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Feng, Qi, and Tony T. Y. Lin. "The analysis of VERITAS muon images using convolutional neural networks." Proceedings of the International Astronomical Union 12, S325 (October 2016): 173–79. http://dx.doi.org/10.1017/s1743921316012734.
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AbstractImaging atmospheric Cherenkov telescopes (IACTs) are sensitive to rare gamma-ray photons, buried in the background of charged cosmic-ray (CR) particles, the flux of which is several orders of magnitude greater. The ability to separate gamma rays from CR particles is important, as it is directly related to the sensitivity of the instrument. This gamma-ray/CR-particle classification problem in IACT data analysis can be treated with the rapidly-advancing machine learning algorithms, which have the potential to outperform the traditional box-cut methods on image parameters. We present preliminary results of a precise classification of a small set of muon events using a convolutional neural networks model with the raw images as input features. We also show the possibility of using the convolutional neural networks model for regression problems, such as the radius and brightness measurement of muon events, which can be used to calibrate the throughput efficiency of IACTs.
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Geng, Fu Quan, Zhi Gang Huang, Xuan Jie Ning, and Mao Fan Yang. "A Joint Improved Irregular Accumulate Concatenated Tree Coding and Frequency Hopping OFDM Modulation Scheme for Wireless Networks." Advanced Materials Research 902 (February 2014): 364–69. http://dx.doi.org/10.4028/www.scientific.net/amr.902.364.
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Joint channel coding and spread spectrum modulation technologies bring to wireless networks the tremendous amount of performance improvement, the elimination, and the mitigation of interference. This paper proposes an improved design for irregular accumulate concatenated tree (IACT) codes, which can be viewed as simply precoded by an accumulator. This class of codes belongs to the special turbo-like codes, which combines the advantages of fast encoder structures of turbo codes, and the advantages of parallel high-speed belief-propagation (BP) iterative decoding algorithm of low-density parity-check (LDPC) codes. The improved IACT codes can be coded via a Tanner graph. With these improved codes, we propose a joint IACT coding and frequency hopping orthogonal frequency division multiplexing (FH-OFDM) modulation scheme for wireless networks. We compare the performance of different coding bases such as the irregular concatenated tree (ICT) codes and turbo codes in the scheme by theoretical analysis and simulation. Numerical results are shown that the proposed scheme with these IACT codes has really good performance.
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Fiasson, A., F. Dubois, G. Lamanna, J. Masbou, and S. Rosier-Lees. "Optimization of multivariate analysis for IACT stereoscopic systems." Astroparticle Physics 34, no. 1 (August 2010): 25–32. http://dx.doi.org/10.1016/j.astropartphys.2010.04.006.
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Mohrmann, L., A. Specovius, D. Tiziani, S. Funk, D. Malyshev, K. Nakashima, and C. van Eldik. "Validation of open-source science tools and background model construction in γ-ray astronomy." Astronomy & Astrophysics 632 (December 2019): A72. http://dx.doi.org/10.1051/0004-6361/201936452.
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In classical analyses of γ-ray data from imaging atmospheric Cherenkov telescopes (IACTs), such as the High Energy Stereoscopic System (H.E.S.S.), aperture photometry, or photon counting, is applied in a (typically circular) region of interest (RoI) encompassing the source. A key element in the analysis is to estimate the amount of background in the RoI due to residual cosmic ray-induced air showers in the data. Various standard background estimation techniques have been developed in the last decades, most of them rely on a measurement of the background from source-free regions within the observed field of view. However, in particular in the Galactic plane, source analysis and background estimation are hampered by the large number of, sometimes overlapping, γ-ray sources and large-scale diffuse γ-ray emission. For complicated fields of view, a three-dimensional (3D) likelihood analysis shows the potential to be superior to classical analysis. In this analysis technique, a spectromorphological model, consisting of one or multiple source components and a background component, is fitted to the data, resulting in a complete spectral and spatial description of the field of view. For the application to IACT data, the major challenge of such an approach is the construction of a robust background model. In this work, we apply the 3D likelihood analysis to various test data recently made public by the H.E.S.S. collaboration, using the open analysis frameworks ctools and Gammapy. First, we show that, when using these tools in a classical analysis approach and comparing to the proprietary H.E.S.S. analysis framework, virtually identical high-level analysis results, such as field-of-view maps and spectra, are obtained. We then describe the construction of a generic background model from data of H.E.S.S. observations, and demonstrate that a 3D likelihood analysis using this background model yields high-level analysis results that are highly compatible with those obtained from the classical analyses. This validation of the 3D likelihood analysis approach on experimental data is an important step towards using this method for IACT data analysis, and in particular for the analysis of data from the upcoming Cherenkov Telescope Array (CTA).
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Albert, A., R. Alfaro, C. Alvarez, J. C. Arteaga-Velázquez, D. Avila Rojas, H. A. Ayala Solares, R. Babu, et al. "Detailed Analysis of the TeV γ-Ray Sources 3HWC J1928+178, 3HWC J1930+188, and the New Source HAWC J1932+192." Astrophysical Journal 942, no. 2 (January 1, 2023): 96. http://dx.doi.org/10.3847/1538-4357/ac8de3.
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Abstract The latest High Altitude Water Cherenkov (HAWC) point-like source catalog up to 56 TeV reported the detection of two sources in the region of the Galactic plane at galactic longitude 52° < ℓ < 55°, 3HWC J1930+188 and 3HWC J1928+178. The first one is associated with a known TeV source, the supernova remnant SNR G054.1+00.3. It was discovered by one of the currently operating Imaging Atmospheric Cherenkov Telescope (IACT), the Very Energetic Radiation Imaging Telescope Array System (VERITAS), detected by the High Energy Stereoscopic System (H.E.S.S), and identified as a composite SNR. However, the source 3HWC J1928+178, discovered by HAWC and coincident with the pulsar PSR J1928+1746, was not detected by any IACT despite their long exposure on the region, until a recent new analysis of H.E.S.S. data was able to confirm it. Moreover, no X-ray counterpart has been detected from this pulsar. We present a multicomponent fit of this region using the latest HAWC data. This reveals an additional new source, HAWC J1932+192, which is potentially associated with the pulsar PSR J1932+1916, whose γ-ray emission could come from the acceleration of particles in its pulsar wind nebula. In the case of 3HWC J1928+178, several possible explanations are explored, in an attempt to unveil the origins of the very-high-energy γ-ray emission.
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Vovk, I., M. Strzys, and C. Fruck. "Spatial likelihood analysis for MAGIC telescope data." Astronomy & Astrophysics 619 (November 2018): A7. http://dx.doi.org/10.1051/0004-6361/201833139.
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Context. The increase in sensitivity of Imaging Atmospheric Cherenkov Telescopes (IACTs) has lead to numerous detections of extended γ-ray sources at TeV energies, sometimes of sizes comparable to the instrument’s field of view. This creates a demand for advanced and flexible data analysis methods that are able to extract source information using the photon counts in the entire field of view. Aims. We present a new software package, “SkyPrism”, aimed at performing 2D (3D if energy is considered) fits of IACT data that possibly contain multiple and extended sources. The fits are based on sky images binned in energy. Although the development of this package was focused on the analysis of data collected with the MAGIC telescopes, it can further be adapted to other instruments, such as the future Cherenkov Telescope Array. Methods. We have developed a set of tools that in addition to sky images (count maps) compute the instrument response functions of MAGIC (effective exposure throughout the field of view, point spread function, energy resolution, and background shape) based on the input data, Monte Carlo simulations, and the pointing track of the telescopes. With this information, the package can perform a simultaneous maximum likelihood fit of source models of arbitrary morphology to the sky images providing energy spectra, detection significances, and upper limits. Results. We demonstrate that the SkyPrism tool accurately reconstructs the MAGIC point spread function, on- and off-axis performance as well as the underlying background. We further show that for a point source analysis with the MAGIC default observational settings, SkyPrism gives results compatible with those of the standard tools while being more flexible and widely applicable.
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Ivanova, A. L., R. Monkhoev, I. Astapov, P. Bezyazeekov, M. Blank, E. Bonvech, A. Borodin, et al. "Tunka-Grande scintillation array: resent results." Journal of Physics: Conference Series 2156, no. 1 (December 1, 2021): 012196. http://dx.doi.org/10.1088/1742-6596/2156/1/012196.
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Abstract Objectives of the TAIGA Astrophysical complex include the study of the flux of charged cosmic rays and diffuse gamma rays with energies above 100 TeV. This complex is located in the Tunka Valley about 50 km from Lake Baikal at the site of the Tunka-133 Cherenkov facility. TAIGA includes the TAIGA-HiSCORE wide-angle Cherenkov array, the network of Imaging Atmospheric Cherenkov Telescopes (TAIGA-IACT), the Tunka-Grande and TAIGA-Muon scintillation arrays. In this work, we present the results of an analysis of the joint events of the Tunka-Grande scintillation array and TAIGA-HiSCORE and Tunka-133 Cherenkov facilities. The results verify sufficient accuracy of the scintillation experiment for the hybrid study of mass composition of cosmic rays and gamma-hadron separation.
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BARTKO, H. "OBSERVATION OF GALACTIC SOURCES OF VERY HIGH ENERGY γ-RAYS WITH THE MAGIC TELESCOPE." Modern Physics Letters A 22, no. 29 (September 21, 2007): 2167–74. http://dx.doi.org/10.1142/s0217732307024309.
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The MAGIC telescope with its 17m diameter mirror is today the largest operating single-dish Imaging Air Cherenkov Telescope (IACT). It is located on the Canary Island La Palma, at an altitude of 2200 m above sea level, as part of the Roque de los Muchachos European Northern Observatory. The MAGIC telescope detects celestial very high energy γ-radiation in the energy band between about 50 GeV and 10 TeV. Since the autumn of 2004 MAGIC has been taking data routinely, observing various objects, like supernova remnants (SNRs), γ-ray binaries, Pulsars, Active Galactic Nuclei (AGN) and Gamma-ray Bursts (GRB). We briefly describe the observational strategy, the procedure implemented for the data analysis, and discuss the results of observations of Galactic Sources.
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Ikrama, Syeda. "An Empirical Study on the Performance of Micro and Small Enterprises and the Financial Planning Managerial Practices." SEDME (Small Enterprises Development, Management & Extension Journal): A worldwide window on MSME Studies 46, no. 4 (December 2019): 248–55. http://dx.doi.org/10.1177/0970846419894755.
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This research paper is intended to study the performance of micro and small enterprises and the financial planning practices adopted by these enterprises. Financial planning means enabling the enterprise to have the right amount of capital in order that the business operations would not get affected. The businesses must first ascertain the financial objectives of the firm to formulate the policies relating to borrowing and lending, cash control, cash management, inventory management, and credit risk management and other financial activities. The present study is an analytical study and a random sampling technique is used. For the purpose of the study Hyderabad district is chosen and a sample size of 120 micro and small enterprises was taken. The statistical tools used for this study are Spearman Rank correlation, KMO Bartlett’s test and Factor analysis. The results of factor analysis gave two factors to ten variables—Important Aspects of Corporate Taxes (IACT) and Recording Transactions and Credit policy (RTCP).
