and AGVs. The parameters of simulation part refer to Qinzhou Port. The simulation results show that CCPSO can obtain a near-optimal solution in a shorter time and find a better solution when the solution time is sufficient, comparing with the traditional particle swarm optimization algorithm, the adaptive particle swarm optimization algorithm and the random position particle swarm optimization algorithm.
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Selleri, C., JP Maciejewski, T. Sato und NS Young. „Interferon-gamma constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent hematopoietic inhibition“. Blood 87, Nr. 10 (15.05.1996): 4149–57. http://dx.doi.org/10.1182/blood.v87.10.4149.bloodjournal87104149.
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Clinical and laboratory studies have suggested involvement of interferon-gamma (IFN-gamma) in the pathophysiology of aplastic anemia. T cells from aplastic anemia (AA) patients secrete IFN-gamma in vitro, activated cytotoxic lymphocytes infiltrate aplastic bone marrow (BM), and IFN-gamma mRNA, not detected in normal BM, is present in BM from most AA patients. Many patients respond to immunosuppressive therapy with antithymocyte globulin and cyclosporine. Using long-term BM cultures (LTBMC) as a tissue culture model of hematopoiesis, we show that IFN-gamma is a potent inhibitor in the long-term culture- initiating cell (LTC-IC) assay, the best in vitro surrogate test for human hematopoietic stem cells, as well as of the output of committed progenitor cells (colony-forming unit-granulocyte-macrophage [CFU-GM] and burst-forming unit-erythroid [BFU-E]). In LTBMC, continuous addition of relatively high IFN-gamma concentrations (1,000 U/mL weekly or 200 U/mL every 2 days) was required for inhibition of secondary colony formation, a measure of LTC-IC number and clonogenicity. To mimick local production of IFN-gamma, human stromal cells were engineered by retroviral-mediated gene transfer to express a transduced IFN-gamma gene. IFN-gamma secreted by stromal cells was far more potent than exogenous IFN-gamma in its effects in the LTC-IC assay. For purified CD34+ cells culture in the presence of IFN-gamma stroma dramatically reduced secondary colony numbers as well as production of CFU-GM and BFU-E. Supernatants from these cultures contained only about 20 U/mL of IFN-gamma; this quantity of cytokine, when added to LTBMC, had little effect on hematopoiesis. The mechanism of hematopoietic suppression was related to the inhibition of cell cycle progression and induction of apoptosis of CD34+ cells. There was no apparent effect of local low-level IFN-gamma production on stromal cell function, as reflected in cell morphology, cell surface phenotype, or expression of hematopoietic growth factor genes. LTBMC with genetically altered stromal cells offers an in vitro model of immune suppression of hematopoiesis in AA and may be helpful in testing certain therapeutic modalities. We infer from our data that local production of low levels of inhibitory cytokine is sufficient to markedly inhibit hematopoiesis and to destroy stem cells and more mature progenitor cells.
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Hummel, W., K. Horne, T. R. Marsh und Janet H. Wood. „Line Formation in U Gem and T Leo“. International Astronomical Union Colloquium 158 (1996): 87–88. http://dx.doi.org/10.1017/s0252921100038318.
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We present 3-D LTE radiative transfer calculations [1] for H, He and Ca in accretion disks (AD) of dwarf novae in quiescence. The model disk is assumed to be in hydrostatic equilibrium vertically, and to rotate with Keplerian velocities. Calculated emission lines are fitted to phase-averaged, continuum-subtracted spectra of U Gem (Fig. 1) and T Leo (Fig. 2). Up to four parameters of the AD have been fitted: distance D, baryonic number density N, isotropic turbulence Vtu and disk temperature T; the latter two are assumed to be constant throughout the disk. Geometrical parameters are from [2] and [3].
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VanScoy, Brian D., Elizabeth A. Lakota, Sujata M. Bhavnani, Greg Giesel, Ana I. Carranco, Yu Nagira, Shohei Ouchi, Kenichiro Kondo und Paul G. Ambrose. „1379. Determination of the Arbekacin Exposure Required to Prevent Amplification of Resistant Subpopulations Using Patient Pharmacokinetics Simulated in a Hollow-Fiber Infection Model (HFIM)“. Open Forum Infectious Diseases 5, suppl_1 (November 2018): S422—S423. http://dx.doi.org/10.1093/ofid/ofy210.1210.
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Abstract Background ME1100 (arbekacin inhalational solution) is an aminoglycoside in clinical development for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively). Due to the increase in resistance of Staphylococcus aureus and Pseudomonas aeruginosa to many antimicrobial agents, it is important to understand the relationships between amplification of drug resistance and each of drug exposure and therapy duration. The objective of the studies described herein was to utilize the HFIM to determine the arbekacin exposure after ME1100 administration required to prevent the emergence of drug-resistant subpopulations. Methods Duplicate 10-day HFIM assays were completed in which arbekacin total-drug epithelial lining fluid (ELF) concentration–time profiles following inhalational administration of ME1100 every 12 hours were simulated. Four isolates, two methicillin-resistant S. aureus (Arbekacin MIC = 1 mg/L), and two P. aeruginosa (Arbekacin MIC = 4 mg/L), were exposed to total-drug ELF area under the concentration–time curve (AUC) values ranging from 217 to 25,053 mg hour/L, which were simulated using two different half-lives, 1 hour (α) and 6.93 hours (β). The initial bacterial burden was 1.0 × 108 CFU/mL. Samples were collected for enumeration of both the total and drug-resistant bacterial burdens and evaluation of pharmacokinetic samples using LC/MS–MS. Results Total-drug ELF AUC:MIC ratios required to prevent amplification of MRSA and P. aeruginosa resistance in the HFIM over 10 days were 1,512 and 2,942, respectively. The higher AUC:MIC ratio required to prevent resistance for P. aeruginosa was most likely due to the presence of a small colony variant population. The relationship between total-drug ELF AUC:MIC ratio and change in log10 CFU from baseline of the drug-resistant sub-populations found on agar plates on Day 10 took the form of an inverted-U for three pathogens and a step-function for one (Figure 1). Conclusion These data, which address the goal of considering arbekacin exposures that prevent the development of on-therapy resistance in a clinical setting, will help to provide guidance for future ME1100 dose selection for the treatment of patients with HABP/VABP. Disclosures B. D. VanScoy, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support. E. A. Lakota, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support. S. M. Bhavnani, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support. G. Giesel, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support. A. I. Carranco, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support. Y. Nagira, Meiji Seika Pharma Co. Ltd.: Employee, Salary. S. Ouchi, Meiji Seika Pharma Co. Ltd.: Employee, Salary. K. Kondo, Meiji Seika Pharma Co. Ltd.: Employee, Salary. P. G. Ambrose, Meiji Seika Pharma Co. Ltd.: Research Contractor, Research support.
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Fujii, T., K. Murata, H. Onizawa, A. Onishi, K. Murakami, M. Tanaka, W. Yamamoto et al. „OP0190 A MACHINE LEARNING MODEL THAT PREDICTS RA PROGRESSION FROM UNDIFFERENTIATED ARTHRITIS -KURAMA AND ANSWER COHORT STUDY-“. Annals of the Rheumatic Diseases 82, Suppl 1 (30.05.2023): 126. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1476.
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BackgroundEarly diagnosis and treatment of rheumatoid arthritis (RA) improve clinical outcomes. Undifferentiated arthritis (UA) is arthritis that does not fit a specific diagnosis. Half of the UA undergo spontaneous remission, while 30% of cases develop RA. Therefore, in UA, identifying patients at high risk for developing RA and providing close monitoring for those patients is required for early diagnosis and treatment[1]). However, predicting the evolution of UA to RA is still difficult.ObjectivesMachine learning, including deep learning, which is comparable to and in some cases surpasses the performance of human experts, is broadening its application in medicine. This study aims to build a machine-learning model that predicts the development of UA to RA.MethodsFor model training, a total of 322 UA patients in KURAMA cohort were analyzed (Table 1). For variables to train models, we chose 24 clinical features, which are easy to obtain in daily clinical practice. The target variable was the final diagnosis. We built models using Random forest (RF), XGBoost (XGB), Logistic regression (LR), and Deep neural network (DNN) and compared their performances. For model validation, we used data of 88 UA cases in ANSWER cohort (Table 1).ResultsWe trained models using 24 clinical parameters at the first clinical visit, performed 10-fold cross-validation, and evaluated model performance by averaging accuracy and AUC. The performance of the models was 73.5%, 74.2%, 74.5%, and 85.1% in precision and 0.760, 0.734, 0.748, and 0.895 in AUC for RF, XGB, LR, and DNN, respectively. DNN showed the highest performance. We then applied the DNN model to external validation data from ANSWER cohort and found that the prediction accuracy was 80.0%.ConclusionUsing parameters available in clinical practice, we developed a DNN model that effectively predicted RA development in internal and external UA datasets. Applying a machine learning approach might enable identifying patients at high risk of RA progression and improve the clinical management of UA patients.Reference[1] de la Calle-Fabregat C, Niemantsverdriet E, Cañete JD, Li T, van der Helm-van Mil AHM, Rodríguez-Ubreva J, Ballestar E. Prediction of the Progression of Undifferentiated Arthritis to Rheumatoid Arthritis Using DNA Methylation Profiling. Arthritis Rheumatol. 2021 Dec;73(12):2229-2239. doi: 10.1002/art.41885. Epub 2021 Nov 2. PMID: 34105306.Table 1.Baseline patients’ characteristicsKURAMAANSWERVariablesRA (n=94)Non-RA (n=228)RA (n=14)Non-RA (n=74)age(median, yr)60 [46.5-69]53.5 [44-64]44 [37.75-53.5]63 [53.3-69.8]sex(female%)72.34%78.07%71.43%64.86%BMI(median, kg/m2)22.03 [20.09-24.29]21.23 [19.22-23.90]22.60 [20.85-28.37]21.55 [19.68-23.44]Family history of RA(positive %)31.91%27.19%14.29%17.57%Smoking(current or past %)35.11%30.70%57.14%63.51%CRP(median, mg/dL)0.3 [0.1-1.1]0.1 [0-0.1]0.23 [0.078-0.63]0.12 [0.04-1.09]ESR_1h(median, mm)19 [9-41]12 [6-19.25]11 [8-36.75]13 [7.5-37.5]RF(median, IU/mL)8 [8-22.7]8 [8-18.53]6 [5-36.75]7 [5-19]ACPA(median, U/mL)0.6 [0.6-0.7]0.6 [0.6-0.6]5.6 [0.675-263]0.7 [0.5-3.05]MMP-3(median, ng/mL)65.85 [43.15-137.58]46.7 [31.9-62.13]81.4 [49.03-98.78]55.35 [39.16-128.15]Dr_VAS(median, mm)20 [9.25-33]7 [2-17.25]20 [10.5-32.25]18 [10-33]Pt_VAS(median, mm)49.5 [22.25-67.75]44 [15-55.25]48.5 [31.5-64.5]47 [21-68]DAS28_CRP(median,)3.22 [2.36-4.08]2.38 [1.78-2.94]3.27 [2.38-4.02]3.09 [2.27-4.20]HAQ(median)0.5 [0.125-1]0.25 [0-0.5]0.313 [0-0.594]0.375 [0.125-0.969]ACR2010_points(median)4 [3-5]3 [2-4]1 [0.25-2.75]1 [0-2][Q1-Q3]AcknowledgementsI have no acknowledgments to declare.Disclosure of InterestsTakayuki Fujii Speakers bureau: Asahi Kasei Pharma, Abbvie, Jansen, Tanabe Mitsubishi Pharma, and Eisai., Koichi Murata Speakers bureau: AbbVie GK; Eisai Co., Ltd., Chugai.Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; Pfizer Inc.; Bristol-Myers Squibb;Asahi Kasei Pharma Corp., Hideo Onizawa Speakers bureau: AbbVie, Asahi Kasei, Astellas Pharma Inc.,Eisai Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and Daiichi.Sankyo Co. Ltd., Akira Onishi Speakers bureau: Pfizer Inc., Bristol-Myers Squibb., Advantest,Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Ono Pharmaceutical.Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., Abbvie Inc., Takeda.Pharmaceutical Co. Ltd., and Daiichi Sankyo Co. Ltd., Kosaku Murakami Speakers bureau: Eisai Co. Ltd, Chugai.Pharmaceutical Co. Ltd., Pfizer Inc., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation,UCB Japan Co. Ltd, Daiichi Sankyo Co. Ltd., and Astellas Pharma Inc., Masao Tanaka Speakers bureau: AbbVie GK, Asahi Kasei Pharma.Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai.Co., Ltd., Eli Lilly and Company, Pfizer Inc., UCB Japan Co., Ltd., Janssen Pharmaceutical K.K.,Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Pharma Co., Ltd, and Teijin.Pharma, Ltd., Wataru Yamamoto: None declared, Koji Nagai: None declared, Ayaka Yoshikawa: None declared, Yuki Etani: None declared, Yasutaka Okita Speakers bureau: Chugai Pharmaceutical, Pfizer, and Ono Pharmaceutical., Naofumi Yoshida: None declared, Hideki Amuro: None declared, Tadashi Okano Speakers bureau: Abbvie, Chugai, Eli Lilly, Janssen and Novartis Pharma., Grant/research support from: Abbvie, Asahi Kasei, Chugai, Eisai,Eli Lilly and Tanabe Mitsubishi., Yo Ueda: None declared, Ryota Hara Speakers bureau: AbbVie, Eisai, Motomu Hashimoto Speakers bureau: Abbvie, Asahi Kasei, Astellas, Ayumi, Bristol.Meyers, Chugai, EA Pharma, Eisai, Daiichi Sankyo, Eli Lilly, Nihon Shinyaku, Novartis Pharma,Tanabe Mitsubishi., Takaichi Okano: None declared, Akio Morinobu Speakers bureau: AbbVie G.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan.K.K., Eisai Co. Ltd., Pfizer Inc., Bristol-Myers Squibb., Mitsubishi Tanabe Pharma Co., Astellas.Pharma Inc., and Gilead Sciences Japan, Grant/research support from: AbbVie G.K., Asahi.Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co. and Eisai Co. Ltd., Shuichi Matsuda Speakers bureau: Astellas Pharma Inc., Daiichi Sankyo Co.Ltd., Mitsubishi Tanabe Pharma Corporation, Eisai Co., Ltd., Takeda Pharmaceutical Company Limited,Chugai Pharmaceutical Co. Ltd, Pfizer Inc., and Asahi Kasei Corporation.
