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RocíoOviedoZampaña, M., Jesús Flores González, Antonio J. Guerrero Altamirano, Jesus Martínez Faure und Juan A. Péculo Carrasco. „AP036 Comparision between in-and out-of-hospital cardiac arrest: 320 CPR analyzed“. Resuscitation 82 (Oktober 2011): S18. http://dx.doi.org/10.1016/s0300-9572(11)70070-3.
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Francis, Lanie, Judy Anderson, Michael Timm, Noriyoshi Kurihara, Ujjal Singha, Yazan Alsayed, Alissa Huston, Suzanne Lentzsch, G. David Roodman und Irene M. Ghobrial. „The Effect of Rapamycin, 17-AAG and the Combination on the Bone Marrow Microenvironment in Multiple Myeloma (MM).“ Blood 106, Nr. 11 (16.11.2005): 3476. http://dx.doi.org/10.1182/blood.v106.11.3476.3476.
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Abstract The bone marrow microenvironment in MM is characterized by the presence of upregulated osteoclast activity (OCL) and increased angiogenesis. We have recently demonstrated that the HSP90 inhibitor 17-AAG (provided by the NCI) and the mTOR inhibitor rapamycin (LC Laboratories, MA) have synergistic inhibitory activity on MM cells. The objective of this study was to determine the effect of rapamycin, 17-AAG and the combination on OCL formation and angiogenesis. Rapamycin (0.01–100nM), 17-AAG (10–1000nM) and the combination was tested using an in vitro human OCL formation assay and a human angiogenesis assay (AngioKit, TCS Cellworks, UK). Nonadherent human marrow mononuclear cells (1 x 105/100 μL) were plated in 96-well plates in the presence or absence of DMSO, rapamycin, 17-AAG or the combination. RANKL (100ng/ml) and MCSF (20ng/ml) were added to all wells except control media and MCSF. After 3 weeks, cells were fixed, and the number of OCL-like multinucleated cells were scored. To test the effect of the agents on early OCL precursors, we added the inhibitory agents on days 1, 7 or 14 of the culture. The AngioKit is comprised of human endothelial cells in a 24 well plate. The endothelial cells proliferate and then migrate through the matrix to form tubular structures and anastomosing tubules by 2 weeks. Two control wells were treated with VEGF (+ve control) and two with suramin (−ve control). The optimized medium and test samples were replaced on days 4, 7, and 9 after initial treatment. On day 11, cultures were fixed and stained with antibodies to CD31 to detect vessel formation. The degree of tubule formation was quantitated using computerized image analysis (Angiosys, TCS Cellworks, UK). Single agent rapamycin (20–100nM) inhibited OCL formation by 35% as compared to control in all tested doses indicating that PI3K/mTOR is an important regulator of OCL formation. The effect was similar on day 7 and day 14 indicating that this pathway is important for early and late OCL formation. 17-AAG 100–600nM significantly inhibited OCL formation with 100nM 17-AAG inducing 12% OCL formation as compared to control, while 300 and 600nM completely abrogated OCLs (0% OCLs). This effect was similar at day 7. However, when 17-AAG was added on day 14, it only induced 50–60% reduction in OCL formation indicating that 17-AAG affects early OCL formation. The combination of the two agents completely inhibited OCL formation on day 1 and 7 and led to a 65% reduction in OCLs when added on day 14 of the culture. Rapamycin showed a marked decrease in angiogenesis (similar to the negative control suramin), even at the lowest level tested of 0.01nM. 17-AAG demonstrated some inhibition of angiogenesis at 10 nM, and completely abrogated angiogenesis at 500–1000nM. In summary, rapamycin and 17-AAG inhibit OCL formation and angiogenesis. The effect of 17-AAG was on early OCL formation while rapamycin was on both early and late OCL. These results are contradictory to previous data indicating that 17-AAG increases OCL activity in MM. Rapamycin had a significant inhibitory effect on angiogenesis even at low doses. These results demonstrate that the use of rapamycin analogues and 17-AAG in clinical trials may have a therapeutic effect, not only on MM cells, but also on the bone marrow microenvironment. Supported in part by an ASH Scholar Award and an MMRF grant.
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Lalani, Nafisha, Sue Richter, Peter W. M. Chung, Neil Eric Fleshner, Michael A. Jewett, Alexandre Zlotta, Robert Glen Bristow, Michael Milosevic und Srikala S. Sridhar. „Concurrent cisplatin and radiotherapy: Decision making, tolerability, and outcomes for patients treated in a multidisciplinary bladder clinic.“ Journal of Clinical Oncology 32, Nr. 4_suppl (01.02.2014): 320. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.320.
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320 Background: For select muscle invasive bladder cancer (MIBC) patients, a multimodal approach using transurethral resection of the bladder tumor (TURBT) followed by concurrent cisplatin and external beam radiotherapy (EBRT) provides a curative bladder-sparing alternative to cystectomy. Our aim was to review decision making, tolerability and outcomes for patients treated in a multidisciplinary bladder clinic. Methods: Between June 1998-June 2011, MIBC patients treated with TURBT and concurrent cisplatin (40mg/m2 weekly) with EBRT (60-66Gy in 30-33 fractions to the bladder and pelvis) were identified. Post-treatment cystoscopy was performed every 3 months with regular imaging. Results: A total of 64 patients were assessed; mean age 73 (43-89), 83% were male. The decision to attempt bladder-sparing was based on patient preference (58%), nonsurgical candidate (25%), or unknown (17%). Patients received a mean 5/6 weeks of cisplatin with the most common toxicity being a 14% overall risk of grade 0-1 renal toxicity by NCIC CTC criteria. All patients completed the prescribed EBRT. No patients experienced acute toxicity requiring cystectomy or causing death. At a median follow-up of 3.5 years, 50/64 (78%) patients were alive and had their own bladders, 7/64 (11%) were alive after cystectomy for recurrence, 7/64 (11%) died. Of the 24/64 (38%) recurrences: 3/64 (5%) had positive cytology/carcinoma in-situ and received intravesicle therapy; 1/64 (2%) had local superficial recurrence and underwent TURBT; 7/64 (11%) had local invasive recurrence requiring cystectomy; 13/64 (20%) had distant recurrence, 6 received chemotherapy and 7 were observed. Estimated disease free survival was 51%, and overall survival was 90% at 3.5 years. Conclusions: Bladder-sparing therapy with concurrent cisplatin and EBRT is a well-tolerated and effective approach with outcomes comparable to cystectomy in carefully selected patients. Prospective trials are required to delineate clinical and molecular factors to further triage patients into sub-groups who may benefit from bladder sparing with neoadjuvant/adjuvant chemotherapy or molecularly-targeted agents to improve survival.
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Kuhn, J. G., H. A. Burris, S. F. Jones, D. W. Hein, N. T. Willcutt, F. A. Greco, D. S. Thompson, A. A. Meluch, R. S. Schwartz und D. M. Brown. „Phase I/II dose-escalation trial of amonafide for treatment of advanced solid tumors: Genotyping to optimize dose based on polymorphic metabolism“. Journal of Clinical Oncology 25, Nr. 18_suppl (20.06.2007): 2503. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2503.
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2503 Background: Amonafide (AMF), a synthetic imide derivative of naphthalic acid, is a topoisomerase II inhibitor and is subject to polymorphic metabolism based on acetylation genotype. AMF is extensively metabolized by N-acetyltransferase 2 (NAT2) to N- acetylamonafide (AAMF) which has activity nearly equipotent to AMF. In our phase I evaluation, we observed a correlation between NAT2 genotype, AMF/AAMF pharmacokinetics and toxicity (J Clin Oncol 22 [14S]: 2023, 2004). Patients (pts) with slow (S) acetylator genotype tolerated higher doses than those with rapid/intermediate (R/I) acetylator genotype. The present Phase II portion was designed to prospectively determine the dose of AMF based on NAT2 genotype and focused on selected tumor types. Methods: NAT2 genotyping of genomic DNA from blood samples was done prospectively to determine acetylator status of each pt. AMF was administered IV weekly x 3 q4wk, escalation range 320 to 400 mg/m2 for R/I and 400 to 500 mg/m2 for S acetylators. Primary endpoints: safety, MTD, tumor measurements or sustained decreases in tumor markers. Results: Total 47 pts (21 M/26 F), median 66 yr, PS 0–2, acetylator status R/I (26), S (21) with ovarian (11) or prostate (9), breast (8), colon (4) cancers (CA) and other common tumors refractory to therapy were treated; 30 of 47 pts were dosed based on prospective genotyping. Of these 30 pts, 17 were R/I acetylators: no toxicity at 320 mg/m2 AMF in 7/11 pts and manageable myelosuppresion in 4/11 pts observed days 15–21 of cycle but not dose-limiting (DLT); DLT in 3/6 pts at 400 mg/m2. In the 13 S acetylators: at 400 mg/m2 no DLT in 8 pts; DLT in 2/5 pts treated at 500 mg/m2. Other side effects included nausea/vomiting, fatigue and anemia. Of all 47 pts, biologic activity was seen in 6 pts: 3/9 prostate CA (decreased PSA), 2/11 ovarian CA (decreased CA125) and 1/1 GIST (decreased lymph nodes). Conclusions: MTD determined to be 320 mg/m2 in R/I and 400mg/m2 weekly x 3q 4 weeks in S acetylators, respectively, supporting hypothesis that AMF dosing based on prospective NAT2 genotyping may allow for dose optimization based on drug metabolism and result in better tolerance. Phase II assessments at the MTD dose levels are currently ongoing for prostate cancer. No significant financial relationships to disclose.
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Wei-Tian, Wang, Yang Guang, Chen Zheng-Hao, Zhou Yue-Liang, Lü Hui-Bin und Yang Guo-Zhen. „Large third-order optical nonlinearity in Au nanometre particle doped BaTiO 3 composite films near the resonant frequency“. Chinese Physics 11, Nr. 12 (Dezember 2002): 1324–27. http://dx.doi.org/10.1088/1009-1963/11/12/320.
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Gómez-Amo, J. L., V. Estellés, A. di Sarra, R. Pedrós, M. P. Utrillas, J. A. Martínez- Lozano, C. González-Frias, E. Kyrö und J. M. Vilaplana. „Operational considerations to improve total ozone measurements with a Microtops II ozone monitor“. Atmospheric Measurement Techniques Discussions 4, Nr. 6 (16.12.2011): 7529–58. http://dx.doi.org/10.5194/amtd-4-7529-2011.
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Abstract. A Microtops II "ozone monitor" with UV channels centered at 305.5, 312.5, and 320 nm has been used routinely in six experimental campaigns carried out in several geographic locations and seasons, covering latitudes from 35 to 68° N during the last ten years (2001–2011). The total ozone content is retrieved by Microtops II by using different combinations (Channel I, 305.5/312.5 nm; Channel II, 312.5/320 nm; and Channel III, 305.5/312.5/320 nm) of the signals at the three ultraviolet wavelengths. When a calibration was used and the airmass limit was fixed to 3, Microtops II produce mean relative deviations with respect to the Brewer of 0.1, −11, and 8% respectively for the Channel I, Channel II, and Channel III retrieval. The performance of the Microtops retrieval has been stable during the last ten years. Channel I represents the best option to determine the instantaneous total ozone content. Channel II and III values appear weakly sensitive to temperature, ozone content, and aerosols. Channel II is more stable than Channel I for airmasses larger than 2.6. The conclusions do not show any dependence on latitude and season.
