gebhart/patrepeval huggingface dataset:
Regulation of macrophage eicosanoid production by hydroperoxy-and hydroxy-eicosatetraenoic acids (1986)

Resident mouse peritoneal macrophages when exposed to zymosan during the first day of cell culture synthesize and secrete large amounts of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), the respective products of cyclo-oxygenase- and 5-lipoxygenase-catalysed oxygenations of arachidonic acid. Under these conditions of cell stimulation only small amounts of hydroxyeicosatetraenoic acids (HETEs) are concomitantly produced. However, exogenously added arachidonic acid is metabolized to large amounts of 12- and 15-HETE and only relatively small amounts of PGE2. No LTC4 is formed under these conditions. In contrast, resident mouse peritoneal macrophages in cell culture for 4 days synthesized less PGE2 and LTC4 when exposed to zymosan. However, these macrophage populations continue to synthesize 12-HETE from exogenously added arachidonic acid. Zymosan induced the secretion of a lysosomal enzyme, N-acetyl-beta-glucosaminidase, equally in both 1- and 4-day cultures. Both 12- and 15-hydroperoxyeicosatetraenoic acids (HPETEs), the precursors of 12- and 15-HETE, were found to be irreversible inhibitors of the cyclo-oxygenase pathway and reversible inhibitors of the 5-lipoxygenase pathway in macrophages. 15-HETE were found to be reversible inhibitors of both pathways. Thus the oxidation of arachidonic oxidation of arachidonic acid to both prostaglandins and leukotrienes may be under intracellular regulation by products of 12- and 15-lipoxygenases.
Facile Synthesis of Functionalized Lactones and Organocatalytic Ring-Opening Polymerization (2012)

A facile one-step synthesis of functionalized valerolactones was carried out by the conjugate addition of thiols to the α,β-unsaturated valerolactone 5,6-dihydro-2<i>H</i>-pyran-2-one. The resultant 3-mercaptovalerolactones undergo ring-opening polymerization in solution or in the melt to generate polyesters functionalized either with benzyl mercaptans or oligoethylene glycol pendant groups. The copolymerization of the 3-mercaptovalerolactones with ε-caprolactone generates random copolymers.
Zombie Survival Optimization: A Swarm Intelligence Algorithm Inspired By Zombie Foraging (2015)

Search optimization algorithms have the challenge of balancing between exploration of the search space (e.g., map locations, image pixels) and exploitation of learned information (e.g., prior knowledge, regions of high fitness). To address this challenge, we present a very basic framework which we call Zombie Survival Optimization (ZSO), a novel swarm intelligence ap-proach modeled after the foraging behavior of zombies. Zombies (exploration agents) search in a space where the underlying fitness is modeled as a hypothetical air-borne antidote which cures a zombie’s aliments and turns them back into humans (who attempt to survive by exploiting the search space). Such an optimization al-gorithm is useful for search, such as searching an image for a pedestrian. Experiments on the CAVIAR dataset suggest improved efficiency over Particle Swarm Op-timization (PSO) and Bacterial Foraging Optimization (BFO). A C++ implementation is available. 1
Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies (2011)

Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer.
386 Phase I/Ib first-in-human study of HEK-NIZ985, a recombinant IL-15/IL-15Rα heterodimer, alone and in combination with spartalizumab, in adults with advanced and metastatic solid tumors (2020)