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Chaib, Latifa, Abdelhak Ait Lahna, Hassan Admou, Nasrrddine Youbi, Warda El Moume, Colombo Celso Gaeta Tassinari, João Mata et al. „Geochemistry and Geochronology of the Neoproterozoic Backarc Basin Khzama Ophiolite (Anti-Atlas Mountains, Morocco): Tectonomagmatic Implications“. Minerals 11, Nr. 1 (09.01.2021): 56. http://dx.doi.org/10.3390/min11010056.
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The Khzama ophiolite is a highly dismembered complex located in the Siroua inlier of the Moroccan Anti-Atlas Belt. It consists of ultramafic rocks, cumulate gabbros, sheeted dikes, pillow lavas, and an overlying volcano-sedimentary sequence. Three main tectonic slices of sheeted dike complexes are studied in detail along three rivers, exposing well preserved outcrops where individual dikes are clearly distinguishable from the intruded host rock (Assif n’Tinzla, Assif n’Tasriwine, and Assif n’Iriri). Sheeted dikes of the Khzama ophiolitic complex are basaltic to andesitic in composition, displaying a clear sub-alkaline nature. We identify two sets of dikes that originate from lower High-Ti series (HTS) lavas and overlying upper Low-Ti series (LTS) lava. The immobile trace-element signatures of these rocks point to a genesis on a backarc environment with magmas sourced in a supra-subduction zone (SSZ) at the spinel peridotite zone. The obtained SHRIMP U-Pb data of the gabbro represent the first radiometric age of zircon extracted from the mafic rocks that were intruded by the sheeted dike complex of the Khzama ophiolite. These grains yield a concordia age of 763 ± 5 Ma, which is consistent with the 761.1 + 1.9/−1.6 and 762 + 1/−2 Ma U-Pb zircon ages of plagiogranites of Siroua. Based on their mineralogy, modal proportions, and major element chemistry, the felsic dikes are classified as high silica–low alumina trondhjemites or plagiogranites. These plagiogranites were likely formed by the partial melting of mafic rocks rather than by extreme fractional crystallization. A plagiogranite dated at 777 ± 4.7 Ma (U-Pb on zircon) is significantly older than the ca. 762 Ma plagiogranites previously recorded for the Khzama locality, suggesting a long-lived supra-subduction zone (SSZ) with conditions for the hydrous melting of mafic rocks.
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Chaib, Latifa, Abdelhak Ait Lahna, Hassan Admou, Nasrrddine Youbi, Warda El Moume, Colombo Celso Gaeta Tassinari, João Mata et al. „Geochemistry and Geochronology of the Neoproterozoic Backarc Basin Khzama Ophiolite (Anti-Atlas Mountains, Morocco): Tectonomagmatic Implications“. Minerals 11, Nr. 1 (09.01.2021): 56. http://dx.doi.org/10.3390/min11010056.
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The Khzama ophiolite is a highly dismembered complex located in the Siroua inlier of the Moroccan Anti-Atlas Belt. It consists of ultramafic rocks, cumulate gabbros, sheeted dikes, pillow lavas, and an overlying volcano-sedimentary sequence. Three main tectonic slices of sheeted dike complexes are studied in detail along three rivers, exposing well preserved outcrops where individual dikes are clearly distinguishable from the intruded host rock (Assif n’Tinzla, Assif n’Tasriwine, and Assif n’Iriri). Sheeted dikes of the Khzama ophiolitic complex are basaltic to andesitic in composition, displaying a clear sub-alkaline nature. We identify two sets of dikes that originate from lower High-Ti series (HTS) lavas and overlying upper Low-Ti series (LTS) lava. The immobile trace-element signatures of these rocks point to a genesis on a backarc environment with magmas sourced in a supra-subduction zone (SSZ) at the spinel peridotite zone. The obtained SHRIMP U-Pb data of the gabbro represent the first radiometric age of zircon extracted from the mafic rocks that were intruded by the sheeted dike complex of the Khzama ophiolite. These grains yield a concordia age of 763 ± 5 Ma, which is consistent with the 761.1 + 1.9/−1.6 and 762 + 1/−2 Ma U-Pb zircon ages of plagiogranites of Siroua. Based on their mineralogy, modal proportions, and major element chemistry, the felsic dikes are classified as high silica–low alumina trondhjemites or plagiogranites. These plagiogranites were likely formed by the partial melting of mafic rocks rather than by extreme fractional crystallization. A plagiogranite dated at 777 ± 4.7 Ma (U-Pb on zircon) is significantly older than the ca. 762 Ma plagiogranites previously recorded for the Khzama locality, suggesting a long-lived supra-subduction zone (SSZ) with conditions for the hydrous melting of mafic rocks.
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Yim, Seongjin, und Wongun Kim. „Rollover Prevention Control for Autonomous Electric Road Sweeper“. Electronics 10, Nr. 22 (14.11.2021): 2790. http://dx.doi.org/10.3390/electronics10222790.
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This paper presents a method to prevent the rollover of autonomous electric road sweepers (AERS). AERS have an articulated frame steering (AFS) mechanism. Moreover, the heights of the center of gravity of the front and rear bodies are high. As such, they are prone to rolling over at low speeds and at small articulation angles. A bicycle model with a nonlinear tire model was used as a vehicle model for AERS. Using that vehicle model, path tracking and speed controllers were designed in order to follow a predefined path and speed profile, respectively. To check the rollover propensity of AERS, load transfer ratio (LTR) based the rollover analysis was completed. Based on the results of the analysis, a rollover prevention scheme was proposed. To validate the proposed scheme, a simulation was conducted using a U-shaped path under constant speed conditions. From the simulation, it was shown that the proposed scheme is effective in preventing AERS from rolling over.
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Chen, Nianhang, Abderrahmane Laadem, Dawn M. Wilson, Xiaosha Zhang, Matthew L. Sherman, Steve Ritland und Kenneth M. Attie. „Pharmacokinetics and Exposure-Response of Luspatercept in Patients with Anemia Due to Low- or Intermediate-1-Risk Myelodysplastic Syndromes (MDS): Preliminary Results from Phase 2 Studies“. Blood 128, Nr. 22 (02.12.2016): 1990. http://dx.doi.org/10.1182/blood.v128.22.1990.1990.
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Abstract Background: Luspatercept is a modified ActRIIB-IgG Fc fusion protein that corrects ineffective erythropoiesis. In phase 2 studies, luspatercept treatment led to long-term increases in hemoglobin (Hb) levels and reduction in transfusion burden in patients (pts) with IPSS Low- or Intermediate-1-risk MDS. Aims: To characterize the pharmacokinetics (PK) of luspatercept and explore the exposure-response relationship for efficacy and safety in pts with MDS, thereby informing selection of the starting dose for phase 3 studies of luspatercept in MDS. Methods : PK, safety, and efficacy data were collected from two phase 2 studies (base and extension). In the base study, luspatercept was administered once every 3 weeks by subcutaneous injection to sequential cohorts for up to 5 doses. The base study included a dose-finding phase (at fixed doses from 0.125 to 1.75 mg/kg), and an expansion cohort (at a starting dose of 1.0 mg/kg followed by individual dose titration up to 1.75 mg/kg). Pts completing the base study were eligible to enroll in an extension study, where they continued to receive luspatercept every 3 weeks for up to 24 months. Pts who had treatment interruption for ≥ 3 months before enrolling in the extension study received a starting dose of 1.0 mg/kg (followed by dose titration) and were treated as "new" pts in the exposure-response analysis. The main exposure endpoint was area under the luspatercept serum concentration−time curve (AUC). Clinical endpoints included Hb increase, transfusion reduction, and drug-related adverse events (AEs) in weeks 1-15. Responders were defined as pts achieving erythroid hematologic improvement (HI-E) per IWG criteria, i.e. Hb increase ≥ 1.5 g/dL for 8 weeks in low transfusion burden (LTB) pts, and transfusion reduction ≥ 4 RBC units/8 weeks in high transfusion burden (HTB) pts. Results : As of July 20, 2016, preliminary data were available for 66 pts: 22 LTB pts (baseline Hb 6.4-10.1 g/dL) and 44 HTB pts (baseline transfusion burden 4-18 units/8 weeks). Median age was 72 years (range 27-90); 41% were female. A total of 39 pts were eligible for individual dose titration; of these, ~49% had ≥ 1 dose escalation (to 1.33 mg/kg) and ~15% had 2 dose escalations (to 1.75 mg/kg) in the first 3 months. Luspatercept PK was adequately described by a 1-compartment PK model with linear absorption and elimination. Half-life of luspatercept in serum was ~10-14 days across doses. Body weight positively correlated with luspatercept clearance and its volume of distribution. Baseline transfusion burden (LTB vs HTB) and erythropoietin (EPO) level (10-4,752 U/L) had no significant effect on luspatercept PK. In LTB pts who were transfusion-free on treatment, higher luspatercept AUC correlated with greater Hb increase (P < 0.01). In HTB pts, AUC correlated with reduced transfusion units in pts with baseline EPO ≤ 500 U/L (P< 0.01) but not in pts with baseline EPO > 500 U/L. Median AUC was 148 d·µg/mL in LTB responders and 185 d·µg/mL in HTB responders. Luspatercept AUC also correlated with frequency of IWG HI-E responders for LTB pts, HTB pts (baseline EPO ≤ 500 U/L), and the 2 groups combined. In pts requiring transfusion (≥ 2 units/8 weeks) with baseline EPO ≤ 500 U/L, baseline transfusion burden was a significant predictor of achieving transfusion independence (TI) ≥ 8 weeks, and higher luspatercept AUC was associated with greater TI rate after accounting for baseline transfusion burden. Thus, individualized dosing based on baseline transfusion burden may increase the likelihood of achieving TI in HTB pts. Population PK simulation predicted that the starting dose resulting in 90% of LTB pts and 50% of HTB pts achieving efficacious AUC for HI-E would be 1 mg/kg and 1.1 mg/kg, respectively; higher doses would result in a higher proportion of pts achieving efficacious AUC. There was no significant relationship between severity and frequency of drug-related AEs and luspatercept serum exposure. Conclusions: Higher luspatercept serum exposure correlated with greater erythroid hematopoietic response for both LTB and HTB pts. Exposure-response modeling and PK simulation support a phase 3 starting dose of 1.0 mg/kg and intra-patient dose escalation up to 1.75 mg/kg according to erythroid hematopoietic response. A phase 3 study of luspatercept in regularly transfused ring sideroblast positive patients with lower-risk MDS according to IPSS-R criteria is ongoing (MEDALIST study; ClinicalTrials.gov NCT02631070). Disclosures Chen: Celgene Corporation: Employment, Equity Ownership. Laadem:Celgene Corporation: Employment, Equity Ownership. Wilson:Acceleron Pharma: Employment, Equity Ownership. Zhang:Acceleron Pharma: Employment. Sherman:Acceleron Pharma: Employment, Equity Ownership, Patents & Royalties. Ritland:Celgene Corporation: Employment, Equity Ownership. Attie:Acceleron Pharma: Employment, Equity Ownership.