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Zeller, Thomas, Ulrich Frank, Christian Müller, Karlheinz Bürgelin, Uwe Schwarzwälder, Lutz Sinn, Barbara Horn, Helmut Roskamm und Franz-Josef Neumann. „Technological Advances in the Design of Catheters and Devices Used in Renal Artery Interventions: Impact on Complications“. Journal of Endovascular Therapy 10, Nr. 5 (Oktober 2003): 1006–14. http://dx.doi.org/10.1177/152660280301000526.
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Purpose: To analyze the impact of technical improvements in stent devices and guiding catheters (e.g., reduced device diameter, increased flexibility) on the complication rates associated with percutaneous renal artery interventions. Methods: During a 5-year period (1997–2001), 268 consecutive patients (178 men; mean age 67±9 years) had 370 atherosclerotic renal artery stenoses (RAS) ≥70% treated with angioplasty/stenting in 320 procedures. The guiding catheter technique was used routinely until 2000; in 2001, a guiding sheath was used in 29% of cases. From 1997 to 2000, sealing devices were frequently used for sheath removal; during the last year, the sheaths were removed using the Femostop device. Results: In 320 interventions, 32 (10%) complications occurred, with a decreasing frequency during the last 2 years (1996/97: 13% [7/53]; 1998: 16% [9/57]; 1999: 15% [11/74]; 2000: 4% [3/70]; 2001: 3% [2/66]). There were 21 (6.6%) local complications, including 4 cases requiring permanent hemodialysis after the intervention and 11 (3.4%) access site complications. No procedure-related death occurred. During the study period, the average sheath diameter was reduced from 8.15±0.76 F to 6.15±0.63 F (p<0.05). Mean procedural time was reduced from 42±13 minutes to 23±11 minutes (p<0.05). The initial heparin dose was reduced from 10,000 to 5000 units. Conclusions: In parallel with the use of more flexible catheters and premounted stents of lower profile, the complication rate of renal angioplasty/stenting of atherosclerotic RAS has been reduced significantly during a 5-year period.
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Yi, Lu, Li Qing-An, Di Nai-Li, Li Run-Wei, Ma Xiao, Kou Zhi-Qi und Cheng Zhao-Hua. „Evidence of phase separation in Nd 1- x Sr x MnO 3 ( x =0.50, 0.51, 0.52, 0.53, 0.54, 0.55)“. Chinese Physics 12, Nr. 11 (30.10.2003): 1301–4. http://dx.doi.org/10.1088/1009-1963/12/11/320.
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Udupa, Ganesha, M. Singaperumal, R. S. Sirohi und M. P. Kothiyal. „Characterization of surface topography by confocal microscopy: I. Principles and the measurement system“. Measurement Science and Technology 11, Nr. 3 (14.02.2000): 305–14. http://dx.doi.org/10.1088/0957-0233/11/3/320.
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Adjel-Lalouani, Farah, Sara Hammouchi, Nora Trad und Souad Mehalaine. „Interactive effects of salt stress and gibberellic acid (GA3) on germination and ion content of barley (Hordeum vulgare L.)“. South Asian Journal of Experimental Biology 11, Nr. 3 (24.05.2021): 311–20. http://dx.doi.org/10.38150/sajeb.11(3).p311-320.
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Salinity is becoming one of the most important environmental factors lim-iting crop productivity around the world. Different strategies are employed to achieve optimal growth in saline conditions by employing some biochemi-cal agents such as plant hormones. This article provides an experimental investigation that was conducted to explore the effect of salt stress and hor-mones on barley. Three levels of salt stress tests, (0, 100 and 200 mM NaCl) on four barley genotypes (Hordeum vulgare L.): Jaidor, Fouara, Saida, and Tichedrett, were studied. Each test was treated with and without 20 μg/l of Gibberellic acid (GA3). Plants were assessed at germination and seedling growth stages to determine the percentage and the speed of germination, the coleoptile length, and the root length. In addition, the experimental in-vestigation was conducted to explore amount and the ash content of potas-sium and sodium due to salinity and the effect of gibberellic acid application to mitigate the impact of salt stress. The results revealed that the use of gib-berellic acid was beneficial in reducing the depressive effect of salt. In gen-eral, Jaidor registered the best results and Fouara registered the lowest ones. However, Saida and Tichedrett were marked with a high root K/Na ratio. In conclusion, the application of salt stress negatively affected the growth of the four studied genotypes. This effect is even more important as the intensity of the stress is high. However, the application of the GA3 hor-mone reduced the negative impact of the salt stress on all measured param-eters.
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Lyutko, Eugene. „Emergence of the Clerical Corporation in Western Europe (11–13th Centuries) and in Russia (17–18th Centuries)“. Sotsiologicheskoe Obozrenie / Russian Sociological Review 19, Nr. 3 (2020): 300–320. http://dx.doi.org/10.17323/1728-192x-2020-3-300-320.
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Traditional Christian confessions — for example, in Catholicism or in Orthodoxy — in scholarly literature, in modern legislation, or at the level of everyday consciousness, are understood primarily as clerical corporations. This corporate reading of modern Christianity also influences the understanding of the phenomenon of religion itself, as it happens, for example, in the famous essay on the “field of religion” by P. Bourdieu. This reading also determines the perception of Christianity as a historical phenomenon as well, which, within the framework of such a representation, appears as a corporation at every moment of its historical existence. This article argues that a “clerical corporation” is not a form of social organization that was originally inherent in Christianity, but a historical phenomenon that embraces various confessional contexts at different times. In particular, the emergence of a clerical corporation is fixed within the framework of an asynchronous comparative perspective relying on the examples of Western European Catholicism of the 11th — 13th centuries, and Russian Orthodoxy of the 17th — 18th centuries.
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Sardi, Sílvia Inês, Gúbio Soares Campos, Sílvia Bonfim Barros, Gabriela Lorens Edelweiss und Delane Tigre Martins. „Detecção de anticorpos contra o vírus da parainfluenza bovina tipo 3 (pi-3) e o vírus da leucose bovina (vlb) em bovinos de diferentes municípios do Estado da Bahia, Brasil.“ Revista de Ciências Médicas e Biológicas 1, Nr. 1 (30.06.2002): 61. http://dx.doi.org/10.9771/cmbio.v1i1.4108.
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<span class="texto">Neste trabalho, foi avaliada a pesquisa de anticorpos contra o vírus da parainfluenza bovina tipo 3 (PI-3) e o vírus da leucose bovina (VLB), em seis municípios do Estado da Bahia, através de uma amostragem sorológica de 187 bovinos de 1 a 4 anos, sem antecedentes clínicos, vacinação ou diagnóstico laboratorial das doenças em estudo. Do total dos 187 soros analisados para a detecção de anticorpos contra o vírus de PI-3, utilizando a técnica de inibição da hemoaglutinação, 59 soros foram negativos (31,5%) e 128 soros foram positivos (68,5%). Dos 128 soros positivos, 42 soros mostraram ter 80 UIHA, 67 soros, 160-320 UIHA e 11 soros um valor maior do que ou igual a 640 UIHA. Os resultados para VLB, detectados pela técnica de ELISA de uso comercial, mostraram que, dos 187 soros, somente 14 foram positivos (7,5%). Os resultados obtidos são discutidos no trabalho.</span>
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CHAINE, ALINE, CAROLINE LEVY, BERNARD LACOUR, CHRISTOPHE RIEDEL und FRÉDÉRIC CARLIN. „Decontamination of Sugar Syrup by Pulsed Light“. Journal of Food Protection 75, Nr. 5 (01.05.2012): 913–17. http://dx.doi.org/10.4315/0362-028x.jfp-11-342.
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The pulsed light produced by xenon flash lamps was applied to 65 to 67 °Brix sugar syrups artificially contaminated with suspensions of Saccharomyces cerevisiae and with spores of Bacillus subtilis, Geobacillus stearothermophilus, Alicyclobacillus acidoterrestris, and Aspergillus niger. The emitted pulsed light contained 18.5% UV radiation. At least 3-log reductions of S. cerevisiae, B. subtilis, G. stearothermophilus, and A. acidoterrestris suspended in 3-mm-deep volumes of sugar syrup were obtained with a fluence of the incident pulsed light equal to or less than 1.8 J/cm2, and the same results were obtained for B. subtilis and A. acidoterrestris suspended in 10-mm-deep volumes of sugar syrup. A. niger spores would require a more intense treatment; for instance, the maximal log reduction was close to 1 with a fluence of the incident pulsed light of 1.2 J/cm2. A flowthrough reactor with a flow rate of 320 ml/min and a flow gap of 2.15 mm was designed for pulsed light treatment of sugar syrup. Using this device, a 3-log reduction of A. acidoterrestris spores was obtained with 3 to 4 pulses of incident pulsed light at 0.91 J/cm2 per sugar syrup volume.
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Pishvaian, Michael J., Michael Morse, Jennifer T. McDevitt, Song Ren, Gabriel Robbie, Patricia C. Ryan, Serguei Soukharev, Haifeng Bao und Crystal Shereen Denlinger. „Phase 1 dose escalation study of MEDI-565, a bispecific T-cell engager that targets human carcinoembryonic antigen (CEA), in patients with advanced gastrointestinal (GI) adenocarcinomas.“ Journal of Clinical Oncology 34, Nr. 4_suppl (01.02.2016): 320. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.320.
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320 Background: MEDI-565, a bispecific single-chain antibody, targets human CEA on tumor cells and the CD3 epsilon subunit of the human T-cell receptor complex. In murine models, MEDI-565 showed antitumor activity in CEA-expressing tumors (J Immunother 2009;34:341-52). Methods: This phase 1, multicenter, open-label, dose-escalation study enrolled adults with GI adenocarcinomas (including esophageal, gastric, small intestine, colorectal, biliary tract, and pancreatic). MEDI-565 was given intravenously over 3 h on days 1–5 in 28-day cycles, with 4 single-patient (pt) (0.75–20 μg) and 5 standard 3+3 escalation (60 μg–3 mg; 1.5–7.5 mg with dexamethasone [dex]) cohorts. Primary objective was to determine the maximum tolerated dose (MTD); secondary objectives were to evaluate pharmacokinetics (PK), antidrug antibody (ADA), and antitumor activity. Results: Study enrolled39 pts: mean age 59 y; 56% male; 28 (72%) colorectal, 6 (15%) pancreatic, 5 (13%) other. Dose-limiting toxicities (grade ≥ 3 nonhematologic) were seen in 4 pts (2 at 3-mg; 2 at 7.5-mg + dex): hypoxia (n = 2), diarrhea, and cytokine release syndrome (CRS). Grade 3 treatment-related adverse events (AEs) seen in 5 pts: diarrhea, CRS, increased alanine aminotransferase, hypertension (all n = 1), and hypoxia (n = 2). Treatment-related serious AEs seen in 6 pts: diarrhea, vomiting, pyrexia, CRS (all n = 1), and hypoxia (n = 2). Five pts discontinued treatment due to AEs: diarrhea, CRS, central nervous system metastases, and hypoxia (n = 2). MEDI-565 exposures increased in approximately dose-proportional manner, with clearance (35–77 L/d) and half-life (2–7 h) typical of drug class. ADA had minor impact; 19 pts (48.7%) had ADAs, 5/39 (12.8%) with high titer, with decreased MEDI-565 concentrations in 2 pts. Plasma inflammatory cytokines were elevated posttreatment in several pts at 1.5- and 3-mg (no dex) dose levels. No objective responses were observed; 11 (28%) pts had stable disease as best response. Conclusions: The MTD of MEDI-565 in pts with GI adenocarcinomas was 5 mg with dex. PK was linear, with fast clearance and short half-life. No objective responses were observed. Clinical trial information: NCT01284231.