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López-Coto, Rubén, Juan Cortina, and Abelardo Moralejo. "MACHETE: A transit Imaging Atmospheric Cherenkov Telescope to survey half of the Very High Energy γ-ray sky." Proceedings of the International Astronomical Union 11, A29A (August 2015): 345–46. http://dx.doi.org/10.1017/s1743921316003240.
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AbstractCurrent Cherenkov Telescopes for VHE gamma ray astrophysics are pointing instruments with a field of view up to a few tens of deg2. We propose to build an array of two non-steerable telescopes with a FoV of 5×60 deg2 oriented along the meridian. Roughly half of the sky drifts through this FoV in a year. We have performed a MC simulation to estimate the performance of this instrument, which we dub MACHETE. The sensitivity that MACHETE would achieve after 5 years of operation for every source in this half of the sky is comparable to the sensitivity that a current IACT achieves for a specific source after a 50 h devoted observation. The analysis energy threshold would be 150 GeV and the angular resolution 0.1 deg. For astronomical objects that transit over MACHETE for a specific night, it would achieve an integral sensitivity of 12% of Crab in a night. This makes MACHETE a powerful tool to trigger observations of variable sources at VHE or any other wavelengths.
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Neronov, A., and D. Semikoz. "Mapping large-scale diffuse γ-ray emission in the 10−100 TeV band with Cherenkov telescopes." Astronomy & Astrophysics 637 (May 2020): A44. http://dx.doi.org/10.1051/0004-6361/202037608.
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Context. Measurement of diffuse γ-ray emission from the Milky Way with Imaging Atmospheric Cherenkov Telescopes (IACT) is difficult because of the high level of charged cosmic ray background and the small field of view. Aims. We show that such a measurement is nevertheless possible in the energy band 10−100 TeV. Methods. The minimal charged particle background for IACTs is achieved by selecting the events to be used for the analyses of the cosmic ray electrons. Tight cuts on the event quality in these event selections allow us to obtain a sufficiently low background level to allow measurement of the diffuse Galactic γ-ray flux above 10 TeV. We calculated the sensitivities of different types of IACT arrays for the Galactic diffuse emission measurements and compared them with the diffuse γ-ray flux from different parts of the sky measured by the Fermi Large Area Telescope below 3 TeV and with the astrophysical neutrino signal measured by IceCube telescope. Results. We show that deep exposure of existing IACT systems is sufficient for detection of the diffuse flux from all the Galactic Plane up to Galactic latitude |b| ∼ 5°. The Medium Size Telescope array of the CTA will be able to detect the diffuse flux up 30° Galactic latitude. Its sensitivity will be sufficient for detection of the γ-ray counterpart of the Galactic component of the IceCube astrophysical neutrino signal above 10 TeV. We also propose that a dedicated IACT system composed of small but wide-field-of-view telescopes could be used to map the 10−100 TeV diffuse γ-ray emission from across the whole sky. Conclusions. Detection and detailed study of diffuse Galactic γ-ray emission in the previously unexplored 10−100 TeV energy range is possible with the IACT technique. This is important for identification of the Galactic component of the astrophysical neutrino signal and for understanding the propagation of cosmic rays in the interstellar medium.
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Franceschini, A., L. Foffano, E. Prandini, and F. Tavecchio. "Very high-energy constraints on the infrared extragalactic background light." Astronomy & Astrophysics 629 (August 22, 2019): A2. http://dx.doi.org/10.1051/0004-6361/201935617.
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Context. Measurements of the extragalactic background light (EBL) are a fundamental source of information on the collective emission of cosmic sources. Aims. At infrared wavelengths, however, these measurements are precluded by the overwhelming dominance from interplanetary dust emission and the Galactic infrared foreground. Only at λ > 300 μm, where the foregrounds are minimal, has the infrared EBL (IR EBL) been inferred from analysis of the COBE maps. The present paper aims to assess the possibility of evaluating the IR EBL from a few micrometers up to the peak of the emission at > 100 μm using an indirect method that avoids the foreground problem. Methods. To this purpose we exploit the effect of pair-production from gamma-gamma interaction by considering the highest-energy photons emitted by extragalactic sources and their interaction with the IR EBL photons. We simulate observations of a variety of low-redshift emitters with the forthcoming Imaging Atmospheric Cherenkov Telescope (IACT) arrays (CTA in particular) and water Cherenkov observatories (LHAASO, HAWC, SWGO) to assess their suitability to constrain the EBL at such long wavelengths. Results. We find that even under the most extremely favorable conditions of huge emission flares, extremely high-energy emitting blazars are not very useful for our purpose because they are much too distant (> 100 Mpc the nearest ones, MKN 501 and MKN 421). Observations of more local AGNs displaying very high-energy emission, like low-redshift radio galaxies (M 87, IC 310, Centaurus A), are better suited and will potentially allow us to constrain the EBL up to λ ≃ 100 μm.
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D’Amico, Giacomo. "Statistical Tools for Imaging Atmospheric Cherenkov Telescopes." Universe 8, no. 2 (January 29, 2022): 90. http://dx.doi.org/10.3390/universe8020090.
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The development of Imaging Atmospheric Cherenkov Telescopes (IACTs) unveiled the sky in the teraelectronvolt regime, initiating the so-called “TeV revolution”, at the beginning of the new millennium. This revolution was also facilitated by the implementation and adaptation of statistical tools for analyzing the shower images collected by these telescopes and inferring the properties of the astrophysical sources that produce such events. Image reconstruction techniques, background discrimination, and signal-detection analyses are just a few of the pioneering studies applied in recent decades in the analysis of IACTs data. This (succinct) review has the intent of summarizing the most common statistical tools that are used for analyzing data collected with IACTs, focusing on their application in the full analysis chain, including references to existing literature for a deeper examination.
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Zacharioudakis, Ioannis, Fainareti Zervou, Fadi Shehadeh, Eleftherios Mylonakis, and Eleftherios Mylonakis. "658. Cost-effectiveness of Molecular Diagnostic Assays for the Therapy of Severe Sepsis and Septic Shock in the Emergency Department." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S302. http://dx.doi.org/10.1093/ofid/ofz360.726.
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Abstract Background Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes.We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. Methods We developed a decision analysis model with the primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients’ length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described.Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. Results Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER −$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity ≥52%, panel efficiency ≥39%, and assay cost ≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained ≤$20,000/death averted for every studied sensitivity (i.e., 0.5–0.95), panel efficiency ≥34%, and assay cost ≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was ≤$135 and the panel efficiency was ≥77%. Conclusion The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios. Disclosures Eleftherios Mylonakis, MD PhD, Sanofi-Pasteur: Grant/Research Support; T2 Biosystems: Grant/Research Support.
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Miksad, Rebecca A., Mithat Gönen, Thomas J. Lynch, and Thomas G. Roberts. "Interpreting Trial Results in Light of Conflicting Evidence: A Bayesian Analysis of Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer." Journal of Clinical Oncology 27, no. 13 (May 1, 2009): 2245–52. http://dx.doi.org/10.1200/jco.2008.16.2586.
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PurposeWhen successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods.MethodsThree recent non–small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR.10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability.ResultsThe probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR.10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit.ConclusionWhen evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR.10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
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Tang, Haiying, Joseph R. Vasselli, Ed X. Wu, Carol N. Boozer, and Dympna Gallagher. "High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 282, no. 3 (March 1, 2002): R890—R899. http://dx.doi.org/10.1152/ajpregu.0527.2001.
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Magnetic resonance imaging (MRI) has the ability to discriminate between various soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT), intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights determined by MRI were compared with weights determined by dissection and chemical analysis in two studies with male Sprague-Dawley rats. A 4.2-T MRI machine acquired high-resolution, in vivo, longitudinal whole body images of rats as they developed obesity or aged. Weights of the whole body and specific tissues were determined using computer image analysis software, including semiautomatic segmentation algorithms for volume calculations. High correlations were found for body weight ( r = 0.98), TAT ( r = 0.99), and IAAT ( r = 0.98) between MRI and dissection and chemical analyses. MRI estimated the weight of the brain, kidneys, and spleen with high accuracy ( r > 0.9), but overestimated IAAT, SM, and liver volumes. No differences were detected in organ weights using MRI and dissection measurements. Longitudinal MRI measurements made during the development of obesity and aging accurately represented changes in organ and tissue mass.
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Shi, Junyan, Pawan Dhaliwal, Yu Zi Zheng, Terry Wong, Joely A. Straseski, Mark A. Cervinski, Zahra Shajani-Yi, and Mari L. DeMarco. "An Intact ACTH LC-MS/MS Assay as an Arbiter of Clinically Discordant Immunoassay Results." Clinical Chemistry 65, no. 11 (November 1, 2019): 1397–404. http://dx.doi.org/10.1373/clinchem.2019.306365.
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Abstract BACKGROUND Measurement of plasma adrenocorticotropic hormone (ACTH) is key in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. Two-site sandwich immunoassays dominate clinical testing of ACTH in North America; however, discordant results between manufacturers have been repeatedly reported. To resolve the discrepancy, we developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay for the intended measurand, biologically active intact ACTH (iACTH). METHODS The multiple reaction monitoring LC-MS/MS assay was designed to selectively measure full-length iACTH, as well as ACTH analogs and fragments (i.e., ACTH1–24 and ACTH18–39). Epitope assignment of the Roche Elecsys antibodies was performed by MALDI-TOF mass spectrometry. A method comparison between Roche Elecsys and Siemens Immulite ACTH immunoassays was performed and clinically concordant/discordant results identified. In a subset of these samples, the iACTH concentration was determined using the LC-MS/MS method. RESULTS The lower limit of the measuring interval of the iACTH LC-MS/MS assay was 9 pg/mL (2 pmol/L). The assay was linear from 9 to 1938 pg/mL (2 to 427 pmol/L). Epitope mapping revealed that the Roche capture and detection antibodies bound residues 9–12 and 36–39 of ACTH, respectively. The iACTH LC-MS/MS analysis demonstrated that for discordant results between 2 immunoassays studied, only the Roche results were highly positively correlated with the iACTH concentration. CONCLUSIONS Immunoprecipitation of biologically active ACTH molecules followed by LC-MS/MS analysis enabled selective detection of iACTH and relevant biologically active fragments in plasma. Applied to the investigation of clinically discrepant results, this method can act as an arbiter of the concentration of iACTH present.
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Liu, Xi, Xiaofei Liu, Pinxuan Huang, Fang Wei, Guangyao Ying, Shuwei Zhang, Jinghua Lu, Lidong Zhou, and Weijun Kong. "Regeneration and Reuse of Immunoaffinity Column for Highly Efficient Clean-Up and Economic Detection of Ochratoxin A in Malt and Ginger." Toxins 10, no. 11 (November 8, 2018): 462. http://dx.doi.org/10.3390/toxins10110462.