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Misaki, K., E. Tanaka, E. Inoue, K. Tsuritani, S. Matsumoto, H. Yamanaka und M. Harigai. „POS0603 ANALYSIS OF FACTORS ASSOCIATED WITH THE EFFECTIVENESS OF ABATACEPT IN THE ORIGAMI STUDY“. Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 536. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1028.
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Background:The ORIGAMI study is a multicenter, observational study to evaluate the effectiveness, safety, and patient-reported outcomes of abatacept (ABA) in Japanese patients with csDMARD-resistant, Simplified Disease Activity Index (SDAI)-moderate, biologic-naïve rheumatoid arthritis (RA). ABA has shown better effectiveness/efficacy in RA patients with anti-cyclic citrullinated peptide antibody (ACPA) positive (1) and high ACPA titer (2) compared to ACPA negative and low ACPA titer, respectively. However, more accurate predictors of effectiveness in clinical practice are needed than ACPA status.Objectives:This post-hoc analysis is aimed to determine the association between ACPA and ABA effectiveness (disease activity and physical function) or retention rate and to investigate other factors associated with the effectiveness of ABA in patients enrolled in the ORIGAMI study.Methods:Of the 279 patients in the effectiveness analysis set of the ORIGAMI study, 270 patients with baseline ACPA measurement were analyzed. The patients were divided into the ACPA-positive group (ACPA +ve, ≥4.5 U/mL at baseline) and the ACPA-negative group (ACPA –ve, <4.5 U/mL). Patients’ characteristics, changes in disease activity and physical function (Japanese Health Assessment Questionnaire; J-HAQ) through 52 weeks, and retention rates of ABA at week 52 were evaluated. Baseline characteristics and use of concomitant drugs were analyzed as independent variables by multiple regression analysis using a standard linear model adjusted by SDAI at week 0 to identify factors associated with SDAI change at week 52. In addition, the interaction effects among ACPA status, RF status, and the factor that was significantly associated with SDAI change in multiple regression analysis on changes in SDAI were explored.Results:The numbers of ACPA +ve and –ve patients were 226 and 44, respectively. ACPA values (mean ± SD, U/mL) were 280.3 ± 376.8 and 0.9 ± 0.7, and rheumatoid factor (RF) values were 174.8 ± 302.6 and 20.9 ± 61.7 in the ACPA +ve and –ve groups, respectively. Mean (95% confidence interval) changes in SDAI at week 52 were −11.3 (−12.4 to −10.3) and −8.0 (−10.5 to −5.5), and those in J-HAQ were −0.27 (−0.34 to −0.20) and −0.16 (−0.34 to 0.01) in the ACPA +ve and –ve groups, respectively. In the Kaplan–Meier analysis, the retention rates of ABA at week 52 in the ACPA +ve and –ve groups were 72.1% and 58.7%, (discontinuation for any reason), and 91.6% and 75.7% (discontinuation because of lack of effectiveness), respectively. In a multiple regression analysis, the duration of disease (< 1 year) was associated with the change in SDAI at week 52. With respect to SDAI changes, the estimated difference of ACPA +ve and disease duration (< 1 year), ACPA +ve and disease duration (≥1 year), and ACPA –ve and disease duration (< 1 year), versus ACPA −ve and disease duration (≥ 1 year), were −4.26 (p = 0.022), −0.82 (p = 0.618), and −0.93 (p = 0.716), respectively (Fig. 1). The estimated difference of ACPA +ve and RF +ve, ACPA +ve and RF –ve, and ACPA –ve and RF +ve, versus ACPA –ve and RF –ve, were −2.48 (p = 0.060), −2.77 (p = 0.107), and −5.48 (p = 0.087), respectively.Conclusion:A higher retention rate as well as better effectiveness of ABA on disease activity and physical function in ACPA +ve group versus ACPA –ve group were shown in the simple subgroup analysis. ABA effectiveness on the SDAI change was significantly better in patients with disease duration <1 year and ACPA +ve compared to those with ACPA −ve and disease duration ≥ 1 year.References:[1]Harrold LR et al. J Rheumatol 2018;45(1):32–39.[2]Sokolove J et al. Ann Rheum Dis 2016;75(4):709–714.Disclosure of Interests:Kenta Misaki Speakers bureau: Eisai Co., Ltd., AbbVie GK, Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Grant/research support from: Ono Pharmaceutical Co., Ltd., Eiichi Tanaka Speakers bureau: AbbVie GK, Asahi Kasei Pharma Corporation, Astellas Pharma Inc, Ayumi Pharmaceutical Corporation, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Pfizer, Takeda Pharmaceutical Co., Ltd, and Teijin Pharma Ltd., Eisuke Inoue Speakers bureau: Pfizer Japan, Bristol-Myers Squibb K.K., Katsuki Tsuritani Employee of: Bristol-Myers Squibb K.K., Shigeru Matsumoto Employee of: Ono Pharmaceutical Co., Ltd., Hisashi Yamanaka Consultant of: Bristol-Myers Squibb K.K., masayoshi harigai Speakers bureau: AbbVie GK, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Consultant of: AbbVie GK, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Gilead Sciences Inc., Grant/research support from: AbbVie GK, and Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd. Daiichi-Sankyo, Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Nippon Kayaku Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.
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Hesselink, Wim H. „UNITY and Büchi automata“. Formal Aspects of Computing 33, Nr. 2 (10.02.2021): 185–205. http://dx.doi.org/10.1007/s00165-020-00528-x.
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AbstractUNITY is a model for concurrent specifications with a complete logic for proving progress properties of the form “P leads to Q”. UNITY is generalized to U-specifications by giving more freedom to specify the steps that are to be taken infinitely often. In particular, these steps can correspond to non-total relations. The generalization keeps the logic sound and complete. The paper exploits the generalization in two ways. Firstly, the logic remains sound when the specification is extended with hypotheses of the form “F leads to G”. As the paper shows, this can make the logic incomplete. The generalization is used to show that the logic remains complete, if the added hypotheses “F leads to G” satisfy “F unless G”. The main result extends the applicability and completeness of UNITY logic to proofs that a given concurrent program satisfies any given formula of LTL, linear temporal logic, without the next-operator which is omitted because it is sensitive to stuttering. For this purpose, the program, written as a UNITY program, is extended with a number of boolean variables. The proof method relies on implementing the LTL formula, i.e., restricting the specification in such a way that only those runs remain that satisfy the formula. This result is a variation of the classical construction of a Büchi automatonfor a given LTL formula that accepts precisely those runs that satisfy the formula.
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Imanishi, Masatoshi, Shunsuke Baba, Kouichiro Nakanishi und Takuma Izumi. „Dense Molecular Gas Properties of the Central Kiloparsec of Nearby Ultraluminous Infrared Galaxies Constrained by ALMA Three Transition-line Observations“. Astrophysical Journal 950, Nr. 1 (01.06.2023): 75. http://dx.doi.org/10.3847/1538-4357/acc388.
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Abstract We report the results of Atacama Large Millimeter/submillimeter Array (ALMA) 1–2 kpc resolution, three rotational transition-line (J = 2–1, J = 3–2, and J = 4–3) observations of multiple dense molecular gas tracers (HCN, HCO+, and HNC) for 10 nearby (ultra)luminous infrared galaxies ((U)LIRGs). Following the matching of beam sizes to 1–2 kpc for each (U)LIRG, the high-J-to-low-J transition-line flux ratios of each molecule and the emission-line flux ratios of different molecules at each J transition are derived. We conduct RADEX non-LTE model calculations and find that, under a wide range of gas density and kinetic temperature, the observed HCN-to-HCO+ flux ratios in the overall (U)LIRGs are naturally reproduced with enhanced HCN abundance compared to HCO+. Thereafter, molecular gas properties are constrained primarily through the use of HCN and HCO+ data and the adoption of fiducial values for the HCO+ column density and HCN-to-HCO+ abundance ratio. We quantitatively confirm the following: (i) molecular gas at the (U)LIRGs’ nuclei is dense (≳103–4 cm−3) and warm (≳100 K), (ii) the molecular gas density and temperature in nine ULIRGs’ nuclei are significantly higher than those of one LIRG’s nucleus, (iii) molecular gas in starburst-dominated sources tends to be less dense and cooler than ULIRGs with luminous AGN signatures. For six selected sources, we also apply a Bayesian approach by freeing all parameters and support the above main results. Our ALMA 1–2 kpc resolution, multiple transition-line data of multiple molecules are a very powerful tool for scrutinizing the properties of molecular gas concentrated around luminous energy sources in nearby (U)LIRGs’ nuclei.
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Ogiwara, Kenichi, Hiroki Horiuchi, Keiji Nogami, Takehisa Kitazawa und Midori Shima. „Assessment of Emicizumab-Driven Clot Stability in Hemophilia a Model“. Blood 132, Supplement 1 (29.11.2018): 2478. http://dx.doi.org/10.1182/blood-2018-99-118379.