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Wang, Di, Shuang Ying Wei und Li Jiang Hu. „POSS/TiO2 Nanohybrids as Sun Protection Ingredients for Greenhouse Covers“. Advanced Materials Research 113-116 (Juni 2010): 2077–80. http://dx.doi.org/10.4028/www.scientific.net/amr.113-116.2077.
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Based on (3-methacryloxypropyl)-Polyhedral oligomeric silsesquioxane (MP-POSS) (MP), vinyl-POSS (VP), (3-glycidoxypropyl)-POSS (GP) and modified with 10, 20 and 30 wt-% titanium tetrabutoxide (TTB), three hybrid nanofilms (f-MPT, f-VPT and f-GPT) were prepared using hydrolytic condensation and crosslinking. The average transparency (AT) and absorption coefficients (AC) of the films were measured in the ranges of 280-2500 nm. The average transparency (AT) values of three films were about 10-11% (280-320 nm), 78-80% (320-400 nm) and 85-89% (750-2500 nm), which implies that these films indeed can provide a physical barrier for blocking the UV-B absorbed into greenhouse, indicating functionality of the POSS/TiO2 materials as the sun protection ingredients. The AT values of three films were in the order of f-MPT>f-GPT>f-VPT due to complete-cage structures of building blocks (POSS) and the size of organic branches covalently bonded to the silica network in the molecular structures. This indicates that VPT powder might be significantly better to selected for the sun protection factor (SPF). Lower mtransparency of the films containing 30 wt-% TTB fractions is ascribed to more amounts of TTB in the modified films.
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Airoldi, C., V. Martire, M. S. Gálvez Elkin, P. Girard Bosch, V. Duarte, S. Scarafia, F. Sommerfleck et al. „POS0933 TREATMENT ACCESS AND ADHERENCE DURING SOCIAL PREVENTIVE AND MANDATORY ISOLATION IN ARGENTINIAN PATIENTS WITH SPONDYLARTHRITIS“. Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 730.1–730. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3147.
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Background:Access to high-cost treatments is especially limited in low-resource countries. This issue is becoming stronger today given the health and economic crisis caused by the SARS-CoV2 pandemic. There are no reports in our country on limitations to access and adherence to treatment in patients with Spondyloarthritis (SpA) during social preventive and mandatory isolation.Objectives:Evaluate access and adherence to treatment in patients with Spondyloarthritis during social preventive and mandatory isolation.Methods:Patients with axial spondyloarthritis (axSpA) radiological (r-axSpA), non-radiological (nr-axSpA) and peripheral spondyloarthritis (pSpA), according to ASAS criteria and psoriatic arthritis (PsA) according to CASPAR criteria, were included. Sociodemographic data, comorbidities, disease activity and treatments were collected at baseline. Data on treatment discontinuation, medical attention for suspected COVID-19 disease, RT-qPCR for SARS-CoV-2 detection and outcome of COVID-19 disease were collected from April to September 2020. Numerical variables were summarized as means and standard deviations (SD) or as medians and interquartiles 25-75 (IQ 25-75).Results:320 patients were included, 55% were male, with a mean age of 50 years (SD 13), 21.6% had diagnosis of r-axSpA, 6.9% nr-axSpA, 6.9% pSpA, and 64.7% PsA. Disease duration was 11 (IQ 5-16) years and activity parameters were as follow: BASDAI 3.65 (SD 3), BASFI 3 (1.5-9), PASI 0.3 (0-7), BSA 0.2 (0-6). 14 (4.4%) patients with COVID-19 disease were reported, 10 were confirmed by positive RT-qPCR and 4 by symptoms and history of close contact with SARS patients. 4 (28.6%) received anti TNF (3 adalimumab, 1 certolizumab), 4 (28.6%) anti IL17 (3 secukinumab and 1 ixekizumab), 8 (57%) methotrexate (MTX) and 2 (14%) leflunomide (LF). Among the 320 patients included, 59 (18.4%) discontinued at least one treatment during follow-up. The discontinued medications were: adalimumab (16), MTX (15), secukinumab (9), etanercept (6), certolizumab(4), ustekinumab (3), NSAIDs (2), apremilast (1), golimumab (1), ixekuzumab (1), LF (1), MTX plus LF (1). The main reason for treatment discontinuation was drug shortage: 36 (62%), followed by patient’s decision: 12 (21%) and medical indication: 11 (17%). Of the 36 patients who discontinued due to shortage, 11 received adalimumab, 8 secukinumab, 5 MTX, 3 etanercept, 3 certolizumab, 3 ustekinumab, 2 NSAIDs and 1 golimumab.Conclusion:In our Argentinian cohort of patients with SpA, drug shortage was the main reason for treatment discontinuation. The SARS-CoV2 pandemic exposed limitations to access to treatment for patients with SpA.Disclosure of Interests:None declared
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Schmeissner, T., R. Krejci, J. Ström, W. Birmili, A. Wiedensohler, G. Hochschild, J. Gross, P. Hoffmann und S. Calderon. „Analysis of number size distributions of tropical free tropospheric aerosol particles observed at Pico Espejo (4765 m a.s.l.), Venezuela“. Atmospheric Chemistry and Physics 11, Nr. 7 (07.04.2011): 3319–32. http://dx.doi.org/10.5194/acp-11-3319-2011.
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Abstract. The first long-term measurements of aerosol number and size distributions in South-American tropical free troposphere (FT) were performed from March 2007 until March 2009. The measurements took place at the high altitude Atmospheric Research Station Alexander von Humboldt. The station is located on top of the Sierra Nevada mountain ridge at 4765 m a.s.l. nearby the city of Mérida, Venezuela. Aerosol size distribution and number concentration data was obtained with a custom-built Differential Mobility Particle Sizer (DMPS) system and a Condensational Particle Counter (CPC). The analysis of the annual and diurnal variability of the tropical FT aerosol focused mainly on possible links to the atmospheric general circulation in the tropics. Considerable annual and diurnal cycles of the particle number concentration were observed. Highest total particle number concentrations were measured during the dry season (January–March, 519 ± 613 cm−3), lowest during the wet season (July–September, 318 ± 194 cm−3). The more humid FT (relative humidity (RH) range 50–95 %) contained generally higher aerosol particle number concentrations (573 ± 768 cm−3 during dry season, 320 ± 195 cm−3 during wet season) than the dry FT (RH < 50 %, 454 ± 332 cm−3 during dry season, 275 ± 172 cm−3 during wet season), indicating the importance of convection for aerosol distributions in the tropical FT. The diurnal cycle in the variability of the particle number concentration was mainly driven by local orography.
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Tong, Ming-Liang, Ji-Wen Cai, Xiao-Lan Yu, Xiao-Ming Chen, Seik Weng Ng und Thomas C. W. Mak. „Linear Metal(II)-4,4′-Bipyridine (4,4′-bpy) Chains Organized into Two-Dimensional Rhombic Networks by Hydrogen Bonding. Crystal Structures of [Co(4,4′-bpy)(H2O)4] (ClO4)2.(4,4′-bpy)2.2H2O and [Zn(4,4′-bpy)(H2O)3(ClO4)] (ClO4).(4,4′-bpy)1·5.H20“. Australian Journal of Chemistry 51, Nr. 7 (1998): 637. http://dx.doi.org/10.1071/c97207.
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Two substances with extended two-dimensional networks through hydrogen-bond cross linkages, namely, [Co(4,4′-bpy)(H2O4] (ClO4)2.(4,4′-bpy)2.2H2O and [Zn(4,4′-bpy)(H2O)3(ClO4)] (ClO4).(4,4′- bpy)1·5.H2O, were synthesized, in EtOH/H2O solution. The cobalt complex crystallizes in the triclinic space group P-1 with a 9·113(2), b 11· 093(2), c 11·394(2) Å, α 64·04(3), β 70·18(3), γ 66·91(3)°, V 932·9(3) Å3. The crystal structure contains 4,4′-bpy-bridged linear polymeric [Co(4,4′-bpy)(H2O)4]n chains, where the cobalt(II) is coordinated in a slightly distorted octahedral environment by four water molecules (Co-O 2·088(2)-2·101(2) Å) at the equatorial positions and two nitrogen atoms of the bridging 4,4′-bpy ligands (Co–N 2·149(2) Å) at the axial positions. The chains are interconnected into a two-dimensional rhombic network by double hydrogen-bond bridges of the type Co–H2O · · · bpy · · · H2O–Co. The zinc complex also crystallizes in the triclinic space group P-1 with a 9·0230(11), b 11·299(2), c 16·397(2) Å, α 74·429(11), β 83·132(9), γ 70·654(12)°, V 1518·5(3) Å3. The crystal structure contains 4,4′-bpy-bridged linear polymeric [Zn(4,4′-bpy)(H2O)3(ClO4)]n chains, where the zinc atom is coordinated in a distorted octahedral environment by two nitrogen atoms of the bridging 4,4′-bpy ligands (Z–N 2·104(2)–2·117(2) Å), three water molecules (Zn–O 2·068(2)–2·091(2) Å) and one monodentate ClO4- anion (Zn–O 2·320(2) Å). The chains are interconnected into a rhombic network alternately by single or double hydrogen-bond bridges of the type Zn–H2O · · · 4,4′-bpy · · · H2O–Zn.
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Pöschl, Sigrid. „Anne Brunner (2016) Schlüsselkompetenzen spielend trainieren. Berlin: De Gruyter. ISBN-Nummer: 978-3-11-040752-5; 320 Seiten; Preis: 39,95 €; E-Book: 39,95 €“. Spiritual Care 6, Nr. 1 (01.01.2017): 135–36. http://dx.doi.org/10.1515/spircare-2016-0198.
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Cheng, Y. F., H. Su, D. Rose, S. S. Gunthe, M. Berghof, B. Wehner, P. Achtert et al. „Size-resolved measurement of the mixing state of soot in the megacity Beijing, China: diurnal cycle, aging and parameterization“. Atmospheric Chemistry and Physics Discussions 11, Nr. 12 (07.12.2011): 32161–204. http://dx.doi.org/10.5194/acpd-11-32161-2011.