<h3>Background</h3> HEK-NIZ985 (NIZ985) is a recombinant heterodimer of IL-15/IL-15Rα that expands effector lymphocytes and antitumor activity in animal models and a human clinical trial. We report interim data from the first-in-human study of NIZ985. <h3>Methods</h3> CNIZ985X2102J is an open-label Phase I/Ib dose-escalation/expansion trial evaluating the safety of subcutaneous NIZ985 three-times-weekly (TIW; 2-weeks-on/2-weeks-off) or once-weekly (QW; 3-weeks-on/1-week-off) as a single agent (SA) or in combination (CM) dosing with 400 mg of the PD-1 inhibitor spartalizumab every 4 weeks, in adults with metastatic/unresectable solid tumors. SA dosing was 0.25–4 µg/kg TIW or 2–10 µg/kg QW; CM dosing was 1 µg/kg TIW or 2–4 µg/kg QW. The primary objective was to characterize the safety and tolerability of NIZ985 ± spartalizumab. Data are presented for dose escalation, and CM-TIW expansion. <h3>Results</h3> Overall, 83 patients entered dose escalation (n=47) or CM-TIW expansion (n=36), of whom 63.8% (30/47) and 69.4% (25/36), respectively, had received ≥3 prior lines of antineoplastic treatment. At data cut-off (March 2, 2020), 91.6% (76/83) had discontinued study treatment. Adverse events (AEs) are summarized below (table 1). There were no dose-limiting toxicities during the first 28-day cycle in any cohort. Systemic skin AEs (Cycle 2) occurred in three SA-TIW patients receiving 2 or 4 µg/kg (bullous pemphigoid, purpura, vasculitis), limiting TIW escalation and initiating QW dose exploration; these were not observed at 1 µg/kg TIW (± spartalizumab) or for QW doses up to 10 µg/kg. CM-TIW dose expansion was therefore at 1 µg/kg; the recommended QW expansion dose is currently undetermined. For SA NIZ985, best overall response (RECIST 1.1) was stable disease (SD; 8/27 patients [29.6%]). Objective responses for NIZ985 plus spartalizumab (3/56 partial response [PR; 5.3%], 15/56 SD [26.8%]) occurred in both immuno-oncology treatment (IO)-naïve and IO-experienced patients, including 5/8 IO-experienced melanomas (cutaneous: 3 SD, 1 PR; uveal: 1 SD). Systemic NIZ985 exposure was approximately dose-proportional after first dose for ≥1 µg/kg TIW and &lt;10 µg/kg QW, with time-dependent clearance without accumulation. Proliferation of peripheral CD8+ and NK lymphocytes, and increased inflammatory cytokines, were observed for both dosing schedules. <h3>Conclusions</h3> NIZ985 is safe and tolerable at both TIW and QW dosing ± spartalizumab. It displays approximately dose-proportional, time-dependent PK, and a biomarker and lymphocyte response profile consistent with target engagement. Limited antitumor activity was reported during dose escalation; however, preliminary responses in both IO-experienced and IO-naïve patients were seen in combination with spartalizumab that warrant further investigation. <h3>Ethics Approval</h3> The study was approved by an independent ethics committee and/or institutional review board at each participating site.
Downlink MIMO in LTE-advanced: SU-MIMO vs. MU-MIMO (2012)

Single-user multi-antenna technologies are well upported in current standard specifications like LTE Release 8/9. Further development of the specification (LTE-Advanced) is expected to conform to the requirements for IMT-Advanced systems. One of the key enabling features of LTE-Advanced to meet IMT-Advanced downlink performance requirements is multi-user MIMO, where a transmitter serves multiple users simultaneously on the same frequency resource, primarily relying on spatial separation. In general, multi-user MIMO is beneficial for improving average user spectral efficiency. However, cell edge user spectral efficiency may be reduced if multi-user MIMO is used exclusively, due to residual inter-user interference arising from practical multi-user beamforming and reduced transmit power allocated to each user. Therefore, it should be possible to configure the UE-specific transmission mode to support dynamic switching between single-user MIMO and multi-user MIMO to balance the cell edge user spectral efficiency as well as the average cell user spectral efficiency. In this article, we study various aspects of multi-user MIMO including design philosophy, multi-user precoding, and control signaling. The associated feedback schemes, including those that facilitate dynamic switching, are discussed. Performance evaluation is conducted to demonstrate the gain of dynamically switched single-user and multiuser MIMO as opposed to traditional single-user MIMO.
An integrative modeling framework to evaluate the productivity and sustainability of biofuel crop production systems (2010)

Abstract The potential expansion of biofuel production raises food, energy, and environmental challenges that require careful assessment of the impact of biofuel production on greenhouse gas (GHG) emissions, soil erosion, nutrient loading, and water quality. In this study, we describe a spatially explicit integrative modeling framework (SEIMF) to understand and quantify the environmental impacts of different biomass cropping systems. This SEIMF consists of three major components: (1) a geographic information system (GIS)‐based data analysis system to define spatial modeling units with resolution of 56 m to address spatial variability, (2) the biophysical and biogeochemical model Environmental Policy Integrated Climate (EPIC) applied in a spatially‐explicit way to predict biomass yield, GHG emissions, and other environmental impacts of different biofuel crops production systems, and (3) an evolutionary multiobjective optimization algorithm for exploring the trade‐offs between biofuel energy production and unintended ecosystem‐service responses. Simple examples illustrate the major functions of the SEIMF when applied to a nine‐county Regional Intensive Modeling Area (RIMA) in SW Michigan to (1) simulate biofuel crop production, (2) compare impacts of management practices and local ecosystem settings, and (3) optimize the spatial configuration of different biofuel production systems by balancing energy production and other ecosystem‐service variables. Potential applications of the SEIMF to support life cycle analysis and provide information on biodiversity evaluation and marginal‐land identification are also discussed. The SEIMF developed in this study is expected to provide a useful tool for scientists and decision makers to understand sustainability issues associated with the production of biofuels at local, regional, and national scales.
Effects of genistein on β‐catenin signaling and subcellular distribution of actin‐binding proteins in human umbilical CD105‐positive stromal cells (2010)