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Abstract Clot stability is an important hemostatic aspect in treating patients with hemophilia A (HA). Effects of factor VIII (FVIII), recombinant activated FVII (rFVIIa), FXIII and tranexamic acid on clot stability in hemophilia had been reported1). Emicizumab (Emi), FVIIIa-mimicking bispecific antibody, is a recently approved novel therapeutics for HA with inhibitor. Although hemostatic activity of Emi was confirmed by preclinical and clinical studies, whether Emi-driven clot stability is similar to that of FVIII or not remains unknown. Furthermore, in clinical trial of Emi, thrombotic events were reported when high doses of activated prothrombin complex concentrates (aPCC) were used concurrently with Emi. Effect of aPCC on clot stability and its possible association with the thrombotic events should be also clarified. In this study, we investigated the effect of Emi on clot stability with a thromboelastometry (ROTEM) -based assay using tissue plasminogen activator (tPA) as a fibrinolysis trigger, and compared it with that of FVIII or bypassing agents (BPAs). Furthermore, we assessed the effect of BPAs on Emi-driven clot stability. Normal blood from healthy volunteer (n=22) was incubated with anti-FVIII antibody (FVIII:C <1 IU/dL), which was regarded as HA model blood. HA model blood was spiked with Emi (50 μg/ml), rFVIIa (22 nM), and aPCC (1 U/ml). ROTEM was performed with/without tPA (2 nM). We used ellagic acid (Elg, x300 INTEM®) as a trigger in addition to tissue factor (TF, 0.5 pM) since TF-trigger was not sensitive to Emi. Residual area under the curve in 30 min (%AR30) was used as a clot stability parameter. Median values (25-75%tile) of %AR30 were compared among the groups with Dunn's multiple comparison test [*p<0.05, **p<0.01, ***p<0.001]. In Elg-trigger ROTEM, %AR30 of HA model blood had no values since coagulation did not occur within test time. However, coagulation was improved in HA model spiked with Emi and its clot stability showed slightly weak value with no statistical significance [50% (30-76), p>0.05] compared to normal blood [75% (56-90)]. Whilst, HA model + rFVIIa [13%*** (7-22)] and HA model + aPCC [41%*** (20-71)] showed significantly weak values, indicating that effect of Emi on clot stability was comparable to normal blood and better than BPAs in Elg trigger. Concomitant effect of Emi and BPAs were evaluated. Compared to HA model + Emi [50% (30-76)], clot stability increased in the co-presence of Emi and aPCC [99%*** (96-101)] but not in that of Emi and rFVIIa [53% (29-78)]. TF trigger, which was sensitive to BPAs but not to Emi, was also used in order to evaluate concomitant effect of Emi and BPAs. In TF trigger, clot stability of HA model blood + Emi [31% (19-47)] was similar to that of HA mode blood [27% (20-44)] or normal blood [32% (22-55)], but increased in HA model + rFVIIa [43%** (30-62)] and HA model + aPCC [41%** (29-68)]. rFVIIa increased clot stability of HA model blood in the presence of Emi [56%** (28-65)] more than its absence. Effect of the aPCC in the presence of Emi [87%*** (78-91)] was much more remarkable than that of rFVIIa. In conclusion, effect of Emi on clot stability in HA model blood was comparable to that of normal blood, indicating that clot formation under Emi had no qualitative difference with FVIII. Clot stability remarkably increased in Emi in the presence of aPCC, suggesting that hyper clot stability might be one of the reasons of thrombotic events in the concomitant use of Emi and aPCC. 1) Tran HT, et al. Tranexamic acid as adjunct therapy to bypassing agents in haemophilia A patients with inhibitors. Haemophilia. 2014 May;20(3):369-75. Disclosures Ogiwara: CSL Behring: Research Funding. Nogami:Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau. Kitazawa:Chugai Pharmaceutical Co., Ltd: Employment, Equity Ownership, Patents & Royalties: Patents related to emicizumab. Shima:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau.
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Jeong, Yonghwan, Wongun Kim und Seongjin Yim. „Model Predictive Control Based Path Tracking and Velocity Control with Rollover Prevention Function for Autonomous Electric Road Sweeper“. Energies 15, Nr. 3 (28.01.2022): 984. http://dx.doi.org/10.3390/en15030984.
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This paper presents a model predictive control (MPC)-based algorithm for rollover prevention of an autonomous electric road sweeper (AERS). For AERS, the basic function of autonomous driving is a path- and velocity-tracking control needed to make a vehicle follow given path and velocity profiles. On the other, the AERS adopts an articulated frame steering (AFS) mechanism which can make cornering behavior agile. Moreover, the tread of the AERS is narrow, and the height of the mass center is high. As a result, it is prone to roll over. For this reason, it is necessary to design a controller for path and velocity tracking and rollover prevention in order to improve maneuverability and roll safety of the AERS. A kinematic model was adopted as a vehicle one for the AERS. With the vehicle model, reference states of position and velocity were determined that are needed to make the AERS track the reference path and prevent rollover. With the vehicle model and reference states, an MPC-based motion controller was designed to optimize articulation angle and velocity commands. The load-transfer ratio (LTR) was used to measure a rollover propensity. To evaluate the proposed algorithm, a simulation was conducted for the U-turn scenario. Simulation results show that the proposed algorithm improves path tracking and prevents the rollover of the AERS.
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Arai, Ayako, Masahide Yamamoto, Maho Sato, Yasushi Onishi, Yoji Sasahara, Hideki Sano, Masayoshi Masuko et al. „The Outcomes of Systemic Chronic Active EBV Infection Treatment By Allogeneic Hematopoietic Stem Cell Transplantation: An Analysis of Japanese Registry Data“. Blood 138, Supplement 1 (05.11.2021): 3965. http://dx.doi.org/10.1182/blood-2021-147046.
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Abstract Background and aims Systemic chronic active Epstein-Barr virus infection (sCAEBV) is classified as T- or NK-cell neoplasms in the WHO classification revised in 2017. Although allogeneic stem cell transplantation (allo-HSCT) is efficacious for sCAEBV, the effects are yet to be analyzed in a large number of cases due to the disease rarity. To investigate the outcomes and the prognostic factors of allo-HSCT in sCAEBV under the definition of the WHO 2017 classification, we analyzed retrospectively using the database of Japanese Society for Transplantation and Cellular Therapy (JSTCT). Methods Data collection We used the clinical data of hematopoietic stem cell transplantation (HSCT) recipients of the Transplant Registry Unified Management Program (TRUMP) sponsored by JSTCT and Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT). Patients who underwent HSCT to cure EBV-associated diseases, secondary hemophagocytic lymphohistiocytosis (HLH), and virus-associated hemophagocytic syndrome between January 1993 and December 2016 were selected in TRUMP database, and on our behalf, JDCHCT sent out survey questions to the institutions of these patients to collect additional data to check if the diagnosis of sCAEBV matches our criteria, to analyze disease status at the time of HSCT, and to evaluate the efficacy of different treatment methods. The diagnosis of sCAEBV sCAEBV was diagnosed according to criteria suggested in 2016 by the Research group of Measures against Intractable Diseases by Ministry of Health, Labour and Welfare of Japan: (1) elevated EBV DNA load in peripheral blood (PB) (> 10 2.5 copies/μg DNA), (2) detection of EBV infection in T or NK cells from the affected tissues or PB, (3) systemic inflammatory symptoms such as fever, lymphadenopathy, liver dysfunction, progressive skin lesions, vasculitis, and uveitis persisting for > 3 months, and (4) exclusion of other possible diseases, such as primary EBV infection, autoimmune disease, immunodeficiencies, and lymphomas. Patients who fulfilled all (1) to (4) were diagnosed as sCAEBV. These criteria are compatible with the definition of sCAEBV described in the WHO definition of 2017. The definitions of disease activities and responses The disease activities are defined in previous reports (Blood. 2012;119, p673 and BMT. 2016;51, p879) as follows: positive of fever, ALT level elevation, vasculitis, progressive skin lesions, or uveitis. We defined the complete resolution of disease activity as complete response (CR) and CR with a significant decrease in PB EBV-DNA load (< 10 2.5 copies/μg DNA) as virological CR (vCR). Results 81 patients who met the diagnostic criteria of sCAEBV were analyzed. The median age at HSCT was 24 years old, and the three-year overall survival rate (3-year OS) was 74.0%. Of 74 patients whose viral load after HSCT evaluated, 49 (66.2%) achieved vCR. The multivariate cox proportional hazard model revealed that advanced age, adolescent and young adult (AYA) (age, 15-39; n = 48) and adult (age, > 40; n = 13), was a risk factor of poor OS. The hazard ratios (HR) of AYA and adult groups were 10.14 and 4.63 respectively. It also showed that the presence of HLH at HSCT (HR 4.55), high sIL-2R (≥ median, 691 U/mL) at HSCT (HR 5.27), and conditioning without total body irradiation (HR 3.23) were independently associated with poor survival. Moreover, the median survival time of patients with active disease and extremely high sIL-2R level (≥ 3 × median, 2073 U/mL) was 0.9 months, whereas the other groups did not reach the median. Conclusion Although HSCT is the only curative treatment for sCAEBV, the strategies need improvements in high-risk cases, especially of high sIL-2R. Disclosures Arai: ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; Kyowa Kirin CO., LTD.: Honoraria, Research Funding; Abbvie: Honoraria; BMS: Honoraria; Elsai Co Ltd: Research Funding; Abbott Japan LLC: Honoraria; Nippon Shinyaku Co. Ltd: Honoraria, Research Funding; Otsuka Pharmaceuticals Co. Ltd: Research Funding; Novartis Pharma KK: Honoraria; Takeda Pharmaceuticals Co Ltd: Honoraria, Research Funding; Shionogi & Co Ltd: Research Funding; Asahi Kasri Pharma Corporation: Research Funding; Sanofi: Honoraria; Pfizer japan: Honoraria; Astellas Pharma Inc.: Honoraria. Yamamoto: Bristol-Myers Squibb Company: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Eisai Co., Ltd.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; NIPPON SINYAKU CO., LTD: Honoraria; Novartis Pharma: Honoraria; ONO PHARMACEUTICAL CO.: Honoraria; Otsuka Pharmaceutical: Honoraria; Pfizer Japan Inc.: Honoraria; Takeda: Honoraria. Nakamae: Astellas Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; Simon-Kucher & Partners: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Takeda Pharmaceutical Company Limited.: Honoraria; Novartis: Honoraria, Research Funding; Pfizer Japan Inc.: Honoraria; Bristol-Myers Squibb Company: Honoraria, Research Funding; Alexion: Research Funding; PPD-SNBL K.K: Research Funding; CMIC HOLDINGS Co., Ltd: Research Funding. Ichinohe: Repertoire Genesis Inc.: Honoraria, Research Funding; Novartis Pharma K.K.: Honoraria; Celgene: Honoraria; Zenyaku Kogyo Co.: Research Funding; Takara Bio Inc.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Honoraria, Research Funding; Otsuka Pharmaceutical Co.: Research Funding; Nippon Shinyaku Co: Research Funding; Ono Pharmaceutical Co.: Honoraria, Research Funding; Kyowa Kirin Co.: Honoraria, Research Funding; FUJIFILM Wako Chemicals.: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Eisai Co.: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Chugai Pharmaceutical: Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceutical Co.: Honoraria; AbbVie Pharma: Research Funding; Astellas Pharma: Honoraria, Research Funding. Atsuta: Astellas Pharma Inc.: Speakers Bureau; Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria.
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Yamaguchi, Kazuki, Tetsuhiro Soeda, Motohiko Sato, Norihito Shibahara, Hikaru Koga, Mina Ichiki, Eri Joyashiki et al. „Pharmacology and Pharmacokinetics of NXT007; Emicizumab-Based Engineered Fixa/Fx Bispecific Antibody with Improved Properties“. Blood 136, Supplement 1 (05.11.2020): 19. http://dx.doi.org/10.1182/blood-2020-138958.