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Abstract. Soot particles are regarded as the most efficient light absorbing aerosol species in the atmosphere, playing an important role as a driver of global warming. Their climate effects strongly depend on their mixing state, which significantly changes their light absorbing capability and cloud condensation nuclei (CCN) activity. Therefore, knowledge about the mixing state of soot and its aging mechanism becomes an important topic in the atmospheric sciences. The size-resolved (30–320 nm diameter) mixing state of soot particles in polluted megacity air was measured at a suburban site (Yufa) during the CAREBeijing 2006 campaign in Beijing, using a Volatility Tandem Differential Mobility Analyzer (VTDMA). Particles in this size range with non-volatile residuals at 300 °C were considered to be soot particles. On average, the number fraction of internally mixed soot in total soot particles (Fin), decreased from 0.80 to 0.57 when initial Dp increased from 30 nm to 320 nm. Further analysis reveals that: (1) Fin was well correlated with the aerosol hygroscopic mixing state measured by a CCN counter. More externally mixed soot particles were observed when particles showed more heterogeneous features with regard to hygroscopicity. (2) Fin had pronounced diurnal cycles. For particles in the accumulation mode (Dp at 100–320 nm), largest Fin were observed at noon time, with apparent turnover rates (kex → in) up to 7.8% h−1. (3) Fin was subject to competing effects of both aging and emissions. While aging increases Fin by converting externally mixed soot particles into internally mixed ones, emissions tend to reduce Fin by emitting more fresh and externally mixed soot particles. Similar competing effects were also found with air mass age indicators. (4) Under the estimated emission intensities, actual turnover rates of soot (kex → in) up to 20% h−1 were derived, which showed a pronounced diurnal cycle peaking around noon time. This result confirms that (soot) particles are undergoing fast aging/coating with the existing high levels of condensable vapors in the megacity Beijing. (5) Diurnal cycles of Fin were different between Aitken and accumulation mode particles, which could be explained by the faster size shift of smaller particles in the Aitken mode. To improve the Fin prediction in regional/global models, we suggest parameterizing Fin by an air mass aging indicator, i.e., Fin = a + bx, where a and b are empirical coefficients determined from observations, and x is the value of an air mass age indicator. At the Yufa site in the North China Plain, fitted coefficients (a, b) were determined as (0.57, 0.21), (0.47, 0.21), and (0.52, 0.0088) for x (indicators) as [NOz]/[NOy], [E]/[X] ([ethylbenzene]/[m,p-xylene]) and ([IM] + [OM])/[EC] ([inorganic + organic matter]/elemental carbon]), respectively. Such a parameterization consumes little additional computing time, but yields a more realistic description of Fin.
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Alsaif, Manal, Joan Robinson, Moshtag Abdulbaqi, Mustafa Aghbari, Khalid Al Noaim und Muneera Alabdulqader. „PREVALENCE OF SERIOUS BACTERIAL INFECTIONS IN CHILDREN WITH SICKLE CELL DISEASE AT KING ABDULAZIZ HOSPITAL, AL AHSA“. Mediterranean Journal of Hematology and Infectious Diseases 13, Nr. 1 (31.12.2020): e2021002. http://dx.doi.org/10.4084/mjhid.2021.002.
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Aim: The main aim was to report the prevalence and severity of serious bacterial infections (SBI) in children with sickle cell disease at King Abdulaziz Hospital, Al Ahsa, Saudi Arabia to aid in determining whether outpatient management of such cases is appropriate.
Methods: We conducted a retrospective chart review of febrile children less than 14 years of age admitted with sickle cell disease 2005 through 2015.
Results: During 320 admissions, 25 children had SBIs (8%) including pneumonia (n=11), osteomyelitis (n=8), bacteremia (n=3, all with Salmonella species) and UTI (n=3). All recovered uneventfully.
Conclusion: It appears that in the current era, less than 10% of febrile children with sickle cell disease in our center are diagnosed with a SBI. Over an 11-year period, there were no sequelae or deaths from SBI. Given these excellent outcomes, outpatient ceftriaxone should be considered for febrile well appearing children with sickle cell disease if they have no apparent source and parents are judged to be reliable.
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Saliba, F., B. Paule, R. Adam, D. Castaing, D. Azoulay, I. Ogier, M. Pinel, V. Cadic und M. Delgado. „Vinflunine in patients with advanced unresectable hepatocellular carcinoma and liver impairment“. Journal of Clinical Oncology 25, Nr. 18_suppl (20.06.2007): 15023. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15023.
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15023 Background: In patients (pts) with advanced hepatocellular carcinoma (HCC) and liver cirrhosis, systemic chemotherapy has most commonly been associated with a very low response rate and high toxicity leading to death from liver failure. Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class which has demonstrated clinical activity in several tumour types. Methods: A phase I trial was designed to determine VFL dose adjustments in cancer pts with various degrees of liver dysfunction. A high number of pts with HCC and concomitant liver cirrhosis (Child-Pugh grades A and B) were included in the study (18/30 pts). Therefore, a subgroup analysis was carried out in order to determine the safety profile of VFL in these pts (NCI-CTC version 2.0) and to estimate its anti-tumour activity (WHO criteria). Results: Eighteen pts (15 males) of median age 60.7 [26.4–75.3] years with advanced stage and unresectable HCC were treated with VFL. All these pts were outside Milan criteria and ineligible for liver transplantation. Thirteen pts had been previously treated by chemotherapy. The WHO performance status was 0: 11 pts, 1: 5 pts, 2: 2 pts. They received a median number of 4 cycles [1.0–31.0] of different doses of VFL according to the severity of the underlying liver impairment 320 mg/m2 (3 pts), or 250 mg/m2 (6 pts) or 200 mg/m2 (9 pts). One partial response (PR) was observed while 11 pts (61.1%) had stable disease (SD) yielding a disease control rate (PR + SD) of 66.7%. The median progression free survival was 3.4 months [95% confidence interval (CI): 2.6–6.0]. Haematological toxicity: grades (G) 3 anaemia = 4 pts, G3/4 neutropenia = 11 pts, G3 thrombocytopenia = 7 pts, no febrile neutropenia. Other G3 toxicities included G3 abdominal pain (2 pts), constipation (3 pts), neutropenic infection (1 pt). Six pts experienced G3 (5 pts) or 4 (1 pt) fatigue. Conclusions: Vinflunine can be given safely at 320 mg/m2 or 250 mg/m2 or 200 mg/m2 in pts with unresectable advanced HCC with different degrees of liver impairment. The disease control rate is promising (66.7%). No significant financial relationships to disclose.
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Kolská, Zdeňka, Václav Švorčík und Jakub Siegel. „Size-dependent density of gold nano-clusters and nano-layers deposited on solid surface“. Collection of Czechoslovak Chemical Communications 75, Nr. 5 (2010): 517–25. http://dx.doi.org/10.1135/cccc2009537.
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The gold density enters some indirect determination of gold properties as an input parameter. Reported gold density of 19 320 kg m–3 at standard conditions is correct for gold bulk or macro-sized specimens. For nano-sized specimens (nano-clusters, nano-layers), however, this standard density value need not be applicable. This work deals with gold density as a function of the nano-structure size. The calculated density was compared with experimental one performed for gold sputtered onto glass or poly(ethylene terephthalate) substrates. Calculated gold density was found to increase from 11 249 to 19 304 kg m–3 when the characteristic dimension of gold nano-structures increases from 0.7 to 82 nm. At the same time the free volume fraction in nano-structures decreases from 57 to 26%.
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Duvic, Madeleine, Debra Breneman, Maureen Cooper, Gustavo Fonseca, J. Claude Bennett, J. Michael Kilpatrick und Shanta Bantia. „Phase I/II Study of Oral FodosineTM, a PNP Inhibitor in Refractory Cutaneous T-Cell Lymphoma Patients.“ Blood 106, Nr. 11 (16.11.2005): 2683. http://dx.doi.org/10.1182/blood.v106.11.2683.2683.
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Abstract Suppression of T-cell immunity seen in children with inherited purine nucleoside phosphorylase (PNP) deficiency supports the potential application of PNP inhibitors for the therapy of T-cell malignancies. Forodesine (FodosineTM) is a specific PNP inhibitor that raises plasma 2′-deoxyguanosine (dGuo) and intracellular dGTP levels, leading to T-cell apoptosis. IV administration of forodesine has shown activity in cutaneous T-cell lymphoma (CTCL) patients. To determine the safety, pharmacokinetics and pharmacodynamics of oral forodesine in patients with refractory CTCL, as well as preliminary evidence of efficacy, five cohorts of patients (≥ 3patients per cohort) were evaluated sequentially, receiving forodesine at 40, 80, 160, 320, and 480 mg/m2 once per day for 28 days. At the end of the treatment cycle (Day 28), all patients with stable or improved disease could enter a long-term, follow-up period. To date, 12 patients have been treated, 11 completing the 28-day cycle. Forodesine is orally absorbed (40%–50%), mean terminal half-life of 12 to 20 h. dGuo levels were elevated in all patients (0.8–2.8 μM, predose levels ≤ 0.004 μM). Forodesine was generally safe and well tolerated in this population. Safety data is available for first 7 patients. No serious adverse events possibly related to the drug occurred. The most common adverse event possibly drug related was nausea (2 patients). Of the 11 patients completing the treatment cycle, 9 began long-term treatment. Of these 9 patients, 4 have received >3 months of treatment, while 1 patient continues to receive for >8 months. Efficacy data are available for 8 patients: 2 with partial response, 3 with minor response, 2 with progressive disease, and 1 with stable disease (Table). Forodesine showed preliminary evidence of clinical activity in refractory CTCL patients. Additional clinical and pharmacodynamic data will be presented. Clinical and Pharmacodynamic Activity of Oral Forodesine In CTCL Patients Patient Diagnosis Dose (mg/m2) Treatment Plasma dGuo (Cmax, M) μ Clinical Response PR = partial response; MR = minor response; SD = stable disease; PD = progressive disease; N/A = not available 2001 Sezary syndrome (IVA) 40 Completed 0.6 PR 3001 Mycosis fungoides (IVB) 40 Completed 1.7 PD 3002 Mycosis fungoides (IIB) 40 Completed 1.2 MR 3003 Mycosis fungoides (IB) 80 Completed 1.2 MR 3004 Sezary syndrome (IVA) 80 Completed 1.0 MR 3005 Sezary syndrome 80 Completed 1.6 PD 2002 IIA 80 Completed 1.1 PR 2003 III 80 Completed 1.7 N/A 3006 Mycosis fungoides/Sezary syndrome (IVB) 160 Completed 2.8 SD 4001 III 320 Completed 1.8 N/A 1001 Mycosis fungoides (IB) 320 Completed 1.3 N/A 3012 Mycosis fungoides/Sezary syndrome (IVA vs B) 320 Not Completed N/A Not evaluable
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Negrea, O. George, Steven L. Allen, Kanti R. Rai, Rebecca Elstrom, Rashid Abassi, Charles M. Farber, Nick Teoh, Heather Horne, William A. Wegener und David M. Goldenberg. „Subcutaneous Injections of Low Doses of Humanized Anti-CD20 Veltuzumab for Treatment of Indolent B-Cell Malignancies.“ Blood 114, Nr. 22 (20.11.2009): 3757. http://dx.doi.org/10.1182/blood.v114.22.3757.3757.
