gebhart/patrepeval huggingface dataset:
Modeling a Two-Phase Control-Oriented Transient Model of a Single PEM Fuel Cell (2010)

This paper proposed a 1D non-isothermal control-oriented transient model of PEM fuel cell unit considering the two-phase water dynamics in gas flow channel, gas diffusion layer, catalyst layer and membrane. It is known that the accumulated liquid water in the gas flow channels can block the transport path in the gas diffusion layer for the reactant gases and degrade the performance of the fuel cell, while the proper water amount in the gas flow channels and other layers can help to maintain high proton conductivity in the membrane. The I-V curve and the change of gas concentrations, liquid water amount and temperature at specific operating conditions are obtained by sweeping the current of fuel cell. The voltage, gas concentration, temperature and water dynamic changes are investigated by applying the step change of the load current. The fuel cell performance affected by temperature and water dynamics is studied by the analysis of the simulation result.
sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae (2021)

Epoxyeicosatrienoic acids (EETs) have potent antiinflammatory properties. Hydrolysis of EETs by soluble epoxide hydrolase/ epoxide hydrolase 2 (sEH/EPHX2) to less active diols attenuates their antiinflammatory effects. Macrophage activation is critical to many inflammatory responses; however, the role of EETs and sEH in regulating macrophage function remains unknown. Lung bacterial clearance of Streptococcus pneumoniae was impaired in Ephx2-deficient (Ephx2-/-) mice and in mice treated with an sEH inhibitor. The EET receptor antagonist EEZE restored lung clearance of S. pneumoniae in Ephx2-/- mice. Ephx2-/- mice had normal lung Il1b, Il6, and Tnfa expression levels and macrophage recruitment to the lungs during S. pneumoniae infection; however, Ephx2 disruption attenuated proinflammatory cytokine induction, Tlr2 and Pgylrp1 receptor upregulation, and Ras-related C3 botulinum toxin substrates 1 and 2 (Rac1/2) and cell division control protein 42 homolog (Cdc42) activation in PGN-stimulated macrophages. Consistent with these observations, Ephx2-/- macrophages displayed reduced phagocytosis of S. pneumoniae in vivo and in vitro. Heterologous overexpression of TLR2 and peptidoglycan recognition protein 1 (PGLYRP1) in Ephx2-/- macrophages restored macrophage activation and phagocytosis. Human macrophage function was similarly regulated by EETs. Together, these results demonstrate that EETs reduced macrophage activation and phagocytosis of S. pneumoniae through the downregulation of TLR2 and PGLYRP1 expression. Defining the role of EETs and sEH in macrophage function may lead to the development of new therapeutic approaches for bacterial diseases.
Abstract 2097: Targeting aneuploidy with NMS-P153, a tight binder inhibitor of the spindle assembly checkpoint MPS1 (TTK) kinase. (2013)

Abstract Aneuploidy is one of the major hallmarks of cancer and is a unique property of tumoral cells. Targeting of the molecular mechanisms required for growth of aneuploid cells is a potential strategy for developing new therapies with preferential activity against cancer. The Spindle Assembly Checkpoint (SAC) is a mitotic mechanism required for proper chromosomal segregation, ensuring that cells do not divide until all sister chromatids correctly align to the metaphase plate. The SAC is a complex machinery regulated by a number of members which are rarely mutated in tumors. Rather, checkpoint components have been found to be upregulated in aneuploid tumor cells, suggesting a potential tumor “addiction” to SAC functions. MPS1 kinase, (also known as TTK) is an essential enzyme of the SAC complex which is aberrantly overexpressed in a wide range of tumors and necessary for tumor cell proliferation. We previously reported the identification of NMS-P715, a selective and orally bioavailable MPS1 inhibitor, capable of promoting mitotic acceleration, thereby causing massive aneuploidy and cancer cell death both in vitro and in vivo and which promotes tumor growth inhibition in preclinical cancer models. Supported by these results, a lead optimization program was then undertaken which led to the identification of NMS-P153, an optimized product candidate for clinical development. NMS-P153 is selective, shows high in vitro enzymatic potency on MPS1 (IC50 of 3 nM) and a prolonged residence binding time. More than 100 cell lines have been analyzed against NMS-P153 in proliferation studies and several distinct xenograft models have been tested in vivo, allowing the identification of potential genetic contexts of sensitivity. Potent anti-proliferative activity, good tumor growth inhibition associated with tumor regression and biomarker modulation was observed in sensitive xenograft models. A favorable ADME profile, associated with permissive therapeutic safety margins observed in different species at efficacious exposures, indicate that NMS-P153 is suitable for further development, with the potential for being a first-in-class drug targeting MPS1 kinase. Citation Format: Riccardo Colombo, Marina Caldarelli, Maria Laura Giorgini, Anna Degrassi, Marina Ciomei, Daniele Pezzetta, Dario Ballinari, Alessia Montagnoli, Enrico Pesenti, Daniele Donati, Arturo Galvani. Targeting aneuploidy with NMS-P153, a tight binder inhibitor of the spindle assembly checkpoint MPS1 (TTK) kinase. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2097. doi:10.1158/1538-7445.AM2013-2097
Predictors of the Feasibility of Primary Endoscopic Management of Biliary Strictures After Adult Living Donor Liver Transplantation (2011)