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Immunoaffinity columns (IACs) are most popularly used for mycotoxin clean-up in complex matrices prior to chromatographic analysis. But, their high cost has limited their wide application and the regeneration of IACs for multiple instances of reuse is important. This study aimed to investigate the feasibility of regeneration and reuse of IACs for purification of ochratoxin A (OTA) in spiked raw malt and dried ginger samples followed by high performance liquid chromatography-fluorescence detection. After each use, the IACs were filled with phosphate buffer saline (PBS) as the preservation solution and stored at 8 °C overnight for regeneration and reuse until the recovery rate was <70%. The results showed that matrix type, preparation procedure, and pH value of sample extraction exhibited major effects on the reuse of IACs for OTA clean-up. While, after modifying the sample preparation procedure using water as the diluent and the solution at a pH of 7 to 8, the IACs could be used eight and three times for the spiked raw malt and dried ginger samples with OTA after regeneration. Regarding the traditional procedure recommended in Chinese Pharmacopoeia (2015 edition), the IACs could be used for three and two times for the spiked raw malt and dried ginger samples with OTA, respectively. Therefore, the corresponding experimental cost could be reduced to one-eighth and one-third of the original cost. This is the first study on the regeneration and reuse of IACs for OTA clean-up in complex Chinese herbal medicines, providing a green and economical tool for a large number of samples analysis with low cost.
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Shatry, Alwi, and Robert B. Levy. "Administration of IL-2-Anti-IL2mAb Complex Post-Allogeneic HCT: a New Approach to Facilitate Rapid and Stable Hematopoietic Chimerism Following Reduced Intensity Conditioning and Experimental HCT." Blood 112, no. 11 (November 16, 2008): 70. http://dx.doi.org/10.1182/blood.v112.11.70.70.
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Abstract Engraftment and the induction of tolerance to donor antigens is a central aim of allogeneic hematopoietic cell transplantation (HCT). Currently, the administration of Treg cells is being examined as a new approach to support these processes. Based upon the reported ability of IL-2 anti-IL-2 mAb complex (IACX) to expand CD4+CD25+ FoxP3+ (Tregs) in vivo, we hypothesized that the administration of this complex to allogeneic HCT recipients may expand host Treg cells and inhibit host anti-donor responses, thereby effectively facilitating hematopoietic engraftment. To begin to address these questions, the effect of IACX treatment on the frequency of circulating Tregs was examined. Two days following the second injection of IACX in normal or reduced intensity conditioned (RIC) mice, the % of circulating Tregs in IACX treated mice was strikingly increased vs. PBS treated controls. Notably, the expression of Treg CD25 (MFI) was also significantly elevated (p<0.05) in IACX treated mice, consistent with the expansion and activation of Tregs following IACX treatment. Varying regimens of the complex were then administered to RIC MHC-matched allogeneic recipients. B6 mice (RIC, 5.5 Gy TBI) transplanted with 4 × 106 BALB. B TCD-BM (day 0) were administered IACX (rIL-2/JES6-1) at days −5 and −3 (pre-HCT) or days +3 and +5 (post-HCT). In multiple independent studies, IACX treatment post-HCT consistently induced markedly superior expansion of host Treg populations at 1 wk post-HCT. Analysis of donor cells (Ly9.1+) 1 wk post-HCT clearly demonstrated that recipients treated with IACX post-HCT had markedly increased levels of circulating donor cells compared to the pre-HCT and PBS treated recipients (p<0.0001). To address the hypothesis that Treg expansion and activation following IACX treatment could inhibit host anti-donor CD8 T cell reactivity, host CD8+ T cell responses to the immunodominant donor epitope (H60) were analyzed by tetramer staining during the first 3 wks post-HCT. The frequency of these cells in recipients administered IACX post-HCT was greatly reduced compared to pre-HCT and PBS treated groups. Finally, to determine the effect of IACX treatment on engraftment, long-term chimerism was examined. Analysis for donor chimerism at 25 weeks post-HCT demonstrated: that only recipients administered IACX post-HCT were chimeric, containing high levels of donor cells vs. IACX pre-HCT and PBS controls, i.e. 36.1 ± 10.9% SE, 1.2 ± 0.785 and 0.78 ± 0.18, respectively. These findings demonstrate that infusion of IL-2 anti-IL-2mAb IACX in RIC allogeneic HCT can induce stable, long-term donor hematopoietic chimerism. Notably, the timing of IACX administration was found to be crucial with respect to conditioning and hematopoietic progenitor cell transplantation. At least part of the mechanism appears to involve the suppression of host anti-donor T cell responses, which presumably facilitates the initiation of early chimerism during the process of engraftment by donor cells. This approach may provide a new strategy to promote successful hematopoietic engraftment by manipulating endogenous Treg cells and thereby obviating the need for Treg infusions in certain transplant settings.
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Hall, Geoffrey G., Alexander G. Perry, Adam vanDijk, and Kieran M. Moore. "Influenza assessment centres: a case study of pandemic preparedness to alleviate excess emergency department volume." CJEM 15, no. 04 (July 2013): 198–205. http://dx.doi.org/10.2310/8000.2012.120808.
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ABSTRACT Objectives: Influenza assessment centres (IACs) were deployed to reduce emergency department (ED) volumes during the pH1N1 influenza outbreak in the Kingston, Frontenac, Lennox and Addington (KFL&A) public health region of Ontario, Canada, in the fall of 2009. We present a case study for the deployment of IACs to reduce ED visit volume during both periods of pandemic and seasonal communicable disease outbreak. Methods: An emergency department syndromic surveillance system was used to trigger the deployment of eight geographically distributed IACs and to time their staggered closure 3 weeks later. We compared actual and expected ED visit volumes in the KFL&A region to neighbouring regions where no IACs operated by time series regression analysis before, during, and after IAC operation. Results: The deployment of IACs was triggered with a rise in overall ED volume at the hospitals in the KFL&A region to a level 10% above the 6-month running average. The IACs assessed 2,284 patients during 3 weeks of operation. Thirtythree patients were admitted directly to the hospital from the IACs, bypassing the EDs. During the operation of the IACs, the hospitals in the KFL&A region experienced a modest decrease in daily visits when compared to the 3 previous weeks. Overall ED visit volume in the hospitals in the neighbouring regions increased 105% during the period of IAC operation. Conclusions: Operating stand-alone influenza IACs may reduce ED volumes during periods of increased demand, as observed during an anticipated pandemic situation.
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Yang, Haeun, Yoko Tabe, Kaori Saito, Rodrigo Jacamo, Helen Ma, Vivian Ruvolo, Junichi Imoto, et al. "Mitochondrial Transfer Confers Microenvironment-Mediated Resistance to Oxphos Inhibition in AML." Blood 132, Supplement 1 (November 29, 2018): 430. http://dx.doi.org/10.1182/blood-2018-99-112933.
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Abstract Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation (OxPhos) for survival and continually adapt to fluctuations in nutrient and oxygen availability in the bone marrow (BM) microenvironment. The first-in-class OxPhos inhibitor IACS-010759 (Molina, Nat. Medicine 2018) is currently in Phase 1 clinical trial in AML. To identify biomarkers of sensitivity or resistance to OxPhos inhibition, we performed Cap Analysis of Gene Expression analysis (CAGE) in primary AML samples (11 sensitive and 3 resistant to IACS-010759) and 6 AML cell lines (OCI-AML3, MOLM13, THP-1, U937, MV4;11, HL60). CAGE identified 41 gene transcripts that were significantly higher in IACS-010759 resistant primary AML samples than in sensitive samples (fold change >3.0, FDR <0.05, EdgeR). Among these, mitochondria metabolism related genes ATP1B2, GCLC, SLC25A39 and AKR1A1 showed higher baseline expression in IACS-resistant MOLM13 cells compared to sensitive OCI-AML3 cells, suggesting that the basal metabolic capacity affects sensitivity to OxPhos inhibition. Indeed, MOLM-13 showed markedly higher baseline oxygen consumption rates (OCR) and more prominent elevation of compensatory glycolytic proton efflux rate (glycoPER) after IACS-010759 treatment than OCI-AML3 cells (Seahorse XF Analyzer). The simultaneous inhibition of glycolysis by 2-deoxy-D-glucose (2-dG) and OxPhos induced synergistic cytotoxicity and proliferation inhibition (combination index, CI: 0.04, 0.81 OCI-AML3, < 0.01, 0.29 MOLM13). We next studied OxPhos inhibition under conditions mimicking BM microenvironment, by co-culturing AML cells with healthy BM-derived mesenchymal stem cells (MSC). Anti-proliferative effects of IACS-010759 were reduced by co-culture with MSC (IC50 0.01nM vs 2.1nM OCI-AML3, 65.4nM vs >10µM MOLM13). MSC co-culture increased OCR and glycoPER, and IACS-010759 decreased OCR / increased glycoPER in both cell lines. To determine the mechanism of resistance to IACS-010759 under MSC co-culture conditions, we studied the mitochondrial exchange between AML cells and MSC. We observed the bidirectional mitochondrial transfer between MSCs and AML cells. Using AML and MSC cells stably infected with mitochondria-targeted PDHA1 (GFP in AML, dsRed in MSC) to visualize the mitochondria, we found that IACS-010759 treatment facilitated transfer of AML-derived mitochondria into the adhered MSCs (24h), and MSC-derived mitochondria transferred to floating AML cells (48-72h) along with formation of tunneling nanotubes (TNTs) of AML cells, in sensitive OCI-AML3 cells (PDHA1-GFP/DsRed double positive %, control vs IACS; 9.0% vs 23.3 %). Mitochondria transfer from MSCs to AML cells was minimally observed in MOLM13 cells with elevated basal OxPhos (4.0% vs 5.0%). We next investigated IACS-010759-induced metabolic changes in AML cells interacting with bone marrow (BM) stromal cells. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) metabolite analysis further detected that IACS-010759 suppressed multiple anaplerotic amino acids in OCI-AML3 cells including glutamine and glutamic acid, which was reversed by MSC co-culture along with increase in intra-autophagosomal LC3-II in OCI-AML3 cells. These findings were not observed in MOLM13. Microenvironment-induced activation of glutamine metabolism and autophagy-associated amino acid metabolism could be additional compensatory mechanisms in response to OxPhos inhibition by IACS-010759 in BM microenvironment. Taken together, basal metabolic energetic capacity including elevated OxPhos and high compensatory glycolysis confer the AML-intrinsic resistance to IACS-010759, which can be reversed by simultaneous glycolysis inhibition. BM microenvironment facilitates secondary resistance to OxPhos inhibition through modulation of amino acid metabolism and direct mitochondrial transfer. Inhibition of these processes could enhance the anti-AML efficacy of OxPhos inhibition. Disclosures Andreeff: AstraZeneca: Research Funding. Konopleva:Stemline Therapeutics: Research Funding.
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Chevalier, Xavier, Brendan Sheehan, Craig Whittington, Mir-Masoud Pourrahmat, Lionel Duarte, Wilson Ngai, and Gustavo Constantino de Campos. "Efficacy and Safety of Hylan G-F 20 Versus Intra-Articular Corticosteroids in People with Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis." Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders 13 (January 2020): 117954412096737. http://dx.doi.org/10.1177/1179544120967370.