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Abstract Abstract 3757 Poster Board III-693 Background Low IV doses of veltuzumab, a 2nd generation humanized anti-CD20 monoclonal antibody with structure-function differences from chimeric rituximab, have shown clinical activity in non-Hodgkin's lymphoma (Morschhauser et al., J Clin Oncol, 2009; 27:3346-53). By avoiding lengthy IV administration and the need for dedicated infusion suites, subcutaneous (SC) injections of low-dose veluzumab may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies, and this may be particularly useful in the setting of indolent disease. Methods A multicenter, phase I/II study was undertaken to evaluate the safety, tolerability, and preliminary efficacy of SC veltuzumab in previously untreated or relapsed CD20+ indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). All patients (pts) received 4 SC injections of veltuzumab 2 weeks apart at dose levels of 80, 160, or 320 mg. Efficacy was assessed by CT-based IWG (NHL) or hematology-based NCI/IWCLL (CLL) criteria 4 and 12 weeks later, with responding pts continuing follow-up. Other evaluations included AEs, safety laboratories, B-cell blood levels (CD19), serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Twenty-six pts (10M/16F, median age 64), including 15 NHL pts (12 follicular, 3 other indolent NHL; 5 treatment naïve) most with stage III or IV disease (12/15), and 11 CLL pts (4 treatment naïve) most with Rai stage II or III disease, have now received SC veltuzumab at 80 mg (3 NHL, 3 CLL), 160 mg (9 NHL, 3 CLL) or 320 mg (3 NHL, 5 CLL) dose levels. Pre-treatment with antihistamines or steroids was not required. SC veltuzumab was well tolerated with only mild, transient injection-site reactions and tenderness, and no other safety issues. To date, all HAHA response results have been negative. In NHL pts, SC veltuzumab demonstrated good bio-availability, with a slow release pattern over several days, and a mean Cmax of 18.7, 19.5 and 64.0 μg/mL at 80, 160, and 320 mg dose levels, respectively. Depletion of circulating B cells was observed starting after 1st injection. In the 15 NHL pts, the objective response rate (CR+CRu+PR) was 53% (8/15) with a complete response (CR) rate of 20% (3/15) and with 7/8 ORs currently continuing in remission, up to 6 months after treatment. The 11 CLL pts presented with mean white blood cell levels of 55K/μL (maximum 122K/μL) and achieved much lower serum veltuzumab levels, with mean Cmax values of 4.0, 2.5 and 21.0 μg/mL at the 80, 160, and 320 mg dose levels, respectively. There were no ORs, but 5 of 7 (71%) CLL pts with response assessments currently available showed stable disease with >70% decreases in B-cell levels for up to 12 weeks. Conclusions SC administration of veltuzumab is well tolerated, achieves slow but efficient delivery into the blood, and is pharmacologically active when given every 2 weeks for a total of 4 doses. In CLL with high levels of circulating leukemic cells, more frequent and prolonged dosing is likely required. However, in NHL, these low SC doses achieved sustained serum levels with objective response rates comparable to those seen even with higher IV doses. Disclosures: Negrea: Immunomedics: Research Funding. Off Label Use: veltuzumab for investigational treatment of NHL/CLL. Allen:Immunomedics: Research Funding. Rai:Immunomedics: Research Funding. Elstrom:Immunomedics: Research Funding. Abassi:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Teoh:Immunomedics: Employment. Horne:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.
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Harding, James J., James M. Cleary, David I. Quinn, Irene Braña, Victor Moreno, Mitesh J. Borad, Sherene Loi et al. „Targeting HER2 (ERBB2) mutation-positive advanced biliary tract cancers with neratinib: Results from the phase II SUMMIT ‘basket’ trial.“ Journal of Clinical Oncology 39, Nr. 3_suppl (20.01.2021): 320. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.320.
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320 Background: Genomic profiling studies have reported somatic HER2 mutations in ~2–5% of biliary tract cancers (BTC). Clinical data from the SUMMIT study demonstrate that neratinib, a pan-HER irreversible tyrosine kinase inhibitor, has encouraging clinical activity in multiple types of HER2-mutant solid tumor malignancies. Methods: SUMMIT is a multi-histology, open-label, phase II ‘basket’ study of neratinib in patients with somatic HER2 mutations (ClinicalTrials.gov NCT01953926). Patients with activating somatic HER2 mutations with different histologies, including BTC, received neratinib monotherapy (240 mg oral daily). Loperamide prophylaxis was mandatory during cycle 1. Efficacy endpoints: objective response rate (ORR, RECIST v1.1); clinical benefit rate (CBR); duration of response; progression-free survival (PFS). Adverse events (AEs) were assessed by CTCAE v4.0. Genomic profiling from fresh/archival tumor tissues and/or plasma cfDNA was performed retrospectively by next-generation sequencing (MSK-IMPACT). Results: As of 3-Sep-2020, 25 patients with HER2-mutant BTC were enrolled: gallbladder (40%); intrahepatic (24%); extrahepatic (20%); ampulla of Vater (16%). 68% of patients received ≥2 systemic regimens (96% received prior gemcitabine-based regimens). The S310F/Y variant accounted for nearly half of HER2 mutations (n=11). Other HER2 mutations: V777L (n=5); L755S (n=2); V842I (n=2); R678Q (n=2). Confirmed ORR in 25 evaluable patients was 12% (95% CI 3–31%) and CBR was 20% (95% CI 7–41%), including 3 confirmed PRs and 2 patients with SD for ≥16 weeks. Tumor shrinkage was observed in multiple HER2-activating mutations and enriched in gallbladder and extrahepatic subtypes of BTC. Median PFS was 2.8 (95% CI 1.1–3.7) months; median overall survival (OS) was 5.4 (95% CI 3.7–11.7) months. Nine (36%) patients (3 of whom with ECOG PS 2) came off study within 28 (range 6–47) days of treatment due to clinical deterioration (unrelated to study drug) followed by death. The most common treatment-related AEs (any grade) were diarrhea (56%) and vomiting (48%). Diarrhea was the most common Grade 3 event (24%); 4 patients (16%) required a neratinib dose reduction; no patients discontinued treatment due to diarrhea. Conclusions: Neratinib is safe and tolerable in patients with advanced BTC patients and somatic HER2 mutations. The antitumor activity of neratinib appears comparable to current standards of care, with similar PFS and OS in heavily pretreated patients. Analysis of co-occurring oncogenic mutations and response is ongoing, and consideration is being given to neratinib-based combination regimens to further improve outcomes in this setting. Clinical trial information: NCT01953926.
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Fontalvo, Mariana Campos, Isis Assis Braga, Daniel Moura Aguiar und Mauricio Claudio Horta. „SEROLOGICAL EVIDENCE OF EXPOSURE TO Ehrlichia canis IN CATS“. Ciência Animal Brasileira 17, Nr. 3 (September 2016): 418–24. http://dx.doi.org/10.1590/1089-6891v17i333845.
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Abstract The aim of the present study was to estimate the occurrence of Ehrlichia canis in cats from the semiarid region of Northeast of Brazil. Sera of 101 healthy cats were submitted by Indirect Immunofluorescence Assay (IFA), and considered positive when antibody titers ≥ 40 were obtained. Seroprevalence of 35.6% (36/101) was found, with the following titers: 40 (15 animals); 160 (6); 320 (1); 640 (3), and 2,560 (11). No statistical differences were observed when comparing county of origin, gender, age, breed, and modus vivendi (pet and stray cats), and no ticks were observed in any of the cats. This study revealed exposure to E. canis in cats of the Semiarid Northeast of Brazil.
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Hayakawa, Motoharu, Shingo Maeda, Akiyo Sadato, Teppei Tanaka, Takafumi Kaito, Natsuki Hattori, Tsukasa Ganaha et al. „Detection of Pulsation in Ruptured and Unruptured Cerebral Aneurysms by Electrocardiographically Gated 3-Dimensional Computed Tomographic Angiography With a 320-Row Area Detector Computed Tomography and Evaluation of Its Clinical Usefulness“. Neurosurgery 69, Nr. 4 (26.05.2011): 843–51. http://dx.doi.org/10.1227/neu.0b013e318225b2d3.
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Abstract BACKGROUND: In ruptured cerebral aneurysms (RCAs), identification of the rupture point of a cerebral aneurysm is useful for treatment planning. In unruptured cerebral aneurysms (URCAs), detection of the risk of aneurysmal rupture is also useful for patient management. OBJECTIVE: Electrocardiographic (ECG)-gated 3D-CT angiography was performed for patients with RCAs and URCAs using 320-row area detector CT (ADCT) to detect pulsation of the cerebral aneurysms. The clinical usefulness of this method was then evaluated. METHODS: Twelve patients had 12 RCAs, and 39 patients had 53 URCAs. A 320-row ADCT system was used to scan. ECG-gated reconstruction was then performed with the R-R interval divided into 20 phases. RESULTS: Pulsation was observed in 10 of the 12 RCAs. The bleeding site was considered to correspond to the area of pulsation. Pulsation was observed in 14 of 53 URCAs. Thirteen patients with 18 URCAs were followed. Of the 11 URCAs in which pulsation was not observed, 1 showed a change in shape. Of the 7 URCAs in which pulsation was observed, 3 showed a change in shape. URCAs in which pulsation was observed were more likely to show a change in shape (P = .082). CONCLUSION: The area of pulsation was found to correspond to the bleeding site in many RCAs. This information would be extremely useful for treatment planning. The detection of pulsation in an URCA is therefore considered to provide useful information for patient management.
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Allen, S. L., K. R. Rai, R. Elstrom, O. G. Negrea, C. M. Farber, R. Abbasi, N. Teoh, H. Horne, W. A. Wegener und D. M. Goldenberg. „Subcutaneous injections of low doses of veltuzumab (humanized anti-CD20 antibody): Objective responses in B-cell malignancies“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): 8530. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8530.
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8530 Background: Low IV doses of veltuzumab, a second-generation anti-CD20 monoclonal antibody with structure-function differences from chimeric rituximab, have shown clinical activity, thus justifying subcutaneous (SC) injections. Methods: A phase I/II study was initiated in patients (pts) with previously untreated or relapsed CD20+ indolent NHL or CLL who received 4 SC injections of veltuzumab 2 weeks apart at dose levels of 80, 160, or 320 mg. Efficacy was assessed by CT-based IWG (NHL) or hematology-based NCI/IWCLL (CLL) criteria 4 and 12 weeks later, with responding pts continuing follow-up. Other evaluations included AEs, safety laboratories, B-cell blood levels (CD19), serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results: Nineteen pts (8M/11F, median age 63), including 14 NHL pts (11 follicular, 3 other indolent NHL; 5 treatment naive) most with stage III or IV disease (11/14) and 5 CLL pts (4 treatment naïve) all with Rai stage II or III disease, have now received SC veltuzumab at 80 mg (3 NHL, 3 CLL), 160 mg (9 NHL, 2 CLL) or 320 mg (2 NHL) dose levels. Pre-treatment with antihistamines or steroids has not been required, and SC veltuzumab was well tolerated with only mild, transient injection site reactions and tenderness. To date, all HAHA results have been negative. In NHL pts, SC veltuzumab demonstrates good bio-availability, with a slow release pattern over several days and depletion of circulating B cells starting after 1st injection. Initial response information is currently available for 10 pts. For 7 NHL pts, 4 weeks after treatment with 80 or 160 mg doses, 2 pts had partial responses, 3 pts showed stable disease, and 2 pts had disease progression. For 3 CLL pts who received 80 mg doses, serum veltuzumab levels were lower, but all pts still achieved 65–75% decreases in circulating leukemic cells over the course of treatment. Conclusions: SC administration of veltuzumab is well tolerated, achieves slow but efficient delivery into the blood, and is pharmacologically active. The low doses currently evaluated in B-cell malignancies show evidence of therapeutic activity, achieving objective responses in NHL and notable reductions in circulating leukemic cells in CLL. [Table: see text]
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Chadwick, Owen. „Theologische Realenzyklopädie, 15. Heinrich H.-Ibsen. Edited by Gerhard Müller. Pp. 808 + plates. Berlin: Walter de Gruyter, 1986. DM 320. 3 11 008585 2“. Journal of Ecclesiastical History 39, Nr. 1 (Januar 1988): 157. http://dx.doi.org/10.1017/s002204690003949x.