Biliary strictures are a major cause of morbidity and mortality for liver transplant recipients. The endoscopic management of biliary strictures is not well established after living donor liver transplantation (LDLT) in comparison with deceased donor liver transplantation. The aims of this study were to assess the initial success rate of primary endoscopic treatment of biliary strictures after LDLT and to identify predictors of the feasibility of endoscopic management. One hundred thirty-seven adult patients who underwent LDLT and were confirmed to have biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP) were enrolled. The biliary strictures were primarily managed endoscopically with internal drainage or nasobiliary catheterization. The initial success rate for the primary endoscopic management of biliary strictures after LDLT was 46.7% (64 of 137 patients), and the feasibility of endoscopic management was associated with the stricture-to-ERCP interval (the interval between the development of the total bilirubin, aspartate aminotransferase, or alanine aminotransferase level to >2 times the upper limit of normal and the performance of ERCP) as well as cholangiographic findings (eg, the stricture morphology and the tip shape of the distal duct). In conclusion, when biliary strictures are noticed after LDLT, prompt endoscopic interventions may improve the initial success rate of primary endoscopic management. In addition, the feasibility of primary endoscopic management can be predicted by the cholangiographic findings, which may help with the choice of the therapeutic modality.
The Architecture of the Butterfly Plus Parallel Processor (1988)

This paper investigates the architecture of the Butterfly Plus Parallel processor, an MIMD shared-memory machine based on the Motorola MC68020 microprocessor and a multi-stage interconnection network. The primary emphasis is on the interaction of components of the system rather than on the details of its components, especially the standard Motorola components. However, particular attention is paid to the memory management issues since this is the significant difference between the Butterfly Plus and its predecessor, the Butterfly Parallel Processor.
Abstract P6-20-17: Targeting SHP2 for the treatment of HER2-positive breast cancer (2019)

Abstract Approximately 20% of breast cancer (BC) is caused by overexpression of the human epidermal growth factor receptor 2 (HER2). As a result, several antibody-based and small molecule-based anti-HER2 therapies have been developed. These drugs have benefited BC patients by improving overall survival and quality of life. However, development of resistance and disease recurrence have been the major clinical challenges. One way to overcome these clinical problems is to develop alternative therapeutic strategies. Multiple lines of evidence show that targeting the Src homology phosphotyrosyl phosphatase 2 (SHP2) in HER2-positive BC may prove beneficial both in treatment-naïve and anti-HER2 therapy-resistant forms of the disease. For instance, silencing SHP2 expression in HER2-positive breast cancer cells or conditional knockout in ErbB2 transgenic mice blocks HER2 overexpression and associated signaling, leading to loss of cell transformation and tumorigenesis. To test the clinical translational significance of SHP2 targeting, we have invented a specific small molecule SHP2 inhibitor named WGMDY (US 9,932,288) that has shown promising anti-cancer effects. The results obtained so far show that inhibition of SHP2 with WGMDY blocks HER2 expression, suppresses cell proliferation and anchorage independent growth, and induces regression of preformed xenograft tumors. These findings suggest that SHP2 might be an excellent drug target for HER2-positive BC and WGMDY has a promising potential to serve as a lead compound for developing anti-SHP2 drugs. Citation Format: Agazie Y, Hartman Z. Targeting SHP2 for the treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-17.
Evolution and Diversity of Assembly-Line Polyketide Synthases (2019)