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Background Emicizumab (HEMLIBRA®) is a factor (F) VIII function-mimetic therapeutic bispecific antibody (BsAb) to FIXa and FX able to prevent bleeding in persons with hemophilia A (PwHA) when injected subcutaneously once every 1, 2 or 4 weeks. To develop a next generation version, we sought an agent able to keep hemostatic potential in non-hemophilic range with more convenient dosing regimen (dosing frequency/volume). We successfully created the emicizumab-based engineered four-chain BsAbs, NXT series. Among these, we selected NXT007 as a clinical candidate. Objectives The aim of this study is to clarify the in vitro and in vivo properties of NXT007 and predict its therapeutic potency non-clinically. Methods We evaluated the pharmacological activities of NXT007 in vitro using a thrombin generation assay (TGA) with FVIII-deficient patient plasma, and in vivo by inducing bleeding in FVIII-neutralizing antibody-treated acquired hemophilia A cynomolgus monkey (cyno) model. To clarify the FVIII-cofactor activity of NXT007, we performed an enzymatic kinetics analysis of FIXa-catalyzed FX activation with and without NXT007, as well as surface plasmon resonance analysis to determine the dissociation constant (KD) of NXT007 to FIX, FIXa, FX and FXa. We obtained its pharmacokinetic (PK) profile in non-human primates in a single dose SC/IV study. Results In vitro addition of NXT007 at 30 μg/mL increased the peak height of TGA in FVIII-deficient plasma to the same levels achieved by recombinant human FVIII at 40-100 IU/dL (FXIa-triggering) or 100-150 IU/dL (tissue factor-triggering). A single bolus intravenous injection of NXT007 (0.075 mg/kg) ameliorated bleeding symptoms in the cyno model to similar as a twice daily intravenous injection of recombinant porcine FVIII (20 U/kg). The in vitro and in vivo results were roughly concordant. NXT007 increased the turnover rate (kcat) of FIXa-catalyzed FX activation by approximately 4,000-folds compared to the condition without cofactor. The impact of NXT007 on the kcat was similar to that of emicizumab. As for binding affinities, the KD values of NXT007 to FIX, FIXa, FX and FXa were 1.08, 0.728, 0.0538 and 0.0231 μM, respectively in buffer solution. Compared to emicizumab, NXT007 bound more strongly to FX/FXa and with similar affinity to FIX/FIXa. This means that NXT007 would have an ability to form more FIX-BsAb-FX ternary complex than emicizumab. Calculated using the above KD values, at 30 μg/mL of BsAb the estimated concentration of FIX-NXT007-FX ternary complex in plasma is approximately 10-fold higher than that of the FIX-emicizumab-FX ternary complex which is roughly concordant with the difference in their FVIII equivalent thrombin generation activity. Prothrombin time (PT) was not clearly prolonged suggesting minimal impact on FX function by in vitro addition of NXT007 at up to 30 μg/mL, which was enough to induce sufficient thrombin burst in FVIII-deficient plasma as described above. A half-life of NXT007 was 19.6 to 24.4 days (0.02-2 mg/kg, SC) and SC bioavailability was 84.4% (2 mg/kg) in the in vivo cyno PK study, in which no obvious change in plasma FIX or FX levels was observed after 0.02-2 mg/kg single SC administration. Conclusions Based on the nonclinical results, NXT007, delivered in every-4-week SC injections, will keep a non-hemophilic range of equivalent FVIII thrombin generation in PwHA, Compared with emicizumab, NXT007's improved cofactor activity may be attributed to its more efficient ternary complex formation while keeping turnover rate with minimal impact on FX function suggested by PT value and antigen accumulation. A phase 1/2 clinical study of NXT007 is now on-going (NXTAGE; JapicCTI-194919). Disclosures Yamaguchi: Chugai Pharmaceutical Co., Ltd: Current Employment. Soeda:Chugai Pharmaceutical Co., Ltd.: Current Employment. Sato:Chugai Pharmaceutical Co., Ltd.: Current Employment. Shibahara:Chugai Pharmaceutical Co., Ltd.: Current Employment. Koga:Chugai Pharmaceutical Co., Ltd.: Current Employment. Ichiki:Chugai Pharmaceutical Co., Ltd.: Current Employment. Joyashiki:Chugai Pharmaceutical Co., Ltd.: Current Employment. Teranishi:Chugai Pharmaceutical Co., Ltd.: Current Employment. Nishimura:Chugai Pharmaceutical Co., Ltd.: Current Employment. Shiraiwa:Chugai Pharmaceutical Co., Ltd.: Current Employment. Kitamura:Chugai Pharmaceutical Co., Ltd.: Current Employment. Igawa:Chugai Pharmaceutical Co., Ltd.: Current Employment. Konishi:Chugai Pharmaceutical Co., Ltd.: Current Employment. Kitazawa:Chugai Pharmaceutical Co., Ltd.: Current Employment.
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Imaseki, Hitoshi, und Masae Yukawa. „Introduction of PIXE analysis system in NIRS“. International Journal of PIXE 10, Nr. 03n04 (Januar 2000): 77–90. http://dx.doi.org/10.1142/s0129083500000122.
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In March 1999, electrostatic accelerator, Tandetron (Model 4117MC, High Voltage Engineering Europe Co.) was installed in the Electrostatic Accelerator Building for PIXE (Particle Induced X-ray Emission) analysis. The accelerating voltage is 0.4 to 1.7MV, and the maximum beam current is 5μA at 3.4MeV. This system has three beam ports for different types of PIXE analysis: normal, micro-beam and in-air. The first beam port is used for normal PIXE. Since two types of X-ray detecting device, Si ( Li ) and CdZnTe detectors, are available here, elements from Na ( Z =11) to U ( Z =92) are detectable. Fifteen samples can semi automatically be measured at one time using a proton beam of optical beam size from 0.5 to 2.0 mm at 100 nA beam current. A quadrupole triplet magnet (Model OM2000, Oxford Micro beams, Ltd.) attached to the second beam port produces a proton micro-beam of square shape less than 1μ m ×1μ m . Micro-beam scanning PIXE analysis is carried out with this beam at 50pA current and scanning area up to 2.0mm square. The in-air PIXE analysis is performed using the third beam port. The operation of this machine has been scheduled to start from April 2000 and is controlled by Division of Technology and Safety. Some results preliminarily obtained are also shorn.
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Saidah, Karimatus, und Rian Damariswara. „Pengembangan Bahan Ajar Materi Dongeng Berbasis Kearifan Lokal Jawa Timur Bagi Siswa Kelas III SD“. Premiere Educandum : Jurnal Pendidikan Dasar dan Pembelajaran 9, Nr. 1 (21.06.2019): 73. http://dx.doi.org/10.25273/pe.v9i1.4320.
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<p class="normal" align="center"><span dir="LTR"><strong>Abstrak </strong></span></p><p class="normal"> </p><p class="normal" align="justify"><span dir="LTR">Tujuan dari penelitian ini adalah (1)untuk mengembangkan bahan ajar materi dongeng yang di peruntukkan kelas tiga sekolah dasar dengan mengangkat kearifan lokal Jawa Timur (2) Mengetahui kevalidan bahan ajar materi dongeng yang telah dikembangkan (3) Mengetahui kepraktisan bahan ajar materi dongeng yang telah dikembangkan. Metode penelitian yang digunakan adalah model penelitian pengembangan dengan menggunakan model pengembangan yang dikemukakan oleh borg & Gall.Tahapan borg and gall diantaranya sebagai berikut </span><span lang="id-ID" dir="LTR">a.</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">l</span><span lang="id-ID" dir="LTR">is</span><span lang="id-ID" dir="LTR">i</span><span lang="id-ID" dir="LTR">s</span><span lang="id-ID" dir="LTR">k</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">butuhan d</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">g</span><span lang="id-ID" dir="LTR">umpu</span><span lang="id-ID" dir="LTR">l</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">d</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">ta, b. Tahap perencanaan, c. </span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">ng</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">m</span><span lang="id-ID" dir="LTR">b</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">ng</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n </span><span lang="id-ID" dir="LTR">r</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">ca</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">g</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n produk, d. uji</span><span lang="id-ID" dir="LTR">tah</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">p aw</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">l</span><span lang="id-ID" dir="LTR">(v</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">l</span><span lang="id-ID" dir="LTR">i</span><span lang="id-ID" dir="LTR">d</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">si</span><span lang="id-ID" dir="LTR">)</span><span lang="id-ID" dir="LTR">, e. r</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">visi</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">r</span><span lang="id-ID" dir="LTR">oduk</span><span lang="id-ID" dir="LTR">aw</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">l f. </span><span lang="id-ID" dir="LTR">uji</span><span lang="id-ID" dir="LTR">c</span><span lang="id-ID" dir="LTR">oba</span><span lang="id-ID" dir="LTR">lap</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">ng</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR"> t</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">rb</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">tas, g. </span><span lang="id-ID" dir="LTR">r</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">visi</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">rodu</span><span lang="id-ID" dir="LTR">k, h.</span><span lang="id-ID" dir="LTR"> uji</span><span lang="id-ID" dir="LTR"> l</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">g</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n, i. p</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">y</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">m</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">u</span><span lang="id-ID" dir="LTR">rn</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">p</span><span lang="id-ID" dir="LTR">r</span><span lang="id-ID" dir="LTR">oduk</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">khir, j. diseminasi</span><span lang="id-ID" dir="LTR">d</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">n</span><span lang="id-ID" dir="LTR">i</span><span lang="id-ID" dir="LTR">mp</span><span lang="id-ID" dir="LTR">l</span><span lang="id-ID" dir="LTR">e</span><span lang="id-ID" dir="LTR">ment</span><span lang="id-ID" dir="LTR">a</span><span lang="id-ID" dir="LTR">s</span><span lang="id-ID" dir="LTR">i</span><span lang="id-ID" dir="LTR">.</span><span dir="LTR"> Hasil penelitian ini menunjukkan bahwa bahan ajar yang di kembangkan dinyatakan sangat valid, sangat tuntas dan dapat digunakan dengan skor 85.8% berdasarkan hasil validasi dari ahli pembelajaran Bahasa Indonesia. Untuk mengetahui kepraktisan bahan ajar dilakukan validasi kepada pengguna dan uji coba. Hasl validasi pengguna menunjukkan bahwa bahan ajar yang dikembangkan dapat digunakan dengan skor 91 %. Hasil uji coba produk menunjukkan bahwa siswa dapat menggunakan bahan ajar dengan baik.</span></p>
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Deming, D., T. Hewagama, D. E. Jennings, G. McCabe und G. Wiedemann. „Vector Magnetometry Using the 12-μm Emission Lines“. Symposium - International Astronomical Union 154 (1994): 379–92. http://dx.doi.org/10.1017/s0074180900124659.
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Recent polarimetric observations of the 12.32-μm emission line have provided the observational basis for deriving vector magnetic fields in the upper photosphere with great sensitivity. We use a line source function from the non-LTE model of Carlsson, Rutten and Shchukina, and calculate the radiative transfer of the Stokes I, Q, U, and V profiles. The results show that the profiles are not significantly affected by magneto-optical effects or by saturation, and reliable vector fields can be extracted by simply fitting the Seares relations to the Stokes profiles. Vector field observations for sunspots have shown that the field extends well beyond the photometric boundary of the sunspot, but that the field strength at the penumbral/photospheric boundary is less than half of the sunspot-center value. Within a mature sunspot, the 12-μm line profiles contain essentially no unpolarized radiation, indicating that the field is not intermittent in the sense of containing discrete flux tubes separated by field-free regions. We describe the design of a 12-μm Stokes polarimeter incorporating a high-resolution Fabry-Perot etalon and a 128 × 128 infrared array detector.
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Manouare, Ahmed Zakaria, Saida Ibnyaich, Divitha Seetharamdoo, Abdelaziz EL Idrissi und Abdelilah Ghammaz. „Design, Fabrication and Measurement of a Novel Compact Triband CPW-Fed Planar Monopole Antenna Using Multi-type Slots for Wireless Communication Applications“. Journal of Circuits, Systems and Computers 29, Nr. 02 (24.04.2019): 2050032. http://dx.doi.org/10.1142/s0218126620500322.