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Chadwick, Owen. „Theologische Realenzyklopädie, xiv. Gottesdienst–Heimat. Edited by Gerhard Müller. Pp. 804 + 39 ills, and 3 maps. Berlin–New York: Walter de Gruyter, 1985. DM 320. 3 11 008583 6“. Journal of Ecclesiastical History 37, Nr. 4 (Oktober 1986): 664–65. http://dx.doi.org/10.1017/s0022046900022442.
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Kataoka, Akihisa, Kwanghow Lee, Masae Uehara und Nobusada Funabashi. „AORTIC VALVE AREA IN SUBJECTS WITH AORTIC VALVE STENOSIS BY 320-SLICE CT COMPARED WITH CONTINUOUS WAVE DOPPLER BY TRANSTHORACIC ECHOCARDIOGRAM CONSIDERING AORTIC VALVE CALCIFICATION AND LEFT VENTRICULAR EJECTION FRACTION“. Journal of the American College of Cardiology 57, Nr. 14 (April 2011): E1408. http://dx.doi.org/10.1016/s0735-1097(11)61408-3.
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Ko, Leta, Michael B. Lilly, Andrew W. Hahn, Roberto Nussenzveig, Marcus Marie Moses, Elisa Ledet, Charlotte Manogue et al. „Genomic changes of AR in ctDNA prior to enzalutamide in men with mCRPC after abiraterone acetate.“ Journal of Clinical Oncology 37, Nr. 7_suppl (01.03.2019): 320. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.320.
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320 Background: Approximately 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC) seem to respond to enzalutamide (ENZA) after prior exposure to abiraterone acetate and steroids (AA). The impact of genomic changes in androgen receptor (AR) gene in ctDNA and subsequent response to ENZA after prior AA exposure, is not entirely known. Methods: We performed a retrospective analysis of 28 mCRPC who were treated with ENZA after prior exposure to AA. Patients had NGS testing of ctDNA (Guardant 360) done post-AA and prior to ENZA. AR changes were defined by either amplification (amp; copy number ≥1) and/or mutations (mut; allele fraction ≥0.3%) in the AR gene. The primary endpoint of this study was time to PSA progression on enzalutamide. Correlations between genomic data and clinical outcomes were evaluated. Results: The 28 mCRPC patients had a median age of 67 (47-86), and 66.7% had a Gleason score 8-10. Metastases were found in bone (93%), lymph nodes (35.7%) and viscera (35%). Patients received ENZA after a median of 1 (1-5) treatment for CRPC. Patients were treated with prior AA for a median of 11.0 months (1.2-51.9) and median initial PSA at time of ENZA initiation was 35 ng/mL (1.52-356). The median time from ctDNA testing to ENZA start date was 0.9 months (range 0-5.6). Somatic changes in AR genes were detected in 36% (5/10 AR amp, 4/10 AR mut, 1/10 both). Other common alterations included 39% TP53, 11% DNA repair genes (2/3 BRCA2, 1/3 ATM), 7% PTEN. With a median follow-up of 8.9 months, 32% achieved PSA response (≥50%) and median time to PSA progression was 1.6 months (95% CI 1.0-2.2). On univariate analysis, lower Gleason scores (p = 0.021) and lack of AR changes (p = 0.042) were associated with PSA response to ENZA. Conclusions: In this cohort, responses to ENZA were associated with the absence of AR changes in ctDNA and less aggressive phenotypes. Prospective validation of this genomic association is required.
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Tkach, V. P., N. Yu Vysotska und O. V. Kobets. „Ріст і продуктивність порослевих осичників у свіжих і вологих грудах рівнинної частини України“. Forestry and Forest Melioration, Nr. 135 (25.03.2020): 41–49. http://dx.doi.org/10.33220/1026-3365.135.2019.41.
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За результатами аналізу повидільної бази даних ВО «Укрдержліспроект» змодельовано хід росту модальних порослевих осикових насаджень свіжого та вологого груду за природними зонами. Встановлено, що модальні порослеві осичники у грудових типах лісорослинних умов ростуть за І класом бонітету, а їхній запас у 70-річному віці сягає 345 м3·га-1 у Поліссі, 320 м3·га-1 у Лісостепу та 270 м3·га-1 у Степу. Підтверджено, що деревостани свіжих і вологих грудів є продуктивнішими, ніж деревостани у відповідних гігротопах сугрудових типів лісорослинних умов. Визначено різницю між запасами деревостанів сугрудів і грудів. В умовах Східного Полісся вона становить 1–2 %, в умовах Лісостепу збільшується до 11–15 %, а у Степу становить 3–9 %. Визначено вік кількісної стиглості осикових насаджень, який в обох типах лісорослинних умов становить 25–30 років.
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Goetz, Matthew P., Charles Erlichman, Anthony J. Windebank, Joel M. Reid, Jeffrey A. Sloan, Pamela Atherton, Alex A. Adjei et al. „Phase I and Pharmacokinetic Study of Two Different Schedules of Oxaliplatin, Irinotecan, Fluorouracil, and Leucovorin in Patients With Solid Tumors“. Journal of Clinical Oncology 21, Nr. 20 (15.10.2003): 3761–69. http://dx.doi.org/10.1200/jco.2003.01.238.
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Purpose: We sought to determine the maximum-tolerated dose (MTD) and evaluate the toxicities and clinical activity of two irinotecan (CPT-11), fluorouracil (FU), leucovorin (LV), and oxaliplatin schedules in patients with advanced solid tumors. Additionally, we investigated the effect of CPT-11 on oxaliplatin pharmacokinetics. Patients and Methods: Thirteen patients (cohort 1) received intravenous CPT-11 (infusion) and FU/LV (bolus) on days 1, 8, 15, and 22 and oxaliplatin (infusion) on days 1 and 15 every 6 weeks for a total 37 courses (median, three courses) at three dose levels. Twenty-two cohort 2 patients received intravenous CPT-11/oxaliplatin (infusion, day 1) and FU/LV (90-minute bolus infusion, days 2 to 5) every 3 weeks for a total of 122 courses (median, four courses) at three dose levels. Pharmacokinetic and neurotoxicity assessments were performed at the cohort 2 MTD. Results: Dose-limiting toxicity (DLT) seen in both cohorts at the starting dose required dose de-escalation. Cohort 1 DLT included diarrhea and neutropenia. In cohort 2, diarrhea, vomiting, dehydration, neutropenia, febrile neutropenia, and paresthesias were DLTs. Antitumor activity was seen in both cohorts. In cohort 2, the total platinum area under the curve of patients increased 17% in cycle 2 (P = .048), but objective neurotoxicity was not seen. Conclusion: The toxicities resulting from the addition of oxaliplatin to CPT-11/FU/LV are significant but manageable. The MTDs for the weekly schedule are CPT-11 (75 mg/m2), oxaliplatin (50 mg/m2), FU (320 mg/m2), and LV (20 mg/m2); and, for the 3-weekly schedule, the MTDs are CPT-11 (175 mg/m2), oxaliplatin (85 mg/m2), FU (240 mg/m2), and LV (20 mg/m2). Second-cycle platinum accumulation raises the possibility for enhanced cumulative neurotoxicity with CPT-11/oxaliplatin combinations.
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Kubacheva, K. K., L. Velikanova, N. V. Vorokhobina und P. A. Silnitskii. „The functional state of pituitary-adrenal system in the adolescents and younger males with hy-pertension“. "Arterial’naya Gipertenziya" ("Arterial Hypertension") 15, Nr. 3 (28.06.2009): 320–24. http://dx.doi.org/10.18705/1607-419x-2009-15-3-320-324.
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Objective. To evaluate the functional condition of pituitary-adrenal system of juveniles and young men with hypertension. Design and methods. 87 juveniles with obesity (including only 69 with hypertension) and 24 normal weight juveniles with hypertension were examined. Results. The laboratory criteria of subclinical Cushing's syndrome and congenital adrenal hyperplasia with 11-β-hydroxylase failure with corticosteroid identification in blood and urine by high-efficiency liquid chromatography at dexamethasone and corticotropin tests were developed.
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Strakova, Z., und M. S. Soloff. „Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction“. American Journal of Physiology-Endocrinology and Metabolism 272, Nr. 5 (01.05.1997): E870—E876. http://dx.doi.org/10.1152/ajpendo.1997.272.5.e870.
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Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial membranes with iodinated oxytocin antagonist (OTA), followed by detergent solubilization and size selection, showed that radioactivity eluted in two distinct peaks: one corresponding in size to the isolated receptor (approximately 60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT) increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold in a dose-dependent manner. The effects of OT were blocked by coincubation with OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak were identified by immunoadsorption. Significant amounts of both G alpha q/11 and G alpha i3 were associated with the OTR; a lesser amount of G alpha s was complexed. Using the same approach but with antibodies to effector enzymes, we observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated with the OTR. The results corroborate the well-established interaction of OTR with Gq and further show that Gi coupling might be an important component of OTR signal transduction. To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT treatment. These findings with pertussis toxin strongly indicate that OTR is coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled receptor) was demonstrable in the myometrium only before the end of gestation and after parturition and accounted for about one-half the 125I-OTA binding activity. At term, there was about a fivefold increase in binding and almost a complete shift to the 240- to 320-kDa-size complex. Thus the established increased sensitivity of the myometrium to OT at term could be the result of both upregulation of OTRs and an increase in the fraction of receptors coupled to signal transduction components, one of which is Gi.
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Wong, K. K., P. M. Fracasso, R. M. Bukowski, P. N. Munster, T. Lynch, R. Abbas, S. E. Quinn, C. Zacharchuk und H. Burris. „HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: Preliminary phase 1 results in patients with solid tumors“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 3018. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.3018.