Assembly-line polyketide synthases (PKSs) are among the most complex protein machineries known in nature, responsible for the biosynthesis of numerous compounds used in the clinic. Their present-day diversity is the result of an evolutionary path that has involved the emergence of a multimodular architecture and further diversification of assembly-line PKSs. In this review, we provide an overview of previous studies that investigated PKS evolution and propose a model that challenges the currently prevailing view that gene duplication has played a major role in the emergence of multimodularity. We also analyze the ensemble of orphan PKS clusters sequenced so far to evaluate how large the entire diversity of assembly-line PKS clusters and their chemical products could be. Finally, we examine the existing techniques to access the natural PKS diversity in natural and heterologous hosts and describe approaches to further expand this diversity through engineering.
Election 1982 (1982)

The 1982 Congressional elections promise to be unusually hard fought. Important in themselves, they will also, inevitably, be seen as a referendum on the policies of a man whose name will not appear on the ballot: Ronald Reagan.What should voters be thinking about as they go to the polls on November 4? We have asked five Bulletin contributors to consider this question. Each addresses a particular area of concern to the magazine and its readers. Christopher Paine reviews the record of the Ninety-seventh Congress on arms control issues. John Isaacs discusses the role of the nuclear freeze campaign in the elections. Carl Marcy suggests how voters might best conceive of the long-range security needs of the United States in relation to the Soviet Union. Edwin Clark assesses Congressional stewardship of the environment. And Jamie Kalven discusses the performance of the Congress on questions of secrecy and security.These commentaries should not be construed as endorsements of particular candidates by the Bulletin, the authors speak for themselves. Rather, the pages which follow are intended to inform and provoke. Our hope is that they will contribute to the process of study and reflection by which practicing citizens determine how they will vote.THE EDITORS
Recent progress in commercial cryogen-free THz detectors and large format arrays (2010)

We report recent progress toward commercial cryogen-free THz detector systems. We discuss cryogen free cooling platform options and their applicability not only for traditional semiconductor detectors but also for new superconducting detector technologies in both single pixel and large array format.
Base-Station Assisted Device-to-Device Communications for\n High-Throughput Wireless Video Networks (2013)

We propose a new scheme for increasing the throughput of video files in\ncellular communications systems. This scheme exploits (i) the redundancy of\nuser requests as well as (ii) the considerable storage capacity of smartphones\nand tablets. Users cache popular video files and - after receiving requests\nfrom other users - serve these requests via device-to-device localized\ntransmissions. The file placement is optimal when a central control knows a\npriori the locations of wireless devices when file requests occur. However,\neven a purely random caching scheme shows only a minor performance loss\ncompared to such a genie-aided scheme. We then analyze the optimal\ncollaboration distance, trading off frequency reuse with the probability of\nfinding a requested file within the collaboration distance. We show that an\nimprovement of spectral efficiency of one to two orders of magnitude is\npossible, even if there is not very high redundancy in video requests.\n
Design, Synthesis, and Pharmacological Evaluation of a Novel Series of Pyridopyrazine-1,6-dione γ-Secretase Modulators (2014)

Herein we describe the design and synthesis of a novel series of γ-secretase modulators (GSMs) that incorporates a pyridopiperazine-1,6-dione ring system. To align improved potency with favorable ADME and in vitro safety, we applied prospective physicochemical property-driven design coupled with parallel medicinal chemistry techniques to arrive at a novel series containing a conformationally restricted core. Lead compound 51 exhibited good in vitro potency and ADME, which translated into a favorable in vivo pharmacokinetic profile. Furthermore, robust reduction of brain Aβ42 was observed in guinea pig at 30 mg/kg dosed orally. Through chemical biology efforts involving the design and synthesis of a clickable photoreactive probe, we demonstrated specific labeling of the presenilin N-terminal fragment (PS1-NTF) within the γ-secretase complex, thus gaining insight into the binding site of this series of GSMs.
Alzheimer β-Amyloid Homodimers Facilitate Aβ Fibrillization and the Generation of Conformational Antibodies (2003)