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A novel compact coplanar waveguide (CPW)-fed planar monopole antenna with triple-band operation is presented for simultaneously satisfying the LTE 2600, WiMAX, WLAN and X-band applications. It is printed on a single-layered FR4 substrate. In this paper, the proposed antenna, which occupies a small volume of [Formula: see text][Formula: see text]mm3 including the ground plane, is simply composed of a CPW-fed monopole with U-, L- and T-shaped slots. By carefully selecting the lengths and positions of both L-shaped and U-shaped slots, a good dual notched band characteristic at center-rejected frequencies of 3.10[Formula: see text]GHz and 4.50[Formula: see text]GHz can be achieved, respectively. The T-shaped slot is etched on the radiating element to excite a resonant frequency in the 7[Formula: see text]GHz band. Then, to prove the validation of the typical design, a prototype model is fabricated and measured. The experimental result shows that the three frequency bands of 2.31–2.80[Formula: see text]GHz (490[Formula: see text]MHz), 3.37–3.84[Formula: see text]GHz (470[Formula: see text]MHz) and 5.04–7.94[Formula: see text]GHz (2900[Formula: see text]MHz) can successfully cover the desired bandwidths of LTE2600/WiMAX (3.50/5.50[Formula: see text]GHz)/WLAN (5.20/5.80[Formula: see text]GHz) and the X-band communication systems (7.1-GHz operation). The principal applications of the X-band are radar, aircraft, spacecraft and mobile or satellite communication system. Nearly omnidirectional and bidirectional radiation patterns of the triband antenna are observed in both H- and E-planes, respectively. In addition, a reasonable gain over the operating bands has been obtained. Indeed, the good agreements between simulation and measurement results have validated the proposed structure, confirming its potential for multiband wireless communication services.
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Kim, Yong Suk, Ho Jung Song und Ju Hyuck Han. „A Study on the Development of Deepfake-Based Deep Learning Algorithm for the Detection of Medical Data Manipulation“. Webology 19, Nr. 1 (20.01.2022): 4396–409. http://dx.doi.org/10.14704/web/v19i1/web19289.
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In the medical field, the abuse of manipulation data through image processing technology of deep learning is fatal. Therefore, research on detection of modulation on medical images is essential. The data set for fundus data manipulation used 356 right fundus images of 4 lesions (normal, diabetic retinopathy, glaucoma, macular degeneration) out of about 6,000 data collected by Shangong Medical Technology Co., Ltd. The training and verification dataset of the manipulation detection model used original data and U-Net manipulation data. In addition, data manipulated in the Cycle General Adversarial Network (GAN) model were used for the diversity of verification. In this paper, three ophthalmologists and two general doctors were asked to verify the above modulation data. Verification was requested for each lesion, and the verification results were shown through the Receiver operating characteristic (ROC) curve and the Area Under the Curve (AUC). The verification of this study evaluated a total of 100 randomly extracted manipulation data and original data as Observer Performance Test (OPT) for each group. When the evaluation results were digitized as average scores, the scores of ophthalmologists group: 0.72 and general doctors group: 0.67 were recorded. The manipulated images were so similar that both ophthalmologists and general doctors could not find about 30%. However, the manipulation detection model studied in this paper was excellent in about 20% of the group OPT score with a lesion average of 0.913 in the same data group. Therefore, it can be seen that the manipulation detection model of this study finds the manipulated image and the original image well. The future plan is to expand the scope of manipulation detection data to conduct research on various medical data. After that, it will verify its availability at the actual site.
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Wahyu, Widiantara Fauzi, Daryati Daryati und Saleh Rosmawita. „Penerapan Model Pembelajaran Flipped Classroom pada Mata Pelajaran Dasar-Dasar Konstruksi Bangunan dan Teknik Pengukuran Tanah“. Indonesian Journal Of Civil Engineering Education 8, Nr. 2 (27.01.2023): 82. http://dx.doi.org/10.20961/ijcee.v8i2.70885.
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<p dir="ltr"><span>Abstrak:</span><span>Penelitian ini bertujuan untuk mengetahui efektivitas dengan cara penerapan </span><span>flipped classroom</span><span> dalam mata pelajaran Dasar-Dasar Konstruksi dan Properti. Metode penelitian yang digunakan dalam penelitian ini adalah </span><span>quasi experimental </span><span>dengan bentuk </span><span>randomized pretest-posttest control group design. </span><span>Pengumpulan data dilakukan dengan instrument </span><span>pretest dan posttest </span><span>yang diberikan pada dua kelas, eksperimen dan kontrol. Uji statistik yang digunakan adalah statistik </span><span>non-parametrik </span><span>dengan uji </span><span>Mann-Whitney U</span><span>, didapatkan nilai Asymp.Sig (2-tailed)<</span><span>𝖺𝑡𝑎𝑏𝑒𝑙</span><span> (0,05) yang berarti terdapat perbedaan signifikansi data </span><span>posttest </span><span>kelas eksperimen dan kelas kontrol. pembelajaran berbasis multimedia tersebut masuk dalam kategori </span><span>average </span><span>atau cukup efektif. Hasil penelitian menunjukan bahwa terjadi peningkatan pada kelas eksperimen yang diberikan </span><span>treatment </span><span>dengan menerapkan </span><span>flipped classroom </span><span>pada </span><span>platform </span><span>edmodo, dibandingkan dengan kelas kontrol yang tidak diberikan </span><span>treatment</span><span>. Dengan demikian dapat disimpulkan bahwa </span><span>flipped classroom </span><span>pada </span><span>platform </span><span>edmodo efektif dalam meningkatkan hasil belajar yang signifikan pada mata pelajaran Dasar-Dasar Konstruksi dan Teknik Pengukuran Tanah.</span></p><span id="docs-internal-guid-64d6d93e-7fff-a1bc-f239-ee5837d02140"><span>Abstract: </span><span>This study aims to determine the effectiveness of the application of the flipped classroom in the subject of Construction and Property Fundamentals. The research method used in this study is a quasi-experimental with the form of a randomized pretest-posttest control group design.Data was collected using pretest and posttest instruments given to two classes, experimental and control. The statistical test used is non-parametric statistics with the Mann-Whitney U test, the value of Asymp.Sig (2-tailed) <</span><span>𝖺𝑡𝑎𝑏𝑒𝑙</span><span> (0.05) means that there is a significant difference in the posttest data of the experimental class and the control class. The multimedia-based learning is categorized as average or quite effective The results showed that there was an average increase in learning outcomes of 58% in the experimental class that was given treatment by applying the flipped classroom on the Edmodo platform, compared to the control class that was not given treatment. Thus, it can be concluded that the flipped classroom on the Edmodo platform is effective in increasing significant learning outcomes in the subjects of Construction Fundamentals and Soil Measurement Techniques.</span></span>
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Abhay, Simone Shah, Dhanraj Ganapathy, Deepak Nallaswamy Veeraiyan, Padma Ariga, Artak Heboyan, Pokpong Amornvit, Dinesh Rokaya und Viritpon Srimaneepong. „Wear Resistance, Color Stability and Displacement Resistance of Milled PEEK Crowns Compared to Zirconia Crowns under Stimulated Chewing and High-Performance Aging“. Polymers 13, Nr. 21 (30.10.2021): 3761. http://dx.doi.org/10.3390/polym13213761.
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Recently, polyetheretherketone (PEEK) has been introduced to the dental market as a high-performance and chemically inert biomaterial. This study aimed to compare the wear resistance, abrasiveness, color stability, and displacement resistance of zirconia and PEEK milled crowns. An ideal tooth preparation of a first maxillary molar was done and scanned by an intraoral scanner to make a digital model. Then, the prosthetic crown was digitally designed on the CAD software, and the STL file was milled in zirconia (CaroZiir S, Carol Zircolite Pvt. Ltd., Gujarat, India) and PEEK (BioHpp, Bredent GmbH, Senden, Germany) crowns using five-axis CNC milling machines. The wear resistance, color stability, and displacement resistance of the milled monolithic zirconia with unfilled PEEK crowns using a chewing simulator with thermocyclic aging (120,000 cycles) were compared. The antagonist wear, material wear, color stability, and displacement were evaluated and compared among the groups using the Wilcoxon–Mann–Whitney U-test. Zirconia was shown to be three times more abrasive than PEEK (p value < 0.05). Zirconia had twice the wear resistance of PEEK (p value < 0.05). Zirconia was more color stable than PEEK (p value < 0.05). PEEK had more displacement resistance than zirconia (p value < 0.05). PEEK offers minimal abrasion, better stress modulation through plastic deformation, and good color stability, which make it a promising alternative to zirconia crown.
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Chechliński, Łukasz, Barbara Siemiątkowska und Michał Majewski. „A System for Weeds and Crops Identification—Reaching over 10 FPS on Raspberry Pi with the Usage of MobileNets, DenseNet and Custom Modifications“. Sensors 19, Nr. 17 (31.08.2019): 3787. http://dx.doi.org/10.3390/s19173787.
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Automated weeding is an important research area in agrorobotics. Weeds can be removed mechanically or with the precise usage of herbicides. Deep Learning techniques achieved state of the art results in many computer vision tasks, however their deployment on low-cost mobile computers is still challenging. The described system contains several novelties, compared both with its previous version and related work. It is a part of a project of the automatic weeding machine, developed by the Warsaw University of Technology and MCMS Warka Ltd. Obtained models reach satisfying accuracy (detecting 47–67% of weed area, misclasifing as weed 0.1–0.9% of crop area) at over 10 FPS on the Raspberry Pi 3B+ computer. It was tested for four different plant species at different growth stadiums and lighting conditions. The system performing semantic segmentation is based on Convolutional Neural Networks. Its custom architecture combines U-Net, MobileNets, DenseNet and ResNet concepts. Amount of needed manual ground truth labels was significantly decreased by the usage of the knowledge distillation process, learning final model which mimics an ensemble of complex models on a large database of unlabeled data. Further decrease of the inference time was obtained by two custom modifications: in the usage of separable convolutions in DenseNet block and in the number of channels in each layer. In the authors’ opinion, the described novelties can be easily transferred to other agrorobotics tasks.
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Bond, Howard E., und R. Earle Luck. „S-Process Deficiencies in Low-Mass Supergiant Variables“. International Astronomical Union Colloquium 106 (1989): 154. http://dx.doi.org/10.1017/s0252921100062849.
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We have carried out abundance analyses of four low-mass supergiant variable stars (the RV Tauri or RV Tau-like variables AI Cmi, RU Cen, and U Mon, and the Type II Cepheid Kappa Pav) and two Population I Cepheids (CO Aur and V378 Cen). We used model atmospheres in which hydrostatic equilibrium, plane-parallel geometry, and local thermodynamic equilibrium (LTE) were assumed. Discussion of the results, and of published analyses of additional low-mass variables, leads to the following conclusions. (1) The Population I Cepheids show normal, solar elemental abundance ratios (except for the CNO elements, which have been altered by hydrogen burning), lending some support to the validity of the above assumptions for analyses of luminous variable stars. (2) The low-mass variables show metallicities ranging from solar down to [Fe/H] values typical of thick-disk and, in a few cases, of halo stars. (3) Most low-mass variables show a systematic underabundance of the heavy s- and r-process elements. In a few cases this may indicate that the stars were initially of extremely low metal content, and are now hydrogen deficient. However, most of the variables do not appear to belong to the halo population, nor do they show other abundance patterns seen in halo stars. The origin of these underabundances, and their apparent confinement to luminous variables, are difficult to understand in the context of nuclear processing. (4) The heavy-element underabundances correlate with second ionization potential in a manner suggesting that they are non-LTE phenomenan arising from overionization by Lyman-continuum photons. Why a similar effect is not seen in Population I Cepheids is unclear, but may be related to their generally weaker hydrogen emission. (5) Several low-mass variables, including RU Cen and V553 Cen, show carbon enhancements and solar s-process abundances. Relative to the majority of the Type II variables, these stars are s-process enhanced, and we argue that they are related to the Ba II and CH stars.
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Skoulidis, Ferdinandos, Ralph Schiess, Ruedi Aebersold und Ashok R. Venkitaraman. „An integrated cross-species approach for the discovery of serum-based diagnostic biomarkers of PDAC using a genetically engineered murine model (GEMM).“ Journal of Clinical Oncology 30, Nr. 4_suppl (01.02.2012): 218. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.218.