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3018 Background: HKI-272 is a potent, low molecular weight, orally active, irreversible pan erbB receptor tyrosine kinase inhibitor. It inhibits the growth of tumor cells that express erbB-1 (epidermal growth factor receptor, EGFR) and erbB-2 (HER-2) in culture and xenografts. HKI-272 also inhibits the growth of cultured cells that contain sensitizing and resistance-associated EGFR mutations (Kwak et al, Proc Natl Acad Sci USA 102:7665–70, 2005). We are conducting a phase 1 study in patients (pts) with advanced-stage tumors that express EGFR or HER-2 to assess HKI-272 for tolerability, safety, pharmacokinetics, and preliminary antitumor activity. Methods: Pts (3–6/cohort) received 40, 80, 120, 180, 240, 320, or 400 mg HKI-272 orally once on day 1 and then once daily beginning on day 8. Timed blood samples were collected on days 1 and 21 for pharmacokinetic analysis. Results: Enrollment of 73 pts is complete. Preliminary data for 51 pts as of 28 Nov 2005 are presented. Patients were a median 60 years and 26% men. The most frequently occurring tumor types at primary diagnosis were breast (23 pts), non-small cell lung (9), and colorectal, ovarian, and renal (3 pts each). Dose escalation ended when 2 pts who received 400 mg HKI-272/day had drug-related dose-limiting toxicity of grade 3 diarrhea. Thus, the maximum tolerated dose (MTD) was 320 mg HKI-272/day. HKI-272-related adverse events (AEs), any grade, that occurred in ≥10% of pts were diarrhea (84%), nausea (55%), asthenia (45%), anorexia (31%), vomiting (29%), chills (12%), and rash (10%). Grade 3 related AEs that occurred in >1 pt were diarrhea (11) and asthenia (4). HKI-272 Cmax and AUC increased in a dose-dependent manner. At steady state at the MTD, mean values were Cmax: 112±58 ng/mL, AUC: 1618±930 ng.h/mL, t1/2: 15±2.5 h. Day 1 and 21 AUC values were comparable. Tumor assessments (modified RECIST criteria) were made at baseline and at the end of alternate cycles (28 days/cycle). Two breast cancer pts had confirmed partial responses (PRs) and 2 had unconfirmed PRs. Conclusions: When HKI-272 was administered on a continuous, once-daily, oral treatment schedule, the MTD was 320 mg/day, with diarrhea as the most frequently occurring related AE. HKI-272 has antitumor activity in HER-2-positive breast cancer. [Table: see text]
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Promboon, Amornrat, Toru Shimada, Haruhiko Fujiwara und Masahiko Kobayashi. „Linkage map of random amplified polymorphic DNAs (RAPDs) in the silkworm, Bombyx mori“. Genetical Research 66, Nr. 1 (August 1995): 1–7. http://dx.doi.org/10.1017/s0016672300034339.
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SummaryWe have constructed a linkage map of random amplified polymorphic DNAs (RAPDs) in Bombyx mori. We screened 320 10-mer primers, and found 243 clear polymorphic bands between C108 and p50 strains. In the F2 generation, segregation ratios of 168 bands were nearly 3:1 in a chi square test, showing Mendelian inheritance. The MAPMAKER program sorted 168 bands into 29 linkage groups and 10 unlinked loci at minimum LOD score 3·0, and determined orders of loci in each group, which contained 2–11 markers. It also detected typing errors in our data. We calculated map distances between pairs of neighbouring loci using recombination values in males and the Kosambi mapping function. Our RAPD map consists of 169 loci including the p locus, and the sum of map distances is approximately 900 cM. Linkage groups 1 and 2 of our map correspond to chromosomes 1 and 2 on the conventional linkage map because of linkage to sex and p, respectively.
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Korokin, M. V., V. O. Soldatov, A. A. Tietze, M. V. Golubev, A. E. Belykh, M. V. Kubekina, O. A. Puchenkova et al. „11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.“ Pharmacy & Pharmacology 7, Nr. 6 (17.01.2020): 312–20. http://dx.doi.org/10.19163/2307-9266-2019-7-6-312-320.
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The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases.Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated.Results. Theresults of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO.Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases.
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Suleymanov, Sultan Khamidovich, Elman Sayad ogli Nabiev, Valery Grigorevich Dyskin, Mustafa Umerovich Djanklich, Oleg Andreevich Dudko und Natalya Aleksandrovna Kulagina. „THE STUDY OF TECHNOLOGICAL REGIMES OF HARDENING BANDAGE STEEL OF THE CONCENTRATED FLOW OF ENERGY“. Computational nanotechnology 6, Nr. 3 (30.09.2019): 11–15. http://dx.doi.org/10.33693/2313-223x-2019-6-3-11-15.
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The work is devoted to the development of technological modes of strengthening of the band steel of locomotive wheels by the method of thermal treatment with concentrated energy flow. Thermal treatment of the banding steel was carried out on a solar furnace at flow densities 320, 450 and 500 W/sm2. Quenching was carried out in air and water. Heating and cooling rates are important for quenching. If speed of cooling is less than critical speed ( V cr ≈ 50 deg/s), quenching is not observed. The hardness of the tempered steel samples after thermal treatment at a temperature of 800-1200°C and treated in water reaches ≈726 HB, that is not optimum for bandage steel.The optimum temperature for quenching the band steel is 730-780°C at a flow density of 450 W/sm2. At the heating temperature of the steel samples 730-780°C and cooling by quenching into water, the hardness of the band steel is the required value of 350-400 HB. By changing the heating temperature and cooling rate of the steel, a predetermined hardness can be controlled and obtained.
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Salazar, Ramon, Jan Willem de Waard, Bengt Glimelius, John Marshall, Joost Klaase, Jacobus Van Der Hoeven, Jaume Capdevila, Frédéric Bibeau, Lisette Stork-Sloots und Robert Rosenberg. „The PARSC trial, a prospective study for the assessment of recurrence risk in stage II colon cancer (CC) patients using ColoPrint.“ Journal of Clinical Oncology 30, Nr. 4_suppl (01.02.2012): 678. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.678.
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678 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying CC patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in in-silico datasets and independent patient cohorts of stage II and III patients. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. ColoPrint identified two-third of the stage II patients (209/320) as low risk. The 3-year relapse-free survival was 94% for Low Risk patients and 79% for High Risk patients with a HR of 2.74 (95% CI 1.54 - 4.88; p=0.006). Moreover, the profile stratified patients independent of ASCO clinical risk factors. Methods: A prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II CC patients) using ColoPrint has been initiated. Objectives are: (1) to validate the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage II colon cancer; (2) to compare the risk assessment in stage II patients using the ColoPrint profile vs. a clinical risk assessment based on Investigator’s assessment of risk and ASCO high-risk recommendations; (3) to investigate therapy as a potential confounding factor for ColoPrint results; and (4) to assess the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage III colon cancer. Inclusion criteria: age ≥ 18 years, adenocarcinoma of the colon, stage II and III, no prior neo-adjuvant therapy, no synchronous tumors, fresh tumor sample, and written informed consent. The treatment of the patient is at the discretion of the physician adhering to National Comprehensive Cancer Network (NCCN)-approved regimens or a recognized alternative. Results: The trial started in Sept. 2008 with currently 30 participating sites in 11 countries. Thus far, 288 eligible stage 2 and 251 stage 3 patients have been enrolled. Conclusions: The aim is to enroll 575 stage II patients to differentiate between 3 year RFS predicted by ColoPrint and clinical factors.
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Grundy, H. F., K. P. A. Wheeler und R. Hardy. „Rapeseed meal, maize-gluten feed and fish meal as protein supplements for maize silage given to growing/finishing Limousin × Holstein Friesian bulls“. Animal Science 63, Nr. 2 (Oktober 1996): 223–28. http://dx.doi.org/10.1017/s1357729800014776.
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AbstractIn each of three experiments, 60 Limousin × Holstein Friesian bulls, initially of 191, (s..e. 5·0), 177 (s.e. 5·5) and 210 (s.e. 7·2) kg mean live weight for experiments 1, 2 and 3 respectively, were offered maize silage ad libitum plus one of three barley-based, isonitrogenous compound diets containing 200 g rapeseed meal, 575 g maize-gluten feed or 100 g fish meal per kg fresh weight. Compound diets were given at the rate of 3·0 kg (fresh weight) per head per day up to 320 kg live weight and at 3·3 kg per head per day from 320 kg to 420 kg live weight. In experiment 3, when bulls were taken through to slaughter, the compound diet was further increased to 3·5 kg per head per day from 420 kg live weight to slaughter. Experiments 1 and 2 were conducted over 128 and 194 days, with mean live weights at the end of the experiments of 347 (s.e. 17·2) and 414 (s.e. 24·2) kg respectively. In experiment 3, bulls were slaughtered at 16 months of age at a mean live weight of 544 (s.e. 25·0) kg.In experiment 1, the fish-meal diet gave the highest rate of daily live-weight gain at 1·34 compared with 1·17 and 1·16 (s.e.d. 0·041) kg for rapeseed-meal and maize-gluten diets, respectively. In experiments 2 and 3, daily gains were similar on all treatments at 1·21, 1·19 and 1·26 (s.e.d. 0·036) kg and 1·06, 1·09 and 1·11 (s.e.d. 0·035) kg for the rapeseed-meal, maize-gluten and fish-meal diets respectively. Total daily dry-matter intakes did not show consistent trends: in experiment 1, intakes were 5·8, 5·6 and 5·8 kg/day, in experiment 2, 6·2, 6·2 and 6·3 kg/day; and in experiment 3, 7·1, 7·3 and 7·1 kg/day for rapeseed-meal, maize-gluten and fish meal, respectively. The higher intakes of dry matter in experiment 3 were due to the greater intakes of maize silage by bulls taken to heavier weights in this experiment.
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Baselga, J., P. Schöffski, F. Rojo, H. Dumez, F. J. Ramos, T. Macarulla, R. Cajal, O. Kisker, A. Van Oosterom und J. Tabernero. „A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC)“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 3006. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.3006.
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3006 Background: C and G are two anti-EGFR agents with different mechanisms of action. We had previously shown a synergistic effect combining the two agents in preclinical models (Matar et al, Clin Cancer Res 2004). This study aims to explore safety, PK and PD changes in tumor and skin at different doses of C/G to define the recommended dose (RD) for further development. Methods: pts were treated at the RD of weekly iv C (400 mg/m2 initial dose, 250 mg/m2 weekly) and oral daily G (250 mg/d) as single agents (5 pts each) and in successive cohorts of combined C/G (3–6 pts each): C (320/200) / G (100), C (400/250) / G (100), C (400/250) / G (250), C (320/200) / G (500) & C (400/250) / G (500) (ongoing). Dose escalation depended on dose limiting toxicity (DLT) rate during the first 28 d. Pre- & on-treatment steady-state (14 d) tumor & skin biopsies were obtained and have been evaluated by IHC for total (t) and phospho (p)-EGFR, p-MAPK, p-Akt, proliferation (Ki67), p27 expression and apoptosis by TUNEL. Gene profiling analysis is ongoing. Results: 35 pts have been treated so far: 20 CRC, 13 HNC & 2 NSCLC; median KI 90 % (70–100); median age 60 years (38–80); 24 males, 11 females. DLTs occurred in 3 pts: 1 pt with G alone with reversible ILD; 1 pt with G (250) / C (400/250) with reversible deafness & 1 pt with G (500) / C (320/200) with grade 3 anorexia and nausea. There were 1 CR (HNC) and 5 PRs (CRC) in the C/G cohorts, and 1 PR (CRC) in the C cohort. Overall, 5 out of 9 (56%) pts with CRC treated in the C/G cohorts presented a PR. PD studies show superior inhibition of p-EGFR, p-MAPK and p-Akt, reduction of proliferation and increased apoptosis (all p values <0.05) in the tumors of pts treated with C/G compared with the single agent cohorts. PK evaluation shows no PK interactions with the 2 drugs. Conclusions: This combination of an anti-EGFR MAb (C) and a TKI (G) is feasible at the RD of both agents. Our findings show encouraging clinical activity, especially in CRC, and superior PD signaling inhibition with the combination without any significant PK interaction. Combined anti-EGFR therapy deserves further evaluation. [Table: see text]
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Elkiran, Omer, und Cumhur Avşar. „Chemical composition and biological activities of the essential oil from the leaves of Vaccinium myrtillus L.“ Bangladesh Journal of Botany 49, Nr. 1 (31.03.2020): 91–96. http://dx.doi.org/10.3329/bjb.v49i1.49098.