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Background: Direct injection of corticosteroids into the joint is a standard treatment for knee osteoarthritis (OA). However, the treatment is somewhat controversial with regard to the benefit of both single and repeated injections; evidence that they are beneficial comes from small studies that show only modest improvements. The aim of this study was to estimate the short- and long-term clinical efficacy and safety of hylan G-F 20 versus intra-articular corticosteroids (IACS) for the treatment of pain in knee OA using Bayesian network meta-analysis. Methods: Based on a pre-specified protocol, MEDLINE, Embase, and CENTRAL were searched from inception to June 2018 to identify randomized controlled trials. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials was used to assess the included studies. Hylan G-F 20 and IACS were compared using Bayesian network meta-analysis. Efficacy was evaluated at 1, 3, and 6 months, and at the final follow-up for safety outcomes. A pain hierarchy was used to select 1 pain outcome per study. Results: Forty-two trials were included for analysis. The network meta-analysis of pain showed that hylan G-F 20 may be equivalent to IACS in the short-term, but by 6 months the benefit relative to IACS was statistically significant, standardized mean difference (95% credible interval): –0.13 (–0.26, –0.01). There were no statistical differences in adverse events. Conclusions: Hylan G-F 20 may perform better in relieving pain at 6 months post-injection compared to IACS. Both agents were relatively well tolerated, with no clear differences in safety.
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Mlynek, Petr, Radek Fujdiak, Pavel Mrnustik, Bohuslav Krena, and Ludovic Apvrille. "Co-Engineering Gap Analysis of ANSI/ISA‑62443‑3‑3." International Journal of Advances in Telecommunications, Electrotechnics, Signals and Systems 9, no. 1 (April 2, 2020): 1. http://dx.doi.org/10.11601/ijates.v9i1.285.
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Nowadays, software and system development is a more complex process than ever was and it faces challenges, where security became one of the most crucial. Based upon co-engineering in the AQUAS project, complex standards covering development processes regarding safety, but performance and security are missing. In the paper, the representative standard for Industrial Automation and Control Systems (IACS) is selected for gap analysis, both as examples of issues in co-engineering in security and performance, and possibly for evolution and extension in security standards. For IACS, the ANSI/ISA 62443 defines procedures for implementing security requirements. Based upon co-engineering in the AQUAS project and experience from the real implementation of security by TrustPort practitioners of this domain, the paper introduces the 62443 standard gaps analysis with the goal to identify the missing part. Based on this analysis, the possible recommendations for extending 62443-3-3 are proposed.
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Xiang, Yang, Jianming Kang, Chunyan Zhang, Qiangji Peng, Ningning Zhang, and Xiaoyu Wang. "Analysis and Optimization Test of the Peanut Seeding Process with an Air-Suction Roller Dibbler." Agriculture 12, no. 11 (November 17, 2022): 1942. http://dx.doi.org/10.3390/agriculture12111942.
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The air-suction roller dibbler for peanuts is the core component to realizing precision seeding on film; however, the seeds in the dibbler cannot accurately fall into the seed-guiding mechanism during the work. In this study, we stabilized the seed trajectory by adjusting the installation angles of the chock block (IACB) and installation angles of the dibbler cover (IADC). We studied the seed-movement characteristics under different IACB and dibbler covers using EDEM simulation software. The separation between the seed and the baffle was obtained for different installation conditions, which were contact separation and noncontact separation. We obtained the best seeding performance when the seed was released from the edge of the dibbler cover in contact with the baffle of the seed separation tray. In the bench test, we obtained the best seed-feeding performance at 48.28° for the IACB, 12.29° for the IADC, and 3.84 km/h for the machine. The seeding pass rate was 95.35%, the missed seeding rate was 2.52%, and the reseeding rate was 2.11%. The field verification test showed that the machine worked well with the combination, and the seeding pass rate was above 92%, which meets the requirements of the single-grain precision sowing of peanuts and substantially improves the operation performance.
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Saraiva Amaral, Ana, Rosa Marina Afonso, Mário R. Simões, and Sandra Freitas. "307 - Exploratory Study on Healthcare Decision-Making Capacity Assessment." International Psychogeriatrics 32, S1 (October 2020): 65. http://dx.doi.org/10.1017/s1041610220002070.
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Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) prevalence is expected to continue to increase, due to the population ageing. MCI and AD may impact patients’ decision-making capacities, which should be assessed through the disease course. These medical conditions can affect the various areas of decision-making capacity in different ways. Decision-making capacity in healthcare is particularly relevant among this population. Elders often suffer from multimorbidity and are frequently asked to make healthcare decisions, which can vary from consenting a routine diagnostic procedure to decide receiving highly risk treatments.To assess this capacity in elders with MCI or AD, we developed the Healthcare Decision-Making Capacity Assessment Instrument (IACTD-CS - Instrumento de Avaliação da Capacidade de Tomada de Decisão em Cuidados de Saúde). This project is funded by Portuguese national funding agency for science, research and technology, FCT (SFRH/BD/139344/2018). IACTD-CS was developed based on Appelbaum and Grisso four abilities model, literature review and review of international assessment instruments. After IACTD-CS first version development, an exploratory study with focus groups was conducted. This study included focus groups with healthcare professionals and nursing homes’ professionals.The focus groups main goals were: 1) understand the participants perception regarding healthcare decision-making capacity, 2) distinguish relevant aspects of decision-making, 3) discuss the abilities and items included in IACTD-CS and 4) identify new aspects or items to be added to IACTD-CS. A content analysis of the focus groups results, with resource to MAXQDA, was conducted afterwards. This exploratory study allowed to identify professionals’ perceptions on healthcare decision-making and its results were a significant contribute to IACTD-CS development. The proposed communication aims to describe the methodology used and present the results of content analysis.
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Matre, Polina, Marina Protopopova, Ningping Feng, Jason Gay, Jennifer Greer, Juliana Velez, Hong Mu, et al. "Novel Nanomolar Potency Mitochondrial Complex I Inhibitor Iacs-1131 Selectively Kills Oxphos-Dependent AML Cells." Blood 124, no. 21 (December 6, 2014): 622. http://dx.doi.org/10.1182/blood.v124.21.622.622.
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Abstract Recent studies indicate that acute myeloid leukemia (AML) cells, including leukemia-initiating cells, are highly dependent on oxidative phosphorylation (OXPHOS) for survival, while normal hematopoietic stem cells predominantly utilize glycolysis for energy homeostasis. We have reported development of a series of novel, highly potent mitochondrial complex I inhibitors, which in vitro inhibit complex I with IC50 values <10 nM (Marszalek et al., AACR 2014 Abstract #949). These inhibitors offer excellent therapeutic potential in the OXPHOS-dependent cancer models. IACS-1131 was selected as a preclinical tool compound from the series of more than 800 compounds across distinct structural classes. Here, we report the in vitro and in vivo efficacy of IACS-1131 in AML models. Analysis of a panel of AML cell lines showed that a subset of leukemias are markedly dependent on OXPHOS for growth and survival; in this subset, IACS-1131 treatment caused steep decreases in viable cell number via induction of apoptosis. In sensitive cell lines (HL-60, OCI-AML3, KG-1, MV4;11, Kasumi-1), IACS-1131 induced pronounced apoptosis with EC50 between 10 and 100nM, consistent with the IC50 required to inhibit OXPHOS. MOLM13 and OCI-AML2 cells were less sensitive (EC50 250nM and 120nM, and a failure to induce cell death). In primary AML samples from patients with newly diagnosed or relapsed/refractory AML (n=12), the average EC50 for IACS-1131 was 14 ± 8nM in 9 samples, and exceeded 100nM in 3 samples. Consistent with the findings in AML cell lines, 10nM IACS-1131 resulted in partial responses, and 100-250nM resulted in profound loss of viability due to apoptosis induction. In contrast, this treatment caused only a moderate decrease in CD34+ cell numbers and <10% increase in apoptosis in 6 normal bone marrow samples. The effects of IACS-1131 on the two major energy-generating pathways, mitochondrial OXPHOS and glycolysis, were investigated using the Seahorse Bioscience XF96 Analyzer. Treatment for 16 hrs caused a striking dose-dependent decrease in basal oxygen consumption rates (OCR), indicating OXPHOS inhibition; reduced ATP production; and decreased maximal respiratory capacity in OCI-AML3 cells and in primary AML blasts (n=9). We confirmed inhibition of complex I in AML cells using Seahorse mitochondrial electron flow assay. These changes preceded changes in viability or apoptotic markers; as such, loss of the mitochondrial membrane potential, annexin V positivity, and induction of mitochondrial reactive oxygen species were seen only at 72 hrs of exposure. Further time-course analysis demonstrated that 2 hrs of IACS-1131 exposure caused significant inhibition of OCR in both sensitive OCI-AML3 and resistant MOLM13 cells, but in MOLM13 cells there was a greater increase in extracellular acidification rates, suggesting compensation by glycolysis. In turn, inhibition of glycolysis with 2-DG, or blockade of pyruvate dehydrogenase kinase with dicholoroacetate (which forces entry into the TCA cycle) sensitized resistant cells to IACS-1131. The intracellular metabolome (polar fraction) of OCI-AML3 cells was characterized following 2, 4, 12 and 24 hrs of treatment with 100nm IACS-1131 using high-resolution magnetic resonance spectroscopy and high mass accuracy Orbitrap mass spectrometry. IACS-1131 modulated levels of the TCA intermediates, producing increased accumulation of citrate and fumarate and decreased succinate and malate, and increased glutathione, possibly because of the oxidative stress. Furthermore, the metabolic analysis indicated a strong effect on amino acid metabolism, whereby IACS-1131 reduced (between 25% and 62% of control) multiple anaplerotic amino acids (including arginine, leucine, isoleucine, valine, phenylalanine, asparagine, histidine, and glutamine, but not aspartate). Finally, IACS-1131 at 60 mg/kg QD po demonstrated robust anti-leukemia activity in an orthotopic OCI-AML3 model. At this dose, IACS-1131 was well tolerated for >50 days and increased median survival duration by more than 5 times (Fig. 1). Studies exploring the anti-AML efficacy of single-agent IACS-1131 in primary AML xenografts are ongoing. Taken together, these data strongly indicate that OXPHOS inhibition constitutes a novel therapeutic approach that targets a unique metabolic vulnerability of AML cells and indicate that further preclinical evaluation of OXPHOS inhibitors is warranted. Figure 1 Figure 1. Figure 1 Treatment with IACS-1131 prolongs survival in a OCI-AML3 xenograft model. Luciferase-expressing OCI-AML3 cells were injected in the tail vein of NSG mice. On day 16 after injection, engraftment was confirmed and mice were randomized on the basis of IVIS-based imaging of luciferase activity after luciferin injection. For the next 58 days, mice received either vehicle or 60 mg/kg/day of IACS-1131 via oral gavage. Mice were sacrificed when body weight was reduced by >20% or for signs of morbidity. Right, bioluminescence imaging before (D0) and 10 days after 1 st dose; left survival. Figure 1. Treatment with IACS-1131 prolongs survival in a OCI-AML3 xenograft model. Luciferase-expressing OCI-AML3 cells were injected in the tail vein of NSG mice. On day 16 after injection, engraftment was confirmed and mice were randomized on the basis of IVIS-based imaging of luciferase activity after luciferin injection. For the next 58 days, mice received either vehicle or 60 mg/kg/day of IACS-1131 via oral gavage. Mice were sacrificed when body weight was reduced by >20% or for signs of morbidity. Right, bioluminescence imaging before (D0) and 10 days after 1 st dose; left survival. Disclosures No relevant conflicts of interest to declare.