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218 Background: The development of sensitive and specific biomarkers for the early diagnosis of human pancreatic ductal adenocarcinoma (PDAC) represents a major unmet clinical need. GEMMs that faithfully recapitulate the clinical, histological and molecular features of PDAC and capture its genomic complexity (including that triggered by a truncating germline Brca2 mutation) coupled with state of the art proteomic technologies can overcome some of the challenges associated with the analysis of a heterogeneous human disease. We have conducted a large scale screen for differentially expressed glycoproteins in pancreatic tissue and serum from mice with PDAC, pancreatic intra-epithelial neoplasia (PanIN) and matched healthy controls, using the well validated KPCB model of PDAC. Methods: Tryptic digests of protein extracts from snap frozen PDAC, pre-malignant and normal pancreata were subjected to solid-phase extraction of N-glycopeptides and the samples were analysed on a LTQ Orbitrap XL mass spectrometer. LC-MS feature maps were compared employing SuperHirn software and used for the label-free quantification of corresponding proteins. Primary mPDAC cell lines and their supernatants were also analysed. Selected candidate proteins were then quantified in mouse serum by SRM-based targeted proteomics. Results: 146 glycoproteins were identified as overexpressed by >2 fold (p<0.05, Student’s t test) in PDAC compared to normal pancreas and 60 were prioritised for targeted identification in mouse serum. 12 proteins were significantly upregulated (p<0.01, Mann-Whitney U test ) in the serum of tumour-bearing mice with PDAC compared to controls. Conclusions: Using a state of the art GEMM of PDAC, we have successfully applied a two-stage strategy for the tissue-based identification followed by quantification in murine serum of a panel of glycoproteins that are consistently over-expressed during mPDAC development. Validation in serum collections from patients with PDAC, chronic pancreatitis and healthy controls is underway and updated results will be presented at the conference.
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Sewpaul, Paresh, Donna Ashley und Paul Riley. „The Evolution Between 2001 and 2010 In the Uk Costs of Resolving a Mild to Moderate Bleeding Episode with Pd-aPCC Versus rFVIIa In Haemophilia A Patients with inhibitors.“ Blood 116, Nr. 21 (19.11.2010): 1518. http://dx.doi.org/10.1182/blood.v116.21.1518.1518.
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Abstract Abstract 1518 Introduction: Haemophilia A is a rare inherited bleeding disorder characterised by spontaneous or trauma-related bleeding, most commonly into the joints, leading to pain, swelling and limited movement. Some 30–50% of patients with haemophilia A develop inhibitors to their standard treatment, comprised of FVIII concentrates. There are two bypassing agents used for the management of bleeding episodes in patients with haemophilia A with inhibitors in the UK: recombinant factor VII (rFVIIa, NovoSeven®) and plasma-derived activated prothrombin complex concentrate (pd-aPCC, Feiba®). Objective: A systematic review of the cost-effectiveness of pd-aPCC versus rFVIIa was published in 2003. Since the analysis, costs of bypassing agents in the UK have changed significantly (pd-aPCC +30% from ≤0.57/U to ≤0.74/U; rFVIIa -11% from ≤0.51/mcg to ≤0.46/mcg). The present study examines the evolution in costs of resolving a mild to moderate bleeding episode with treatment initiated outside hospital. Methods: A decision analytic model estimated the expected costs and outcomes of resolving a mild-moderate bleeding episode in patients with haemophilia A with inhibitors. The model compared three treatment regimens in patients with a mean weight 70kg. Each regimen comprised first-, second- and third-line treatment: (1) pd-aPCC-pd-aPCC-rFVIIa; (2) pd-aPCC-rFVIIa-rFVIIa; and (3) rFVIIa-rFVIIa-rFVIIa. Efficacy and dosing of pd-aPCC and rFVIIa were estimated from the published literature, with rFVIIa assumed to resolve 92% of mild-moderate bleeds when used as first and second line treatment and pd-aPCC resolving 79% and 88% of mild-moderate bleeds when used first and second line respectively. Patients whose bleeding episodes were not resolved with first-line treatment were admitted to hospital for second- and third-line treatment. Costs included in the economic model were bypassing agent costs and hospitalisation costs. Results: The different treatment regimens result in different total costs for the resolution of a single mild-moderate bleeding episode with up to three lines of treatment: (1) GBP 13,542 (EUR 15,180); (2) GBP 12,985 (EUR 14,556); and (3) GBP 8,569 (EUR 9,605). Since 2001, the costs of regimens 1 and 2 have increased by 26% and 18%, but regimen 3 has decreased by 11% in the UK. Conclusion: Divergence in the price of pd-aPCC and rFVIIa since 2001 has increased the cost-effectiveness of rFVIIa. The results reinforce the fact that effective first-line treatment with rFVIIa results in lower overall treatment costs due to a reduced need for further treatment and associated hospitalisation costs. Adopting rFVIIa as first-line treatment is cost-saving and more effective compared to reserving rFVIIa as a second- or third-line treatment option. Disclosures: Sewpaul: Novo Nordisk : Employment. Ashley:Novo Nordisk : Employment. Riley:Novo Nordisk Ltd: Employment.
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Ndayikengurukiye, Didier, und Max Mignotte. „Salient Object Detection by LTP Texture Characterization on Opposing Color Pairs under SLICO Superpixel Constraint“. Journal of Imaging 8, Nr. 4 (13.04.2022): 110. http://dx.doi.org/10.3390/jimaging8040110.
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The effortless detection of salient objects by humans has been the subject of research in several fields, including computer vision, as it has many applications. However, salient object detection remains a challenge for many computer models dealing with color and textured images. Most of them process color and texture separately and therefore implicitly consider them as independent features which is not the case in reality. Herein, we propose a novel and efficient strategy, through a simple model, almost without internal parameters, which generates a robust saliency map for a natural image. This strategy consists of integrating color information into local textural patterns to characterize a color micro-texture. It is the simple, yet powerful LTP (Local Ternary Patterns) texture descriptor applied to opposing color pairs of a color space that allows us to achieve this end. Each color micro-texture is represented by a vector whose components are from a superpixel obtained by the SLICO (Simple Linear Iterative Clustering with zero parameter) algorithm, which is simple, fast and exhibits state-of-the-art boundary adherence. The degree of dissimilarity between each pair of color micro-textures is computed by the FastMap method, a fast version of MDS (Multi-dimensional Scaling) that considers the color micro-textures’ non-linearity while preserving their distances. These degrees of dissimilarity give us an intermediate saliency map for each RGB (Red–Green–Blue), HSL (Hue–Saturation–Luminance), LUV (L for luminance, U and V represent chromaticity values) and CMY (Cyan–Magenta–Yellow) color space. The final saliency map is their combination to take advantage of the strength of each of them. The MAE (Mean Absolute Error), MSE (Mean Squared Error) and Fβ measures of our saliency maps, on the five most used datasets show that our model outperformed several state-of-the-art models. Being simple and efficient, our model could be combined with classic models using color contrast for a better performance.
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Platzbecker, Uwe, Ulrich Germing, Aristoteles Giagounidis, Katharina Goetze, Philipp Kiewe, Karin Mayer, Oliver Ottman et al. „ACE-536 Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results from a Phase 2 Study“. Blood 124, Nr. 21 (06.12.2014): 411. http://dx.doi.org/10.1182/blood.v124.21.411.411.
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Abstract Introduction. ACE-536, a recombinant fusion protein containing modified activin receptor type IIB and IgG Fc, is being developed for the treatment of anemias due to ineffective erythropoiesis, such as myelodysplastic syndromes (MDS). Patients with MDS often have elevated levels of erythropoietin (EPO) and may be non-responsive or refractory to erythropoiesis-stimulating agents (ESAs). MDS patients have also been shown to have increased serum GDF11 levels (Suragani R et al., Nature Medicine 2014) and increased Smad 2/3 signaling in the bone marrow (Zhou L et al., Blood 2008). ACE-536 binds to ligands in the TGF-ß superfamily, including GDF11, inhibits Smad 2/3 signaling, and promotes late-stage erythroid differentiation via a mechanism distinct from ESAs. RAP-536 (murine version of ACE-536) reduced Smad 2 signaling, increased hemoglobin (Hb) levels and decreased bone marrow erythroid hyperplasia in a mouse model of MDS (Suragani R et al., Nature Medicine 2014). In a healthy volunteer study, ACE-536 was well-tolerated and increased Hb levels (Attie K et al., Am J Hematol 2014). Aims. This is an ongoing, phase 2, multicenter, open-label, dose-finding study to evaluate the effects of ACE-536 on anemia in patients with Low or Int-1 risk MDS who have either high transfusion burden (HTB, defined as ≥4 units RBCs/8 weeks prior to baseline) or low transfusion burden (LTB, defined as <4 units RBCs/8 weeks prior to baseline). Study outcomes include erythroid response (either Hb increase in LTB patients or reduced transfusion burden in HTB patients), safety, tolerability, PK, and PD biomarkers. Methods.Inclusion criteria included Low or Int-1 risk MDS, age ≥ 18 yr, anemia (defined as either being HTB patient or having baseline Hb < 10.0 g/dL in LTB patient), EPO >500 U/L or nonresponsive/refractory to ESAs, no prior azacitidine or decitabine, and no current treatment with ESA, G-CSF, GM-CSF, or lenalidomide. In the dose escalation phase, ACE-536 was administered by subcutaneous (SC) injection once every 3 weeks in 7 sequential cohorts (n=3-6) at dose levels of 0.125, 0.25, 0.5, 0.75, 1.0, 1.33 and 1.75 mg/kg for up to 5 doses with a 3-month follow-up. An expansion cohort (n=30) is planned, and all patients completing this study may enroll in a 12-month extension study. Results. Preliminary data were available for 26 patients (7 LTB/19 HTB) as of 18 Jul 2014. Median age was 71 yr (range: 27-88 yr), 50% were female, 54% had prior EPO therapy and 15% had prior lenalidomide. 69% were WHO subtype RCMD, and the remaining patients were del(5q), RARS, or RAEB-1. Mean (SD) baseline Hgb for the LTB patients (n=7) was 9.1 (0.4) g/dL. Mean (SD) units RBC transfused in the 8 weeks prior to treatment was 0.9 (1.1) units for the LTB patients and 6.3 (2.4) units for the HTB patients. Two of the 7 LTB patients had an increase in mean Hb ≥1.5 g/dL over 8 weeks compared to baseline. Mean maximum Hb increase in the LTB patients was 0.8, 1.0, 2.2, and 2.7 g/dL in the 0.125 (n=1), 0.25 (n=1), 0.75 (n=3), and 1.75 (n=2) mg/kg dose groups, respectively. Six of the 7 LTB patients achieved RBC transfusion independence (RBC-TI) for ≥8 weeks during the study. Six of the 19 HTB patients had a ≥4 unit or ≥50% reduction in RBC units transfused over an 8-week interval during the treatment period compared to the 8 weeks prior to treatment; five of these 6 patients achieved RBC-TI ≥ 8 weeks during the study (range 71-152 days). Increases in neutrophil count following study drug administration were observed in some patients. ACE-536 was generally well tolerated. No related serious adverse events have been reported to date. The most frequent adverse events regardless of causality were: diarrhea (n=4, grade 1/2), bone pain, fatigue, muscle spasms, myalgia, and nasopharyngitis (n=3 each, grade 1/2). Conclusions. Based on preliminary data in Low or Int-1 MDS patients, ACE-536 administered SC every 3 weeks for up to 5 doses increased Hb levels or decreased transfusion requirement, with a favorable safety profile. These data strongly support further evaluation of longer-term treatment with ACE-536 in patients with MDS. Disclosures Platzbecker: Celgene: Honoraria, Research Funding. Germing:Celgene: Honoraria, Research Funding. Goetze:Celgene Corp: Honoraria; Novartis Pharma: Honoraria. Radsak:Celgene: Research Funding. Hankin:Acceleron Pharma: Employment, Equity Ownership. Wilson:Acceleron Pharma: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership. Attie:Acceleron Pharma: Employment, Equity Ownership.