We reported previously that stabilized beta-amyloid peptide dimers were derived from mutant amyloid precursor protein with a single cysteine in the ectodomain juxtamembrane position. In vivo studies revealed that two forms of SDS-stable A beta homodimers exist, species ending at A beta 40 and A beta 42. The phenomenon of the transformation of the initially deposited 42-residue beta-amyloid peptide into the amyloid fibrils of Alzheimer's disease plaques remains to be explained in physical terms, i.e. energetically and structurally. We therefore performed spectroscopic analyses revealing that engineered dimeric peptides ending at residue 42 displayed a much more pronounced beta-structural transition than corresponding monomers. Specifically, the single chemically induced dimerization of A beta peptides significantly increased the beta-sheet content by a factor of 2. The C-terminal residues Ile-41 and Ala-42 of dimeric forms further increased the beta-sheet content by roughly one-third. In contrast to A beta 42, the beta-sheet content of the alpha- and gamma-secretase-generated p3 fragments did not necessarily correlate with the tendency to form fibrils, although p3/17-42 had a pronounced thread forming character with fibril lengths of up to 2.5 microM. Electron microscopic images show that forms of p3/17-42 generated smaller granular particles than forms ending at residue 40. We discuss these findings in terms of A beta 1-42 dimers representing paranuclei, which self-aggregate into ribbon-like ordered fibrils by elongation. Based on A beta 42 dimer-specific titers of a polyclonal antiserum we propose that the A beta homodimer represents a nidus for plaque formation and a well defined novel therapeutic target.
Nonlinear Model Learning for Compensation and Feedforward Control of Real-World Hydraulic Actuators Using Gaussian Processes (2022)

This paper presents a robust machine learning framework for modeling and control of hydraulic actuators. We identify several important challenges concerning learning accurate models of the dynamics for real machines, including noise and uncertainty in state measurements, nonlinear effects, input delays, and data-efficiency. In particular, we propose a dual-Gaussian process (GP) model architecture to learn a surrogate dynamics model of the actuator, and showcase the accuracy of predictions against the piecewise and neural network models that have been widely used in the literature. In addition, we provide robust techniques for learning neural network inverse models and controllers by batch GP inference in an automated, seamless and computationally fast manner. Finally, we demonstrate the performance of the trained controllers in real-world feedforward and tracking control applications.
Photonic crystal waveguides based on an antiresonant reflecting platform (2005)

We apply the antiresonant reflecting layers arrangement to silicon-on-insulator based photonic crystal waveguides. Several layered structures with different combinations of materials (Si-SiO/sub 2/, Si/sub 3/N/sub 4/-SiO/sub 2/) and layer topology have been analysed. Numerical modelling using the 3D finite-difference time-domain method reveals promising low-loss results with potential for competing with membrane-like photonic crystal waveguides.
Shared Cloud Object Store, governed by permissioned blockchain (2018)

No abstract available.
Apparent Proximal Ulna Dorsal Angulation Variation Due to Ulnar Rotation (2019)

This study demonstrates that small degrees of ulna rotation result in a statistically significant change in the apparent PUDA; however, this may not represent a clinically significant difference. Because of the anatomic variation between patients, it is important to obtain a contralateral film to determine the PUDA for anatomic reduction of the ulna in complex cases. When using a contralateral image, it is important to obtain a true lateral film or consider using 3-dimensional imaging for preoperative planning.
Demonstration of a multipulse interferometer for quantum kicked-rotor studies (2009)

We implemented a multipulse interferometer scheme that allows us to study a quantum kicked rotor by observing dephasing of momentum coherence. Our study shows that momentum coherence can be nearly perfectly preserved under conditions where the mean energy as a function of the kick number is known to increase without bound. The accompanying width narrowing of these coherences may provide a new method for accurate measurement of the recoil frequency.
ChemInform Abstract: KETENE THIOACETAL ROUTE TO Γ‐LACTONES. EFFECT OF CARBONYL HARDNESS ON REACTION‐SITE SELECTIVITY AND A UNIQUE PREPARATION OF 3‐METHYL‐5‐PHENYL‐2(5H)‐FURANONE (1980)