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Pfrang, Steffen, Anne Borcherding, David Meier, and Jürgen Beyerer. "Automated security testing for web applications on industrial automation and control systems." at - Automatisierungstechnik 67, no. 5 (May 27, 2019): 383–401. http://dx.doi.org/10.1515/auto-2019-0021.
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Abstract Industrial automation and control systems (IACS) play a key role in modern production facilities. On the one hand, they provide real-time functionality to the connected field devices. On the other hand, they get more and more connected to local networks and the internet in order to facilitate use cases promoted by “Industrie 4.0”. A lot of IACS are equipped with web servers that provide web applications for configuration and management purposes. If an attacker gains access to such a web application operated on an IACS, he can exploit vulnerabilities and possibly interrupt the critical automation process. Cyber security research for web applications is well-known in the office IT. There exist a lot of best practices and tools for testing web applications for different kinds of vulnerabilities. Security testing targets at discovering those vulnerabilities before they can get exploited. In order to enable IACS manufacturers and integrators to perform security tests for their devices, ISuTest was developed, a modular security testing framework for IACS. This paper provides a classification of known types of web application vulnerabilities. Therefore, it makes use of the worst direct impact of a vulnerability. Based on this analysis, a subset of open-source vulnerability scanners to detect such vulnerabilities is selected to be integrated into ISuTest. Subsequently, the integration is evaluated. This evaluation is twofold: At first, willful vulnerable web applications are used. In a second step, seven real IACS, like a programmable logic controller, industrial switches and cloud gateways, are used. Both evaluation steps start with the manual examination of the web applications for vulnerabilities. They conclude with an automated test of the web applications using the vulnerability scanners automated by ISuTest. The results show that the vulnerability scanners detected 53 % of the existing vulnerabilities. In a former study using commercial vulnerability scanners, 54 % of the security flaws could be found. While performing the analysis, 45 new vulnerabilities were detected. Some of them did not only break the web server but crashed the whole IACS, stopping the critical automation process. This shows that security testing is crucial in the industrial domain and needs to cover all services provided by the devices.
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Diwasasri, Anindya, Sumadiono Sumadiono, and Sri Mulatsih. "Outcome predictors in patients with juvenile idiopathic arthritis receiving intraarticular corticosteroid therapy." Paediatrica Indonesiana 59, no. 5 (September 24, 2019): 237–43. http://dx.doi.org/10.14238/pi59.5.2019.237-43.
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Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. It can continue into adulthood and cause severe joint damage, resulting in disability and decreased quality of life.
Objective To determine the predictors of clinical outcomes in JIA patients receiving intra-articular corticosteroid injections (IACS).
Methods We conducted a retrospective cohort study of children with JIA receiving IACS therapy in Dr. Sardjito General Hospital from 1 January 2012 to 31 December 2017 by reviewing data from medical records. The dependent variables were disabilities and early remission time. Independent variables included age at diagnosis, JIA subtype, duration of disease at first diagnosis, timing of IACS, exposure to oral systemic therapy, as well as anti-nuclear antibodies (ANA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) test results. External variables were gender and nutritional status.
Results Of 36 patients who received intraarticular corticosteroid injections, 28 (77.8%) experienced remission, and 16 (50%) experienced disabilities. Female subjects (OR 5.296; 95%CI 1.143 to 24.548; P=0.027) and subjects with ESR >26 mm/h (OR 2; 95%CI 1.259 to 3.170; P=0.043) were more likely to have disabilities. Use of oral corticosteroids for ≤3 months and IACS treatment ≤ 3 months after diagnosis were predictors of early remission time (OR 6.897; 95%CI 1.869 to 25 and OR 3.290; 95%CI 1.195 to 9.091, respectively). However, only oral corticosteroid had a significant correlation in multivariate analysis.
Conclusion Female gender and ESR > 26 mm/h predict disabilities in JIA patients receiving IACS. Duration of oral corticosteroid ≤3 months and early IACS within 3 months of diagnosis correlate to earlier remission time. Shorter duration of oral corticosteroid is the only significant predictor for earlier remission time in JIA patients receiving IACS therapy.
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Terzić, Tomislav, Daniel Kerszberg, and Jelena Strišković. "Probing Quantum Gravity with Imaging Atmospheric Cherenkov Telescopes." Universe 7, no. 9 (September 14, 2021): 345. http://dx.doi.org/10.3390/universe7090345.
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High energy photons from astrophysical sources are unique probes for some predictions of candidate theories of Quantum Gravity (QG). In particular, Imaging atmospheric Cherenkov telescope (IACTs) are instruments optimised for astronomical observations in the energy range spanning from a few tens of GeV to ∼100 TeV, which makes them excellent instruments to search for effects of QG. In this article, we will review QG effects which can be tested with IACTs, most notably the Lorentz invariance violation (LIV) and its consequences. It is often represented and modelled with photon dispersion relation modified by introducing energy-dependent terms. We will describe the analysis methods employed in the different studies, allowing for careful discussion and comparison of the results obtained with IACTs for more than two decades. Loosely following historical development of the field, we will observe how the analysis methods were refined and improved over time, and analyse why some studies were more sensitive than others. Finally, we will discuss the future of the field, presenting ideas for improving the analysis sensitivity and directions in which the research could develop.
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Yang, Haeun, Yoko Tabe, Kaori Saito, Kotoko Yamatani, Rodrigo Jacamo, Helen Ma, Vivian Ruvolo, et al. "Oxphos Inhibition Induces Formation of Tunneling Nanotubes in AML Cells and Facilitates Mitochondrial Transfer from BM Stroma to AML That Contributes to Microenvironment-Mediated Drug-Resistance of AML." Blood 134, Supplement_1 (November 13, 2019): 911. http://dx.doi.org/10.1182/blood-2019-125007.
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Acute myeloid leukemia (AML) cells highly depend on oxidative phosphorylation (OxPhos) to satisfy their heightened demands for energy, and the complex I OxPhos inhibitor IACS-010759 (Molina, Nat. Med. 2018) is currently in Phase 1 clinical trial in AML. In this study, we investigated how the bone marrow (BM) microenvironment affects the response to OxPhos inhibition in AML. To characterize the molecular mechanisms of sensitivity to OxPhos inhibition, we performed Cap Analysis of Gene Expression analysis (CAGE) on 31 genetically diverse primary AML samples (20 were defined as sensitive and 11 as resistant to IACS-010759; cut off >3.0 fold annexin V(+) by 100 nM IACS-010759/DMSO at 72 hours). CAGE identified higher expression of transcription start sites (TSS) for 17 genes in IACS-010759 resistant AML samples compared to sensitive (fold change >2.0, FDR < 0.05, EdgeR), which were related to cell adhesion, integrin and/or Rho GTPase family genes that modulate intracellular actin dynamics. We next investigated the interactions between IACS-010759 sensitive OCI-AML3 cells and BM-derived mesenchymal stem cells (MSC). Under conditions mimicking the BM microenvironment, IACS-010759 upregulated the pathways of focal adhesion and ECM-receptor interaction in OCI-AML3 cells (KEGG analysis based on CAGE). In turn, MSC co-culture increased oxygen consumption by AML, induced generation of mitochondrial ROS (control 4.4% vs IACS 44.4%), increased mtDNA (2-fold by q-PCR) and upregulation of mitochondrial proteins VDAC and cytochrome C, translating into dampened growth-inhibitory effects of IACS-010759. We further demonstrated that OCI-AML3 cells adhering to MSCs were fully protected from IACS-010759 induced apoptosis (IACS-induced specific apoptosis: non-adherent cells 16.2% ± 1.6% vs adherent cells 1.6% ± 0.7%, p=0.008, 30nM, 72hours). Similarly, adherent cells were fully protected from apoptosis induced by combination of IACS and AraC. These findings indicate that direct interactions with MSC trigger compensatory activation of mitochondrial respiration, increase in mitochondrial mass and resistance to OxPhos inhibition in AML. We next hypothesized that the trafficking of mitochondria from BM stroma cells to AML cells could represent a putative mechanism of an acquired resistance to OxPhos inhibition. To visualize mitochondria, OCI-AML3 and MSC were stably transfected with mitochondria-targeted PDHA1-GFP and -dsRed, respectively. We discovered that IACS-010759 induced transfer of MSC-derived mitochondria to OCI-AML3 cells (% of GFP/dsRed double-positive OCI-AML, control 4.1 ± 1.7 vs IACS 26.2 ± 13.4, p=0.002) via tunneling nanotubes (TNTs) detected by confocal and electron microscopy (Fig.1). Mitochondria transfer was only observed in the direct contact but not in the transwell co-cultures, and was abrogated by ICAM-1 neutralizing antibody and TNT blockade with Cytochalasin B. Likewise, combination of IACS with AraC increased mitochondrial transfer. We further found that IACS-010759 induced autophagy in OCI-AML3 cells co-cultured with MSC, as noted by increased conversion of LC3-I to LC3-II, which was further enhanced by the lysosome inhibitor Bafilomycin. Additionally, we observed autophagosome formation enwrapping MSC-derived mitochondria (Fig.1F), along with the degradation of an outer mitochondrial membrane protein Tom20. Finally, IACS-010759-induced transfer of mtDNA in BM-resident AML cells was confirmed in vivo in humanized AML PDX models (n=2). Daily oral treatment of mice harboring human AML with IACS-010759 (5.0 mg/kg/day, 21 days) increased the ratio of murine/human mtDNA in human AML cells isolated from BM, in 5 days on/2 days off PDX models tested (2.1 ± 0.3 fold, n=2). In conclusion, the findings of this study indicate an important role of mitochondria trafficking from BM stromal cells to AML cells in a compensatory adaptation to OxPhos inhibition in BM microenvironment. We propose that blocking of mitochondrial transfer could enhance the anti-AML efficacy of OxPhos targeting agents. Disclosures Zhang: The University of Texas M.D.Anderson Cancer Center: Employment. Kuruvilla:The University of Texas M.D.Anderson Cancer Center: Employment. Andreeff:BiolineRx: Membership on an entity's Board of Directors or advisory committees; Breast Cancer Research Foundation: Research Funding; Oncolyze: Equity Ownership; Oncoceutics: Equity Ownership; Senti Bio: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Eutropics: Equity Ownership; Reata: Equity Ownership; Aptose: Equity Ownership; 6 Dimensions Capital: Consultancy; Daiichi Sankyo, Inc.: Consultancy, Patents & Royalties: Patents licensed, royalty bearing, Research Funding; Jazz Pharmaceuticals: Consultancy; Celgene: Consultancy; Amgen: Consultancy; AstaZeneca: Consultancy; CPRIT: Research Funding; NIH/NCI: Research Funding; Center for Drug Research & Development: Membership on an entity's Board of Directors or advisory committees; Cancer UK: Membership on an entity's Board of Directors or advisory committees; NCI-CTEP: Membership on an entity's Board of Directors or advisory committees; German Research Council: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; NCI-RDCRN (Rare Disease Cliln Network): Membership on an entity's Board of Directors or advisory committees; CLL Foundation: Membership on an entity's Board of Directors or advisory committees. Konopleva:Astra Zeneca: Research Funding; Agios: Research Funding; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Forty-Seven: Consultancy, Honoraria; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding.