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Konkyana, Lalitha Bhavani, und Sudhakar Alapati. „Kuznets curve with parabola-shaped ultra-wideband antenna with defected ground plane for communications“. International Journal of Pervasive Computing and Communications 17, Nr. 3 (17.06.2021): 349–59. http://dx.doi.org/10.1108/ijpcc-02-2021-0056.
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Purpose This paper aims to state the configuration of the proposed antenna which is competent to many networks such as LTE and X band applications. The experimental study encountered the significance of the proposed antenna. Design/methodology/approach A novel compact Kuznets curve with parabola-shaped quad-band notched antenna is demonstrated in this paper. The presented prototype is ascertained on a composite material composed of woven fiberglass cloth with an epoxy resin binder. The resulting ultra-wideband antenna ranges 3.1–3.54 GHz, 5.17–5.51 GHz, 5.74–6.43 GHz and 6.79–7.60 GHz. To avoid the frequency bands which cause UWB interference,the projected antenna has been incorporated with slotted patch. The proposed antenna design is attained in four steps. The simple circular patch antenna model with defected ground plane is subjected to stepwise progression by including parabola-shaped slot and U shaped slot on the patch to attain four notched bands. Findings This projected antenna possesses an optimal bond among simulated and measured outcomes,which is more suitable for the quad notched band applications. Substrate analysis is done by varying substrate material, and notch behavior is presented. The proposed method’s optimum performance in metrics such as return loss, voltage standing wave ratio and radiation pattern varies its frequency range from 2.56 to 7.6 GHz. Originality/value The antenna adaptation of the defected ground plane has achieved through the quad notched band with operating frequency ranges 2.56 to 7.6 GHz and with eliminated frequency ranges 3.55–5.16 GHz, 5.52–5.73 GHz, 6.44–6.78 GHz and 7.66–10.6 GHz.
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Kasuda, Shogo, Hideto Matsui, Shiro Ono, Yasunori Matsunari, Kenji Nishio, Midori Shima, Katsuhiko Hatake und Mitsuhiko Sugimoto. „Von Willebrand Factor-Dependent Inflammatory Responses in Mouse Septic Model By Cecal Ligation and Puncture“. Blood 124, Nr. 21 (06.12.2014): 2773. http://dx.doi.org/10.1182/blood.v124.21.2773.2773.
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Abstract Sepsis is a serious inflammatory response syndrome, in which systemic activation of both inflammatory and coagulation pathways are provoked by severe microbial infection. In addition to the known hemostatic functions, von Willebrand factor (VWF) is recently assumed to participate in a cross-talk between inflammation and thrombosis. Indeed, recent mouse model studies demonstrated that proper functional regulation of VWF-dependent inflammatory responses by ADAMTS13 considerably improved the disease progression of brain stroke or myocardial infarction. However, little is known about the detailed mechanisms or relevant role of VWF functions in inflammation. We therefore studied the physiologic relevance of VWF-dependent inflammatory responses in a mouse model of experimental sepsis by cecal ligation and puncture (CLP). The mouse CLP was performed according to the established standard protocol (Rittirsch D, et al., Nat Protoc, 2009). Briefly, mouse cecum was ligated distal to the ileocecal valve under laparotomy, punctured with 18 gauge needle and gently pressed until a small drop of stool appeared. The cecum was returned to the peritoneal cavity and 200 μL of saline was injected into the cavity to avoid dehydration before body wall and skin incision were closed with a 4-0 Sofsilk. We compared 17 wild-type (WT) and 17 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME), all of which were 10-12 weeks of age, healthy and fertile. Excess blood loss was not observed in all (WT or KO) mice during the CLP operation. Kaplan-Meier analysis revealed the significantly (p < 0.05) lower survival rate of KO mice than that of WT (KO; 23.5% vs. WT; 58.8% at the Day 7 of CLP). The impaired survival rate of KO mice was restored by the bolus administration of human VWF (n=21, 2.5 U/mouse) to an extent comparable to that of WT. Peripheral blood analysis of KO mice at 24 hours after CLP showed the severe leukocytopenia with sharp decrease of neutrophils in blood, as compared to WT. In addition, formation of walled-off abscess was confirmed at the peri-cecal space in all the WT and KO mice alive even at the Day 7 of CLP, while such focal abscess formation was not found in mice died before the Day 3 of CLP. Thus, our results altogether indicate that VWF could play a role on the recruitment or accumulation of neutrophils for microbial killing at the local inflammatory focus. VWF-mediated platelet aggregate formation in peripheral capillary vessels then could shut down the local microcirculation, thereby blocking systemic microbial expansion as a crucial biological defense mechanism. Disclosures Shima: Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Kater, Arnon P., Tong Lu, Anton W. Langerak, Clemens Mellink, Brenda Chyla, Jenny Qun Wu, Michelle Boyer, Marcus Lefebure, Yanwen Jiang und John F. Seymour. „Chronic Lymphocytic Leukemia (CLL) Clonal Growth Rate Is Slower Following Venetoclax-Rituximab (VenR): Results from a Minimal Residual Disease (MRD) Model from the Randomized Phase 3 Murano Trial“. Blood 138, Supplement 1 (05.11.2021): 1551. http://dx.doi.org/10.1182/blood-2021-148612.
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Abstract Introduction: At a median follow-up of 5 years (cutoff of May 8, 2020), the MURANO trial (NCT02005471) demonstrated deeper responses, including superior rates of undetectable (u)MRD and progression-free survival, in patients (pts) with relapsed/refractory (R/R) CLL treated with fixed-duration VenR vs bendamustine-rituximab (BR). With longitudinal MRD assessments in peripheral blood (PB), we now report kinetics of MRD growth after end of treatment (EOT), and the clinical and molecular factors associated with MRD growth rates. Methods: Pts were randomized to VenR (venetoclax 400mg daily for 2 years + standard-dose rituximab for the first 6 months) or BR (6 months). PB MRD samples were collected every 3-6 months and analyzed centrally by allele-specific oligonucleotide-polymerase chain reaction and/or flow cytometry; uMRD threshold was <10 −4. Mutations were identified using whole-exome sequencing on available DNA specimens from CD19-enriched baseline samples. For longitudinal analysis of MRD growth dynamics, a population-based logistic growth model with a nonlinear mixed effects approach was developed as previously described (Al-Sawaf et al. EHA 2021). Pts who completed treatment (Tx) without progressive disease (PD) and who had ≥2 measurable time points post-EOT were included; data below the lower limit of quantification in those pts was handled by a likelihood-based method (Bergstrand & Karlsson, AAPS J 2009). Prognostic markers and patient demographics were screened as covariates for impact on key model parameters, based on statistical and graphical assessments. Variables with >20% missing data or with low representation (<10% in any category) were excluded from the analysis. Statistical inference on MRD doubling time was derived for the stratified subgroups; all p-values are descriptive. Results: Overall, 284 pts completed the study Tx without PD. Pts with no MRD data (n=23), pts with MRD data only on-Tx (n=6) or only after PD/next-line of Tx (n=2), or pts with <2 measurable MRD values (n=42) were excluded, leaving a total of 211 pts (91 VenR-treated and 120 BR-treated) included in the analysis. With a faster time to PD for the BR arm, median duration of MRD data collection post-EOT was 395 days for BR-treated pts and 735 days for VenR-treated pts. The median MRD level at EOT was significantly lower after VenR (1.88 x 10 −5) than BR (7.06 x 10 −4; p=5.1 x 10 −8, Figure 1A). In the VenR arm, no statistically significant difference in median MRD level at EOT was seen in pts with mutated or unmutated immunoglobulin heavy chain variable gene (IGHV), or pts with or without TP53 mutation (Table 1). However, in the BR arm, pts with TP53 mutation had significantly higher median MRD levels at EOT than those with TP53 wild-type (Table 1). Overall, median MRD doubling time post-EOT was significantly longer for pts treated with VenR (93 days; n=91) than BR (53 days; n=120; p=1.2 x 10 −7, Figure 1B). Based on covariate screening of 27 prognostic markers and patient demographics, age (< or ≥65 years), VenR Tx, IGHV status, TP53 mutation status, and disease burden at study initiation (low/medium risk of tumor lysis syndrome vs high risk) showed significant impact on MRD growth rate (Table 1). The median MRD doubling time was 53 days in pts aged <65 years (n=92) and 66 days in pts aged ≥65 years (n=119; p=0.013); similar differences were seen in both Tx arms (Table 1). After adjusting the other three covariates in the model, the effect of VenR Tx on MRD growth rate remained statistically significant (0.51-fold of that for the BR arm, 95% confidence interval, 0.41-0.64). Conclusion: Using a robust, population-based model of MRD growth dynamics, we demonstrate that post-EOT MRD growth was slower in pts with R/R CLL treated with VenR compared with BR. Together with similar observations in the frontline setting of venetoclax-obinutuzumab Tx, these results suggest that, compared with chemoimmunotherapy, fixed-duration venetoclax plus anti-CD20 therapy may contribute to prolonged CLL disease control by slowing the growth of the residual disease clones. It also implies that clonal growth may be influenced by biological and Tx-related parameters. The underlying mechanisms need to be further explored. Figure 1 Figure 1. Disclosures Kater: Abbvie: Honoraria, Other: Ad Board, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee. Lu: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company. Langerak: Erasmus MS, University Medical Center: Current Employment; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Research Funding; Gilead: Research Funding; Janssen: Speakers Bureau. Mellink: Cytogenetic Field: Consultancy; Genome Diagnostics Laboratory, AUMC: Current Employment; Financial support related to microarray analysis of Murano samples: Research Funding. Chyla: AbbVie: Current Employment, Current equity holder in publicly-traded company. Wu: Genentech, Inc.: Current Employment; Roche/GNE: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Boyer: Roche: Current Employment. Lefebure: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Roche: Current Employment. Jiang: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc./F.Hoffmann-La Roche Ltd: Current Employment. Seymour: Sunesis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Mei Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Peng, Wenqing, und Shenghua Feng. „Research on the Support Technology for Deep Large-Section Refuge Chambers in Broken Surrounding Rock in a Roadway“. Applied Sciences 14, Nr. 17 (26.08.2024): 7527. http://dx.doi.org/10.3390/app14177527.
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The phenomenon of peripheral rock instability is more common in crushed bedrock roadways, and the fundamental reason for this lies in the significantly different characteristics of its peripheral rock stress field. Taking the newly dug belt inclined shaft of PingDingShan TianAn Coal Co., Ltd. No. 6 Mine as the engineering background, a mechanical model of a broken perimeter rock roadway was established by using classical rock mechanics theory. Stress distribution around the roadway of the broken perimeter rock medium was systematically analyzed, and radial and tangential stress formulas of the broken perimeter rock were deduced. Through the formula calculation, it was deduced that there was a stress drop in the intact surrounding rock outside the disturbed zone, and the radial stress of the intact surrounding rock in its deep part was relatively increased, while the tangential stress was relatively decreased. The existence of crushed surrounding rock increased the minimum principal stress and decreased the maximum principal stress of the unfractured surrounding rock, which proves that a well-maintained disturbed zone can play a lining role. Thus, a “U-shaped steel + inverted arch + bottom arch linkage beam + floor bolt compensation” support program was proposed. This joint support program easily forms a closed support structure, which is more effective in controlling the deformation of tunnel perimeter rock. The support structure can effectively resist the deformation of the surrounding rock and enhance bottom drum resistance. Through numerical simulation, it was concluded that the horizontal displacement of the two gangs was reduced by 70%, and the displacement of the top and bottom plates was reduced by 77% after optimization of the support, which effectively controlled the stability of the broken surrounding rock.