Abstract ′IUU I0 Ketene Thioacetal Route to "y‐Lactones.
Mercuric iodide thick films for radiological x-ray detectors (2000)

For the first time polycrystalline HgI2 photoconductor material directly evaporated on a-Si array for direct conversion of x-rays for imaging purposes, were successfully imaged at Xerox-Palo Alto Research Center. The initial results are very promising and show a high x-ray sensitivity and low leakage current. Since Ti-W alloys are used as pixel electrodes, an intermediate passivation layer must be used to prevent a chemical reaction with the detector plate. The thickness that these Polycrystalline HgI2 thick film detectors have been fabricated until now is up to 1,800 micrometers , which makes them useful also for high energy applications. The characterization of the Polycrystalline HgI2 thick films deposited with or without the passivation layers by measuring their dark currents, sensitivity to 65 and 85 kVp x-rays and residual signals after 1 minute of biasing, will be shown for several detectors. Some preliminary results will be shown for some novel screen-printed HgI2 detectors.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
ACCUMULATION OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) AND HIGH MOBILITY GROUP BOX CHROMOSOMAL PROTEIN-1 (HMGB-1) IN THE LUNG DURING SEPSIS; IMPLICATIONS FOR CARDIAC FUNCTION. (2004)

Miller, E. J.; Lin, X.; Al-Abed, Y.; Metz, C.; Wang, H.; Ojaama, K.; Sakuragi, T.; Hu, M.; Powell, S.; Wang, P.; Simms, H. H. Author Information
Abstract 4914: Role of ClpP in the anti-cancer effects of imipridone ONC201 and ONC206 (2023)

Abstract ONC201 is the first bitopic dopamine receptor D2 (DRD2) antagonist and allosteric mitochondrial protease ClpP agonist. Downstream of target engagement, ONC201 activates the integrated stress response pathway resulting in selective tumor cell death. ONC201 is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC206, a derivative of ONC201 currently in Phase I trials for adult and pediatric brain tumors, is also a bitopic DRD2 antagonist and ClpP agonist with nanomolar potency. We further evaluated in vitro efficacy and mechanism of action specific to ClpP for ONC206 and investigated acquired resistance to ONC201 and ONC206. FITC-casein and peptide degradation assays confirmed that ONC206 acts as an agonist of human ClpP with enhanced potency relative to ONC201. Broad efficacy in the nanomolar range for ONC206 (GI50 &amp;lt;78-889nM, 72h) was observed in 1,088 Genomics of Drug Sensitivity in Cancer (GDSC) cancer cell lines with increased sensitivity in cell lines exhibiting high ClpP mRNA expression. Among solid tumors, nervous system-related cell lines were particularly sensitive. Gene Expression Profiling Interactive Analysis (GEPIA) database analysis showed ClpP mRNA was overexpressed in glioblastoma cells relative to normal cells. GDSC observations were confirmed in glioblastoma (GBM) (T98G, A172, U87MG), H3.3 K27M mutant diffuse intrinsic pontine glioma (DIPG) (SF8628, SF7761) and astrocytoma (H4, U118MG) cell lines. ONC206 was more potent than ONC201 in cell viability assays for all glioma lines tested. SF8628 cells with a CRISPR-mediated ClpP knockout were shown to demonstrate resistance to both ONC201 and ONC206. Polyclonal resistant cell lines were generated through prolonged passaging in increasing concentrations of ONC201 or ONC206 (SF8628 and T98G cells). Cells with acquired resistance to ONC201 (ONC201Res) or ONC206 (ONC206Res) showed cross resistance to both imipridones. Time-stability of resistance was confirmed by removing drug for 2 to 4 weeks and retesting. RNAseq analysis revealed upregulation of the integrated stress response with imipridone treatment in T98G parental cells but not resistant clones. Whole genome sequencing revealed ClpP mutations in both ONC201Res and ONC206Res cells. Our results confirm the role of ClpP in the mechanism of action of ONC201 and ONC206 in tumor cells. Citation Format: Andrew Lee, Cristina Maranto, Scott Foster, Sara Morrow, Joshua E. Allen, Randall Lanier, Phiroze Sethna, Varun V. Prabhu. Role of ClpP in the anti-cancer effects of imipridone ONC201 and ONC206. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4914.