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Frisch, Harold P., and Robert G. Vos. "The integrated analysis capability (IAC level 2.0)." Engineering with Computers 4, no. 1-2 (March 1988): 53–63. http://dx.doi.org/10.1007/bf01201472.
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Gismondi, Roberto, Loredana De Gaetano, and Massimo Russo. "Estimation of olive oil production based on the use of administrative data." Management Theory and Studies for Rural Business and Infrastructure Development 36, no. 4 (November 3, 2014): 835–43. http://dx.doi.org/10.15544/mts.2014.078.
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Italy is one of the most relevant countries in the European Union as regards crops and, in particular, olive oil production. Actually, statistical data on olive oil are provided by the 20 Italian Regions to ISTAT through estimates supplied by experts and / or local panels of influent farmers and category associations. However, more precise estimates may be derived from the administrative data collected by AGEA, which is the Italian acronym for Integrated Administration and Control System (IACS). IACS is in charge of receiving from farmers declarations of production, on the basis of which they receive subsidies. The main goals of the work are the following ones: 1) to transform the administrative IACS database into a statistical one; 2) to compare different methodologies for producing monthly estimates of olive oil productions in presence of missing declarations; 3) to aggregate the IACS yearly olive oil production, comparing these estimates with those supplied by experts estimates. The paper analyses the main outcomes concerning the Region Apulia (South Italy), where the 40.1% of Italian olive oil is produced.
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Liu, Linfan, Huajun Zhang, Jupeng Xie, and Qin Zhao. "Dynamic Evacuation Planning on Cruise Ships Based on an Improved Ant Colony System (IACS)." Journal of Marine Science and Engineering 9, no. 2 (February 19, 2021): 220. http://dx.doi.org/10.3390/jmse9020220.
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The emergency evacuation route planning of cruise ships directly affects the safety of all crew members and passengers during emergencies. Research on the planning of emergency evacuation routes for cruise ships is a frontier subject of maritime safety. This study proposes an improved ant colony system (IACS) to solve the evacuation route planning of crowds on cruise ships. The IACS, which is different from common single-path ant colony system (ACS) evacuation algorithms, is used to solve the multipath planning problem of crowd evacuation from cruise ships by considering crowd density and speed in the model. An increasing flow method is introduced into the IACS to improve the efficiency of the proposed algorithm. Numerical experiments show that this method meets the requirements of evacuation analysis guidelines for new and existing passenger ships (MSC.1/Circ.1533)and can effectively and efficiently plan the emergency evacuation path for cruise ship crowd.
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Murphy, Sean, and Rachel Player. "Discretisation and Product Distributions in Ring-LWE." Journal of Mathematical Cryptology 15, no. 1 (November 17, 2020): 45–59. http://dx.doi.org/10.1515/jmc-2020-0073.
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AbstractA statistical framework applicable to Ring-LWE was outlined by Murphy and Player (IACR eprint 2019/452). Its applicability was demonstrated with an analysis of the decryption failure probability for degree-1 and degree-2 ciphertexts in the homomorphic encryption scheme of Lyubashevsky, Peikert and Regev (IACR eprint 2013/293). In this paper, we clarify and extend results presented by Murphy and Player. Firstly, we make precise the approximation of the discretisation of a Normal random variable as a Normal random variable, as used in the encryption process of Lyubashevsky, Peikert and Regev. Secondly, we show how to extend the analysis given by Murphy and Player to degree-k ciphertexts, by precisely characterising the distribution of the noise in these ciphertexts.
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Wang, Longting, Liping Sun, Hai Sun, Xiangkun Meng, and Jichuan Kang. "Risk Propagation Evolution Analysis of Oil and Gas Leakage in FPSO Oil and Gas Processing System by Mapping Bow-Tie into Directed Weighted Complex Network." Water 14, no. 18 (September 13, 2022): 2857. http://dx.doi.org/10.3390/w14182857.
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An innovative methodology is proposed to identify potential risk factors and possible accident escalation consequences, and to determine the evolution of an accident from cause to consequence, thereby to identify the most probable path and discover key risk factors along the path rapidly. Based on the principle of a directed weighted complex network (DWCN), the bow-tie (BT) model, risk entropy and the improved ant colony optimization (IACO) algorithm are integrated into this methodology. First, the qualitative analysis of risk evolution based on the BT model is carried out. The evolution development based on accident suppression can be divided into two stages: accident precursor stage and accident evolution stage. Then, a new method for mapping BT into DWCN is proposed. Lastly, the shortest path analysis of risk evolution based on the IACO algorithm is carried out, fuzzy set theory (FST) is introduced to calculate the failure probability of risk factors, and risk entropy is used to represent the uncertainty of risk propagation. Thus, the IACO algorithm can be used to calculate the shortest path of risk evolution. The proposed method is applied to oil and gas leakages in the FPSO oil and gas processing system. The results show that it is an effective method to identify the shortest evolution path and the most vulnerable risk factors.
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H., Makaryus, EI-Mandy A., and El gamel A. "ANALYSIS OF JAMMING TECHNIQUE AGAINST IAC MONOPULSE RADAR." International Conference on Aerospace Sciences and Aviation Technology 9, ASAT Conference, 8-10 May 2001 (May 1, 2001): 1–11. http://dx.doi.org/10.21608/asat.2001.31166.
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H., Makaryus, EI-Mandy A., and El gamel A. "ANALYSIS OF JAMMING TECHNIQUE AGAINST IAC MONOPULSE RADAR." International Conference on Aerospace Sciences and Aviation Technology 9, no. 9 (May 1, 2001): 1139–49. http://dx.doi.org/10.21608/asat.2001.59812.
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Liu, Yang, Taylor Bell, Hui Zhang, Yuting Sun, Carrie J. Li, Ningping Feng, Shengjian Huang, et al. "Targeting Oxphos Pathway Against Ibrutinib Resistance to Mantle Cell Lymphoma." Blood 128, no. 22 (December 2, 2016): 290. http://dx.doi.org/10.1182/blood.v128.22.290.290.
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Abstract Background: Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy that is initially responsive but ultimately relapses to frontline therapy. Ibrutinib, a first-in-class, once-daily, oral covalent inhibitor of Bruton's tyrosine kinase (BTK) has achieved 68% of overall response rate in relapsed/refractory mantle cell lymphoma (MCL) patients. However, the vast majority of MCL patients experience disease progression, demonstrating that standard-of-care approaches are failing and that a means for targeting ibrutinib resistant MCL is clinically needed. Our hypothesis is that the ibrutinib-resistant MCL may rely on the mitochondrial oxidative phosphorylation (OXPHOS) pathway to produce energy for tumor growth. In this study, we investigated the effects of IACS-010759, a small molecule mitochondrial complex I inhibitor discovered in MD Anderson Cancer Center which can block the OXPHOS pathway, to overcome ibrutinib resistance in MCL in vitro and in a patient-derived xenograft (PDX) model. Methods: The OXPHOS metabolic pathways were investigated by RNASeq in a panel of ibrutinib-sensitive and -resistant MCL samples. Cell growth inhibition assays were tested after 72-hour treatment with IACS-010759 in ibrutinib-resistant MCL cell lines, Z-138 and Maver-1, and ibrutinib-sensitive MCL cell lines, Rec-1, Mino, and Jeko-1, by CellTiter-Glo luminescent cell viability assay (Promega). Furthermore, an IBN-resistant MCL PDX model was established and the therapeutic effects and tolerability of IACS-010759 were investigated in the primary MCL-bearing PDX model. Results: We have done RNA sequencing (RNASeq) in 7 primary ibrutinib-resistant and 16 ibrutinib-sensitive MCL patient samples, and analyzed the data using Gene Set Enrichment Analysis (GSEA) software. The results demonstrated that the OXPHOS pathway was activated in the primary ibrutinib-resistant MCL cells but not ibrutinib-sensitive MCL cells. Based on the RNASeq data, we selected an OXPHOS inhibitor IACS-010759 to investigate its effects on both primary ibrutinib-resistant and ibrutinib-sensitive MCL cells in vitroand in PDX mice. IACS-010759 significantly inhibited cell proliferation in ibrutinib-resistant MCL cell lines, Z-138 and Maver-1, but not in ibrutinib-sensitive MCL cell lines, Rec-1, Mino, and Jeko-1, during a 72-hour incubation. Furthermore, the primary ibrutinib-resistant MCL PDX mice were administrated with 10 mg/kg IACS-10759 by oral gavage, for 28 days using a 5 on/2 off dosing schedule. Our data showed that IACS-010759 completely eradicated tumor growth in ibrutinib-resistant MCL PDX mice (n=5, p=0.045). All mice tolerated the treatment dose and no toxicity was found during 28 days of IACS-010759 treatment. Conclusions: The OXPHOS inhibitor IACS-010759 overcomes ibrutinib resistance both in vitro and in the PDX mouse model. The investigation of its mechanism-of-action is ongoing. IACS-010759 could have the potential for clinical use in ibrutinib-resistant relapsed/refractory MCL patients. Disclosures Wang: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana BioSciences: Research Funding; Kite Pharma: Research Funding; Juno Therapeutics: Research Funding; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding; Dava Oncology: Honoraria; BeiGene: Research Funding; Acerta: Consultancy, Research Funding.
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Zhang, Long, Jian Xing Yu, Wei Lin Ma, and Bao Jian Wang. "Comparative Safety Analysis of Different Bollard Supporting Structures." Applied Mechanics and Materials 325-326 (June 2013): 1297–300. http://dx.doi.org/10.4028/www.scientific.net/amm.325-326.1297.
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Detailed finite element analysis has been carried out for different bollard supporting structures by ANSYS software. From the analysis results, it can be seen that the bollard supporting structures are of adequate strength to take the design load transferred from the mooring rope during operation considering the requirement on strength criteria from IACS, and strength check is performed in accordance with the updated relevant ABS standard. Finally, a comparison of these different bollard supporting structures is made to find out their own advantages from safety and other aspects.
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Anoop, Shajith, Jesse Krakauer, Nir Krakauer, and Anoop Misra. "A Body shape index significantly predicts MRI-defined abdominal adipose tissue depots in non-obese Asian Indians with type 2 diabetes mellitus." BMJ Open Diabetes Research & Care 8, no. 1 (October 2020): e001324. http://dx.doi.org/10.1136/bmjdrc-2020-001324.