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The chemical composition, antimicrobial and antioxidant properties of the essential oil (EO), obtained from the leaves of Vaccinium myrtillus naturally grown in the northernmost of Turkey were determined by GC and GC-MS and chemical differences were discussed with the help of chemotaxonomy. The leaves of the plant samples were hydro-distilled to produce oil in the yields of 1%. Nineteen components were identified representing 96.4% of the oil. The main compounds in the EO of V. myrtillus were; 1,8-cineole (38.6%), α- pinene (21%), linalool (19.5%), α-terpineol (5.8%). The EO extract was screened for their antimicrobial activities against the 9 bacteria and 3 yeast species by using disc-diffusion and MIC procedure. The EO extract displayed more effective against all the tested bacteria (especially, S. aureus ATCC 6538 and MRSA) and yeast (only C. krusei). The MIC values of sample against tested microorganisms were found to be in the range of 320 to ≥1280 μg/ml. The most effective MIC values were observed against the S. aureus and MRSA (320 μg/ml). In vitro the antioxidant activity based on the 1,1-diphenly-2-picrylhydrazyl (DPPH) free radical was evaluated for the EO extract, and it was found that the extract had good antioxidant activity in the range of the IC50 = 583.4 ±11 μg ml. Antibacterial and antioxidant activities of the EO from the leaves of V. myrtillus has been reported for the first time.
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Kalaycio, Matt, O. George Negrea, Rebecca Elstrom, Charles Farber, Heather Horne, William A. Wegener und David M. Goldenberg. „Monotherapy with Subcutaneous (SC) Injections of Low Doses of Humanized Anti-CD20 Veltuzumab Is Active in Chronic Lymphocytic Leukemia (CLL)“. Blood 120, Nr. 21 (16.11.2012): 192. http://dx.doi.org/10.1182/blood.v120.21.192.192.
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Abstract Abstract 192 Background: Veltuzumab is a 2nd generation humanized anti-CD20 monoclonal antibody with structure-function differences and improved preclinical properties compared to chimeric rituximab. In non-Hodgkin lymphoma, 4 SC injections of low-dose veltuzumab administered every other week demonstrated clinical activity (Negrea et al., Haematologica 2011;96:567–73), comparable to that demonstrated earlier with low veltuzumab doses delivered intravenously (Morschhauser et al., J Clin Oncol, 2009;27:3346–53), but avoiding the need for lengthy IV administration and dedicated infusion suites. In CLL, with high levels of circulating leukemic cells, more frequent and prolonged veltuzumab dosing may be required, which was investigated. Methods: A multicenter, phase I/II study was undertaken to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of SC veltuzumab in patients with previously untreated or relapsed CD20+ CLL. Patients initially received the NHL dosing schedule with 4 doses administered every other week at 80, 160, or 320 mg (Cohort 1, cumulative dose range: 320 – 1280 mg). After protocol amendment, subsequent patients received 16 doses administered twice-weekly at levels of either 160 or 320 mg (Cohort 2, cumulative dose range: 2560 – 5120 mg). Evaluations included adverse events, routine safety assessments, CT scans, lymphocyte (ALC) and CD19+ B-cell blood levels, with serum veltuzumab levels and human anti-veltuzumab antibody (HAHA) titers measured by ELISA assays performed by the Sponsor. Efficacy was assessed by hematology-based NCI/IWCLL criteria 4 and 12 weeks post-treatment, with responding patients continuing follow-up until progression up to 2 years. Results: A total of 20 patients (10 males/10 females, 50 – 93 years old, 7.9 – 138.5 × 109/μL WBC) were entered in Cohorts 1 (N=11) and 2 (N=9). Thirteen patients were treatment naïve, while 7 had received 1–6 prior treatments (including a rituximab-containing regimen in 6 patients). Most patients had Rai intermediate risk scores (N=14) and presented with one or more B symptoms (N=16). Pre-treatment with antihistamines or steroids was not required before SC veltuzumab. Veltuzumab was well tolerated with only transient Grade 1–2 injection-site reactions. One patient developed bacterial meningitis and withdrew during treatment, while another patient with a complicated medical history developed malignant hypertension, transient ischemic attack, and pneumonia 6 months after treatment; no other SAEs or Grade 3–4 events occurred. One patient previously treated with rituximab had anti-veltuzumab antibodies at study entry; HAHA response results for the other patients have all been negative. Circulating leukemic cells decreased after treatment in all patients by 7.7 to 90.8%, with 13 patients having >50% decreases from baseline, and 3 patients achieving ALC values <4000 cells/μL. Consistent with high and widely varying baseline ALC levels (5 – 116 cells x109/μL), veltuzumab serum levels were often low and variable at all except the highest dose level, with mean Cmax values, respectively, of 1.8, 4.5, and 30.8 μg/mL at dose levels of 80, 160, or 320 mg in Cohort 1, and 36.2 and 199.5 μg/mL at dose levels of 160 and 320 mg in Cohort 2. By IWCLL criteria, 3 patients had partial responses (PR) (including 2 continuing relapse-free at 12 and 24 months) and 12 patients had stable disease (SD) as best response (most progressing within 12 weeks, but 4 remaining relapse-free for 6 – 12 months). Three patients progressed by first evaluation and 2 patients withdrew consent prior to any response assessment. As such, 15 (83%) of 18 evaluable patients achieved either PR or SD after treatment. Veltuzumab appeared active at all dose groups, and, despite increasing cumulative doses from 320 to 5120 mg delivered with these 5 dose groups, treatment responses and percent ALC decreases appeared similar regardless of dose level (80 vs. 160 vs. 320 mg) or dosing schedule (Cohort 1 vs. 2). Conclusions: In CLL, with high levels of circulating leukemic cells, SC administration of veltuzumab is convenient, well-tolerated, and shows evidence of single-agent pharmacologic activity across a variety of dose levels and dosing schedules. These results support further studies in CLL, including combining veltuzumab with chemotherapy or given as a maintenance regimen. Disclosures: Horne: Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.
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Kim, T., S. Sym, S. Lee, M. Ryu, J. Lee, H. Chang, H. Kim, J. Shin, Y. Kang und J. Lee. „A UGT1A1 genotype-directed phase I study of irinotecan (CPT-11) combined with fixed dose of capecitabine in patients with metastatic colorectal cancer (mCRC)“. Journal of Clinical Oncology 27, Nr. 15_suppl (20.05.2009): 2554. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2554.
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2554 Background: The risk of severe toxicity of CPT-11 can be in part explained by polymorphism of UGT1A1. The most common polymorphism in Whites is UGT1A1*28. UGT1A1*6 is another common polymorphism in Asians. We designed a phase I study to investigate UGT1A1 genotype-directed maximum tolerated dose (MTD) of CPT-11 plus fixed dose of capecitabine in patients (pts) with Korean mCRC. Methods: Pts with mCRC screened UGT1A1 genotyping (*28 and *6) and were stratified into one of 3 groups according to the number of defective allele (DA): 0 (none of *28 or *6 allele), 1(only one of *28 or *6 allele), and 2 (*28/*28, *6/*6, or double heterozygous for *28 and *6). The dose of CPT-11 was escalated as following: Level -I:200, I:240, II:280, III:320, IV: 350, V: 380 mg/m2 (IV, once every 3 weeks). Capecitabine (1,000 mg/m2 PO BID) was administered on days 2–15 every 3 weeks. Dose limiting toxicity (DLT) and pharmacokinetic analyses was determined at cycle 1. Results: Forty-two pts, median age 50 years, EOOG performance ≤1 were recruited: 0 DA group (18 pts), 1 DA (18), and 2 DA (6). In 0 DA group, two of six pts experienced DLT at 380 mg/m2 with grade III asthenia (1 pts) and febrile neutropenia (1). In 1 DA group, all of two pts experienced DLT at 380 mg/m2 with grade III asthenia. In 2 DA group, two of three pts experienced DLT at 240 mg/m2 with febrile neutropenia (1) and grade IV neutropenia (1). The MTD was defined as CPT-11 350 mg/m2 for pts with 0 and 1 DA group and CPT-11 200 mg/m2 for pts with 2 DA group, with capecitabine. Median SN-38G/SN-38 AUC was 10.45, 8.78, and 1.66 in pts with 0, 1, and 2 DA group, respectively. Conclusions: CPT-11 dosing by UGT1A1*28 and *6 genotypes is feasible in Korean pts with mCRC. A dose of CPT-11 350 mg/m2 IV for pts with 0 and 1 DA group and CPT-11 200 mg/m2 for pts with 2 DA group, with capecitabine every 3 weeks, is recommended for further study. [Table: see text] No significant financial relationships to disclose.
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Flury, S., A. Peutzfeldt und A. Lussi. „Influence of Surface Roughness on Mechanical Properties of Two Computer-aided Design/Computer-aided Manufacturing (CAD/CAM) Ceramic Materials“. Operative Dentistry 37, Nr. 6 (01.10.2012): 617–24. http://dx.doi.org/10.2341/11-391-l.
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SUMMARY The aim of this study was to evaluate the influence of surface roughness on surface hardness (Vickers; VHN), elastic modulus (EM), and flexural strength (FLS) of two computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic materials. One hundred sixty-two samples of VITABLOCS Mark II (VMII) and 162 samples of IPS Empress CAD (IPS) were ground according to six standardized protocols producing decreasing surface roughnesses (n=27/group): grinding with 1) silicon carbide (SiC) paper #80, 2) SiC paper #120, 3) SiC paper #220, 4) SiC paper #320, 5) SiC paper #500, and 6) SiC paper #1000. Surface roughness (Ra/Rz) was measured with a surface roughness meter, VHN and EM with a hardness indentation device, and FLS with a three-point bending test. To test for a correlation between surface roughness (Ra/Rz) and VHN, EM, or FLS, Spearman rank correlation coefficients were calculated. The decrease in surface roughness led to an increase in VHN from (VMII/IPS; medians) 263.7/256.5 VHN to 646.8/601.5 VHN, an increase in EM from 45.4/41.0 GPa to 66.8/58.4 GPa, and an increase in FLS from 49.5/44.3 MPa to 73.0/97.2 MPa. For both ceramic materials, Spearman rank correlation coefficients showed a strong negative correlation between surface roughness (Ra/Rz) and VHN or EM and a moderate negative correlation between Ra/Rz and FLS. In conclusion, a decrease in surface roughness generally improved the mechanical properties of the CAD/CAM ceramic materials tested. However, FLS was less influenced by surface roughness than expected.
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Melchers, Gunnel. „Nuria Hernández, Daniela Kolbe and Monika Edith Schulz, A comparative grammar of British English dialects: Modals, pronouns and complement clauses (Topics in English Linguistics 50.2). Berlin: Mouton de Gruyter, 2011. Pp. viii + 320. ISBN 978-3-11-024028-3, e-ISBN 978-3-11-024029-0.“ English Language and Linguistics 18, Nr. 1 (06.02.2014): 196–202. http://dx.doi.org/10.1017/s1360674313000348.
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HARVEY, G. „The satanism scare James T. Robinson, Joel Best and David G. Bromley (eds), New York, Aldine de Grayter, 1991, 320 pp. ISBN 3 11 013221 4, paperback, DM 49“. Religion 22, Nr. 3 (Juli 1992): 290–91. http://dx.doi.org/10.1016/0048-721x(92)90028-3.
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