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IntroductionWe aimed to determine the correlations of volumes of subcutaneous abdominal adipose tissue (SCAT) (anterior, posterior, superficial and deep), total SCAT, intraperitoneal adipose tissue, retroperitoneal abdominal adipose tissue (RPAT), total intra-abdominal adipose tissue (IAAT), pancreatic volume, liver span, total body fat (TBF) and truncal fat mass (TFM) with anthropometric indices, viz., A Body Shape Index (ABSI), Hip Index, their Z scores and Anthropometric Risk Index in non-obese (body mass index (BMI) <25 kg/m2) Asian Indians with type 2 diabetes mellitus (T2DM).Research design and methodsNon-obese patients with T2DM (cases; n, 85) and BMI-matched, healthy subjects (controls; n, 38) underwent anthropometry, dual energy X ray absorptiometry (DXA) for estimation of TBF, TFM and 1.5 T MRI for estimation of volumes of abdominal adipose tissue depots, pancreas and liver span. Spearman’s correlation analysis and Receiver Operator Characteristic curve analysis were applied.ResultsThe Z score of ABSI (Z_ABSI) showed significantly positive correlation with volumes of all depots of abdominal SCAT, total IAAT and RPAT in cases. Area under the curve for Z_ABSI (0.87) showed higher sensitivity: 82.0 %, specificity: 81.5 %, at a predictive cut-off value of 0.49 for abdominal adiposity.ConclusionIn non-obese Asian Indians with T2DM, the Z_ABSI showed significant correlation with IAAT and SCAT and higher predictive accuracy for abdominal adiposity.Highlights of the studyThis is the first MRI-based study in the context of ABSI in non-obese (BMI <25 kg/m2) Asian Indians with T2DM. Findings indicate that Z_ABSI has high predictive accuracy for abdominal adiposity in non-obese Asian Indians. The Z_ABSI index showed significantly positive correlation with volumes of adipose tissue depots, viz., abdominal SCAT, total IAAT and RPAT in cases.
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Zhang, Qi, Alessia Lodi, Shannon Renee Sweeney, Lina Han, Tianyu Cai, Vinitha Mary Kuruvilla, Antonio Cavazos, et al. "Inhibiting Mitochondria Function By Bcl-2 Inhibitor Venetoclax and Complex I Inhibitor Iacs-010759 Eliminate Leukemia Cells in Pre-Clinical AML Models." Blood 134, Supplement_1 (November 13, 2019): 3927. http://dx.doi.org/10.1182/blood-2019-124494.
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Previous studies have demonstrated that AML is BCL-2 dependent malignancy, and leukemia stem cell (LSC) rely on BCL-2 for survival (Pan, Cancer Discovery 2014;Lagadinou, Cell Stem Cell, 2013). Selective Bcl-2 inhibitor venetoclax (ABT-199) combined with azacitidine was reported to inhibit complex II of the mitochondrial transport chain in AML (Pollyea, Nat Med 2018). IACS-010759, a novel complex I inhibitor, demonstrated effective inhibition of cell respiration and potent anti-leukemia effect in AML pre-clinical models (Molina, Nat Med 2018). We designed the experiments to study the combined efficacy and mechanisms of action of venetoclax and IACS-010759 in AML. In vitro, priming of MOLM-13 cells with 20nM venetoclax for 24hrs followed by 10nM IACS-010759 for 1hr triggered 60% reduction in oxygen consumption rate (OCR), while only partial inhibition (<15% OCR reduction) was seen in cells treated with these agents separately. This translated in accelerated loss of the mitochondrial membrane potential by JC-1 flow cytometry, cleavage of caspase 3 and potent (>70%) reduction of viable cell numbers (OCI-AML2, MV-4-11, and MOLM-13). We have further shown by co-immunoprecipitation studies that venetoclax disrupts interaction of BCL-2 with the mitochondrial protein VDAC known to regulate ADP/ATP exchange during electron transport across mitochondria membrane. In addition, an MS-based metabolomics analysis indicated that ATP and CTP intracellular levels dropped to undetectable levels following treatment with ABT-199 (with or without IACS). ADP, GDP and UDP levels were unchanged with ABT-199; however, GDP levels dropped to undetectable levels following the combined treatment. Moreover, ABT-199 significantly increased intracellular levels of AMP, UMP, CMP and GMP and this accumulation of mono-nucleotides was enhanced by the combination of ABT-199 and IACS-010759. In primary AML samples (n=3) and PDX cells (n=4) cultured ex vivo, combined venetoclax and IACS-010759 at low nanomolar doses reduced viable cell numbers in an additive or synergistic fashion. To better understand the role of BCL-2 in cellular respiration, we examined the oxygen consumption rates (OCR) in control or Bcl-2-overexpressing HL-60 cells (a kind gift of Dr. K. Bhalla, MDACC). The HL-60/BCL-2 cells had higher basal and maximal OCR than the control cells by Seahorse analysis, and higher mitochondrial ROS production by H2DCFDA and MitoSOX Red flow cytometry. BCL-2 inhibition with 100nM venetoclax for 2 hrs induced ROS production in control HL-60 cells but not in cells with BCL-2 overexpression. Further, cells with BCL-2 overexpression were less sensitive to IACS-010759. These data suggest that BCL-2 facilitates cellular respiration and reduces efficacy of the mitochondrial inhibitors. Given recent accelerated FDA approval of venetoclax and azacitidine combination for elderly unfit AML, we next tested the efficacy of the "triple" combination of venetoclax, azacitidine and IACS-010759 in the in vivoAML PDX model. We injected AML PDX cells 3747422 harboring IDH1, NMP1, NRAS, CEBPA, FLT3-ITD mutations into NRG mice and upon engraftment, randomized mice into 4 groups to receive vehicle, venetoclax (50mg/kg, 5 days on/2 days off, day 1-21) with azacitidine (1.25mg/kg daily , day 1-7), IACS-010759 (1mg/kg, 5 days on/2 days off, day 1-14), or the triple combination. Therapy was well tolerated, without any apparent weight loss or toxicities. All therapies reduced circulating leukemia burden with the best efficacy seen in the triple-therapy cohort, with average circulating tumor burden of 31.2%, 6.9%, 5.1% and 0.4% in vehicle, IACS-010759, venetoclax/azacitidine and triple-therapy cohorts, respectively. Survival analysis and additional PDX models are ongoing and will be reported. In summary, these findings indicate that BCL-2 modulates mitochondrial respiration in addition to its established anti-apoptotic role. Venetoclax disrupts the BCL-2/VDAC interactions and reduces mitochondrial respiration, which is facilitated by the combined therapy with mitochondrial complex I inhibitor IACS-010759. Our preliminary findings indicate potent anti-AML activity of the dual and triple (with hypomethylating agent) combinations in vitroand in vivo. Disclosures Zhang: The University of Texas M.D.Anderson Cancer Center: Employment. Kuruvilla:The University of Texas M.D.Anderson Cancer Center: Employment. Konopleva:Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; Calithera: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding; Agios: Research Funding.
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Sari, Rida Perwita, Sri Hastuti, and Oryza Tannar. "Female Auditor and Audit Quality Based on Internal Audit Capability Model (IACM) in the Public Sector." Journal of Economics, Business, and Government Challenges 3, no. 2 (April 18, 2021): 95–106. http://dx.doi.org/10.33005/ebgc.v3i2.122.
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The purpose of this study is to examine the influence of competence, Independence and Pressure of Obedience to Audit Quality based on Internal Audit Capability Model (IACM). This research contributes the theoretical and practical benefits as the form of adoption of agency theory and attribution theory and suggestions to improve the expertise of female auditors by taking into account the competence, independence, and pressure of obedience to produce quality inspection in the field of supervision.
This study uses a quantitative approach. The analysis technique used in this research is Partial Least Square (PLS) with the help of warpPLS software. The subject of this study is the Inspectorate of East Java Province with a sample of female auditors in the Inspectorate of East Java Province which amounted to 30 female auditors. The results of this study indicate that competence affects the Audit Quality based on Internal Audit Capability Model (IACM), while the independence and pressure of obedience do not effect the Audit Quality based on Internal Audit Capability Model (IACM).
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Sari, Rida Perwita, Sri Hastuti, and Oryza Tannar. "Audit Quality Based on Internal Audit Capability Model (IACM) and Gender as Mediating Variabel in the Public Sector." Journal of Economics, Business, and Government Challenges 2, no. 1 (June 19, 2019): 22–38. http://dx.doi.org/10.33005/ebgc.v2i1.61.
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The purpose of this study is to examine the influence of competence, Independence, Pressure of Obedience and internal control system to Audit Quality based on Internal Audit Capability Model (IACM) and gender as mediating variable. This research contributes the theoretical and practical benefits as the form of adoption of agency theory and attribution theory and suggestions to improve the expertise of auditors by taking into account the competence, independence, and pressure of obedience and internal control system to produce quality inspection in the field of supervision. This study uses a quantitative approach. The analysis technique used in this research is Partial Least Square (PLS) with the help of warpPLS software. The subject of this study is the Inspectorate of East Java Province with a sample of auditors in the Inspectorate of East Java Province which amounted to 53 auditors. The results of this study indicate that competence and internal control system affects the Audit Quality based on Internal Audit Capability Model (IACM), while the independence, pressure of obedience and gender do not affect the Audit Quality based on Internal Audit Capability Model (IACM).
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Teixeira, Angelo P., C. Guedes Soares, Nian-Zhong Chen, and Ge Wang. "Uncertainty Analysis of Load Combination Factors for Global Longitudinal Bending Moments of Double-hull Tankers." Journal of Ship Research 57, no. 01 (March 1, 2013): 42–58. http://dx.doi.org/10.5957/jsr.2013.57.1.42.
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The present article aims at assessing the probabilistic characteristics of the load combination factors for global longitudinal bending moments of double-hull tankers. The calculations are performed based on a sample of oil tankers representative of the range of application of the Association of Classification Societies' (IACS)–Common Structural Rules (CSR) design rules. The article starts by reviewing the probabilistic models that have been proposed to model stillwater and wave-induced loads and their characteristic extreme values. Different load combination methods are also reviewed including an analytical method that provides the combined characteristic value of stillwater and wave-induced bending moments based on the Poisson assumption for upcrossing events and using the first-order reliability method in combination with the point-crossing method. The predictions of the different load combination methods are assessed on the basis of a sample of five oil tankers adopted during the IACS-CSR design rules development process. A parametric and an uncertainty propagation study are then performed to identify the range of variation and the probabilistic models of the load combination factors that are applicable to double-hull tankers.
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Huang, Chi-Yo, Min-Jen Yang, Jeen-Fong Li, and Hueiling Chen. "A DANP-Based NDEA-MOP Approach to Evaluating the Patent Commercialization Performance of Industry–Academic Collaborations." Mathematics 9, no. 18 (September 16, 2021): 2280. http://dx.doi.org/10.3390/math9182280.
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The industry–academic collaboration (IAC) in developed and developing countries enables these economies to gain momentum in continuous innovation and, thus, economic growth. Patent commercialization is one major channel of knowledge flow in IAC. However, very few studies consider the flow of knowledge between industrial firms and universities. Moreover, ways that the patent commercialization performance of IACs can be evaluated are rarely discussed. Therefore, defining an analytic framework to evaluate the performance of IAC from the aspect of patent commercialization is critical. Traditionally, data envelopment analysis (DEA) models have widely been adopted in performance evaluation. However, traditional DEA models cannot accurately evaluate the performance of IACs with complex university–industry interconnections, the internal linkages, or linking activities of knowledge-flow within the decision-making units (DMUs), i.e., the IACs. In order to solve the abovementioned problems, this study defines a multiple objective programming (MOP)-based network DEA (NDEA), with weighting derived from the decision-making trial and evaluation laboratory (DEMATEL)-based analytic network process (ANP), or the DANP. The proposed analytic framework can evaluate the efficiency of decision-making units (DMUs) with a network structure (e.g., supply chains, strategic alliances, etc.) based on the weights that have been derived, based on experts’ opinions. An empirical study based on the performance of the patent commercialization of Taiwanese IACs was used to demonstrate the feasibility of the proposed framework. The results of the empirical research can serve as a basis for improving the performance of IAC.
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Paik, Jeom kee, Jin Young Kim, and Min Soo Kim. "Ultimate Limit State Performance of 170k Bulk Carrier Structures: Pre-CSR versus CSR Designs." Marine Technology and SNAME News 46, no. 03 (July 1, 2009): 174–82. http://dx.doi.org/10.5957/mtsn.2009.46.3.174.
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The objective of the present paper is to evaluate the ultimate limit state (ULS) performance of 170k bulk carrier structures designed by the IACS common structural rules (CSR) method, compared with the similar-class/type bulk carrier structure designed by the IACS pre-CSR method. The ultimate strengths of stiffened plate structures in deck, side, and bottom parts, and hull girders against vertical bending moment, are computed for the two designs, and the resulting computations are compared. ALPS/ULSAP program is used for the ultimate limit state assessment of stiffened plate structures, and ALPS/HULL program is employed for the progressive hull collapse analysis. The insights and developments obtained from the present study are documented.
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Zhang, Liang, Hui Zhang, Hui Guo, Yuting Sun, Ningping Feng, Joseph R. Marszalek, Makhdum Ahmed, Krystle Nomie, and Michael Wang. "A Novel Patient-Derived Xenograft Model of Secondary CD20- CNS Lymphoma for Mechanistic and Therapeutic Exploration." Blood 132, Supplement 1 (November 29, 2018): 1669. http://dx.doi.org/10.1182/blood-2018-99-112205.
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Abstract Introduction The majority of secondary central nervous system (CNS) lymphoma cases are derived from histologically high-grade systemic lymphomas such as diffuse-large B cell lymphoma (DLBCL) and Burkitt's lymphoma. These CNS lymphomas are associated with poor prognosis and a low likelihood of long-term survival, especially rituximab-ineffective CD20- lymphoma. To investigate the biological features and potential therapeutic targets of CNS-involved CD20- lymphoma, we established the first known patient-derived xenograft (PDX) model using cerebrospinal fluid (CSF). Methods Six- to 8-week-old male NSG mice (Jackson Laboratory) were housed and monitored in our animal research facility. All experimental procedures and protocols were approved by the Institutional Animal Care and Use Committee of The University of Texas MD Anderson Cancer Center. A total of 0.08 million cells were isolated from 2 mL of CSF obtained from a CD20- CD79A- DLBCL patient with Bcl-2 and Myc rearrangements (double-hit). The isolated cells were directly injected into a human fetal bone chip implanted into NSG (NSG-hu) mice. After passage, the mice were administered several small molecules, and tumor burden was measured via tumor volume and human β2M levels over the course of treatment. Kaplan-Meier survival analysis was also performed. PDX tissue was collected for histological analysis, immunophenotyping, genotyping, and proteomics analysis. Results The PDX tumors possessed the same histological, genetic and immunophenotypical features as the primary patient tumor cells. The PDXs had Bcl-2 and Myc rearrangements and were positive for CD10, CD19, CD22, and CD45 and were negative for CD5, CD20, and CD79A. After tumor passage, the mice were treated with vehicle, 50 mg/kg ibrutinib (Bruton's tyrosine kinase (BTK) inhibitor) oral gavage daily, 50 mg/kg ABT199 (Bcl-2 inhibitor) oral gavage daily, 1 mg/kg carfilzomib (proteasome inhibitor) i.v. twice per week, or 7.5 mg/kg IACS-010759 (oxidative phosphorylation (OXPHOS) inhibitor) oral gavage daily. As shown in Figure 1, the PDX tumor was resistant to the BTK inhibitor ibrutinib and moderately responsive to the proteasome inhibitor carfilzomib. Although the Bcl-2 gene was rearranged, the PDX model only had a partial response to the Bcl-2 inhibitor ABT-199 (ABT-199 vs control, p = 0.0004). In contrast, inhibition of the OXPHOS pathway with IACS-010759 significantly inhibited 96% tumor growth (IACS-010759 vs control, p < 0.00001) and prolonged mouse survival by approximately 25 days compared with the vehicle control and the other drugs (IACS-010759 vs control, ABT-199, or ibrutinib, p < 0.0001). Moreover, proteomics analysis demonstrated that IACS-010759 not only inhibited OXPHOS but also upregulated the pro-apoptotic protein Bim. Conclusion To our knowledge, this is the first PDX model generated from the CSF of a CD20- double-hit DLBCL patient. With this PDX model, we determined that the OXPHOS inhibitor IACS-010759 is a promising therapeutic agent for this aggressive cancer. Disclosures Wang: Acerta Pharma: Honoraria, Research Funding; Kite Pharma: Research Funding; Novartis: Research Funding; Pharmacyclics: Honoraria, Research Funding; Dava Oncology: Honoraria; Juno: Research Funding; MoreHealth: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Husain, Nursuci Putri, Nursanti Novi Arisa, Putri Nur Rahayu, Agus Zainal Arifin, and Darlis Herumurti. "LEAST SQUARES SUPPORT VECTOR MACHINES PARAMETER OPTIMIZATION BASED ON IMPROVED ANT COLONY ALGORITHM FOR HEPATITIS DIAGNOSIS." Jurnal Ilmu Komputer dan Informasi 10, no. 1 (February 28, 2017): 43. http://dx.doi.org/10.21609/jiki.v10i1.428.
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Many kinds of classification method are able to diagnose a patient who suffered Hepatitis disease. One of classification methods that can be used was Least Squares Support Vector Machines (LSSVM). There are two parameters that very influence to improve the classification accuracy on LSSVM, they are kernel parameter and regularization parameter. Determining the optimal parameters must be considered to obtain a high classification accuracy on LSSVM. This paper proposed an optimization method based on Improved Ant Colony Algorithm (IACA) in determining the optimal parameters of LSSVM for diagnosing Hepatitis disease. IACA create a storage solution to keep the whole route of the ants. The solutions that have been stored were the value of the parameter LSSVM. There are three main stages in this study. Firstly, the dimension of Hepatitis dataset will be reduced by Local Fisher Discriminant Analysis (LFDA). Secondly, search the optimal parameter LSSVM with IACA optimization using the data training, And the last, classify the data testing using optimal parameters of LSSVM. Experimental results have demonstrated that the proposed method produces high accuracy value (93.7%) for the 80-20% training-testing partition.
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Karnanda, A., and Habibi A. Naufal. "THE COMPARISON BETWEEN TWO METHODS FOR THE RELIEF OF KNEE OSTEOARTHRITIS PAIN USING OXFORD KNEE SCORE (IMPROVEMENT CHANGES AFTER 4 WEEK FOLLOW UP INJECTION) : INTRAARTICULAR AND GENICULAR NERVE BLOCK IN BLAMBANGAN GENERAL DISTRICT HOSPITAL BANYUWANGI." Orthopaedic Journal of Sports Medicine 8, no. 5_suppl5 (May 1, 2020): 2325967120S0006. http://dx.doi.org/10.1177/2325967120s00061.
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Pain is the hallmark symptom of OA. IACI can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with knee OA. Recent study reported successful pain relief by ablation of the three branches of the Genicular nerve [superior lateral (SL), superior medial (SM), and inferior medial (IM). In the ultrasound-guided GNB technique, these three nerves were selected for the same reasons. Previous studies have identified OKS thresholds to aid the clinician in presenting the expected outcome of surgery in a meaningful way to the patient (OKS provides a means of comparing preoperative and post-operative health status).This cross-sectional, respondents were filled OKS questionaire, and they were self-reported a diagnosis of OA at least one knee by a physician, reported more than 3 months of persistent OA pain. These data were collected at the first post-injection (IACI &GNB) and at 4 week followup visit. The analysis was performed by Independent T-test in SPSS version 22. In IACI group the mean of initial OKS was 37,81±6,87 compare to 34,94±6.14 in GNB group. After 4 weeks, it increased to 42±7.14 and 42,84±7,67 respectively. A total of 82 patients were randomized, with patients receiving an injection, 32 receiving IAIC injection and 50 receiving GNB injection. From Independent Samples T Test, GNB injection demonstrated significantly greater pain reductions and greater percent OKS score improvement than IACI up to 4 weeks postinjection. Comparing two methods, there were significant difference between two groups based on OKS: p=0.000
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Knödlseder, J., L. Tibaldo, D. Tiziani, A. Specovius, J. Cardenzana, M. Mayer, N. Kelley-Hoskins, et al. "Analysis of the H.E.S.S. public data release with ctools." Astronomy & Astrophysics 632 (December 2019): A102. http://dx.doi.org/10.1051/0004-6361/201936010.
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The ctools open-source software package was developed for the scientific analysis of astronomical data from Imaging Air Cherenkov Telescopes (IACTs), such as H.E.S.S., VERITAS, MAGIC, and the future Cherenkov Telescope Array (CTA). To date, the software has been mainly tested using simulated CTA data; however, upon the public release of a small set of H.E.S.S. observations of the Crab nebula, MSH 15–52, RX J1713.7–3946, and PKS 2155–304 validation using real data is now possible. We analysed the data of the H.E.S.S. public data release using ctools version 1.6 and compared our results to those published by the H.E.S.S. Collaboration for the respective sources. We developed a parametric background model that satisfactorily describes the expected background rate as a function of reconstructed energy and direction for each observation. We used that model, and tested all analysis methods that are supported by ctools, including novel unbinned and joint or stacked binned analyses of the measured event energies and reconstructed directions, and classical On-Off analysis methods that are comparable to those used by the H.E.S.S. Collaboration. For all analysis methods, we found a good agreement between the ctools results and the H.E.S.S. Collaboration publications considering that they are not always directly comparable due to differences in the datatsets and event processing software. We also performed a joint analysis of H.E.S.S. and Fermi-LAT data of the Crab nebula, illustrating the multi-wavelength capacity of ctools. The joint Crab nebula spectrum is compatible with published literature values within the systematic uncertainties. We conclude that the ctools software is mature for the analysis of data from existing IACTs, as well as from the upcoming CTA.