This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca(2+) and attenuated cell proliferation and DNA synthesis through the beta-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-beta-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca(2+) and rendered genistein resistance in decreasing intracellular Ca(2+) in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.
Membrane organization in G‐protein mechanisms (1994)

A prevailing view of receptor and G-protein function in cells includes random collisions between the proteins with a great specificity at the sites of protein-protein interaction. Recent evidence suggests that receptors, G-proteins, and effectors may be less mobile and that these systems are more highly organized than previously appreciated. Several types of evidence suggest that receptors do not have free access to all G-protein with which they are capable of coupling. Also, the specificity of signaling in intact cells appears to be significantly greater than in reconstituted systems. The distribution and mobility of G-proteins in cells are restricted to a surprising degree. Thus, complex interactions of the receptors and G-proteins with their effectors and cell membrane machinery appear to play an important role in their function. A full understanding of G-protein-coupled receptors must include a better description of the organization of these systems in cell membranes. Possible roles for noncoated pits (caveolae) and a novel pleckstrin homology domain need to be examined.
High Oxidation Tolerance of Ru Nanoparticles on 12CaO·7Al2O3 Electride (2016)

A high tolerance to oxidation of Ru nanoparticles loaded on 12CaO·7Al2O3 (C12A7) was examined by in situ X-ray absorption fine structure (XAFS). Ru nanoparticles on electron-doped C12A7 (C12A7:e–) and stoichiometric C12A7 (C12A7:O2–) are robust to oxidation, while those on Al2O3 and on MgO with Cs promoters are easily oxidized. The oxidation tolerance is higher for Ru/C12A7:e– than Ru/C12A7:O2–. The main factor of the oxidation tolerance comes from the electron donation property of C12A7:e–. C12A7:e– is an electride in which electrons serve as anions, and these anionic electrons with a low work function (2.4 eV) have a high ability to donate electrons to supporting Ru nanoparticles with a higher work function (4.7 eV). Electron transfer from C12A7:e– maintains Ru nanoparticles in the metallic state even under oxidation condition. The Ru catalysts on C12A7:e– with high oxidation tolerance can be applied to various catalytic reactions under oxygen-rich conditions, in which conventional catalysts are rapidly oxidized.
Liver Tropism and Factor VIII Transgene Expression after Intrauterine Chorionic Villus Stem Cell Transplantation (2015)

Abstract INTRODUCTION: Gestation is characterized by rapid mitosis and histogenesis in an immune naïve environment. Growth and development of vital organs are occurring continuously at different time points throughout pregnancy under the regulation of paracrine signals, transcription and growth factors. Appropriate timing to target the developing organ of interest during in utero stem cell transplantation (IUT) may result in high level engraftment in that organ as well as recognition of foreign cells as self. Hemophilia A, is an X-linked recessive bleeding disorder caused by a mutation of the gene that encodes Factor VIII (FVIII) which is primarily produced by the liver. We hypothesize that introduction of stem cells in utero during hepatogenesis in mice (e9.5-15 days) will result in localization and persistence of stem cells in the liver. METHODOLOGY: We reported isolation and characterization of early preterm chorionic villus derived mesenchymal stem cells (PMSCs) at GA 9-13 weeks. PMSCs (n =5) were transduced with a lentiviral vector encoding B-domain deleted FVIII, GFP and luciferase reporter genes (pCCLc-MNDU3-eGFP/LUC-PGK-F8-WPRE) at an MOI (Multiplicity of Infection) of 3. Chromogenic assay was performed on cell supernatant of transduced PMSCs 72 hours after transduction. Prior to transplantation, PMSCs were plated at different densities ranging from 250,000 cells to 2 x10^6 cells and subjected to bioluminescence imaging. Intraperitoneal transplantation of PBS (control group) or with 1 x10^6 PMSCs (experimental group) was conducted in fetal mice at e12-14 days using a 33 gauge non-coring needle. Bioluminescence analysis was performed 24 hours after IUT on dams, and 12-15 days after transplantation. Mice were euthanized and liver tissue was harvested from all animals. Expression of FVIII was analyzed by RT-PCR from both groups. RESULTS: Bioluminescence imaging revealed focal density and transgene expression for transduced cells in vitro, in vivo at 24 hours and in postnatal pups 12-14 days after transplantation. Postmortem bioluminescence analysis of IUT transplanted mice showed positive bioluminescence in the livers of pups injected with transduced PMSCs. RT-PCR analysis of the liver samples using human specific FVIII primers revealed FVIII expression in liver tissues in PMSC treated mice while negative for PBS treated mice. CONCLUSION: These results demonstrate the functional survival and localization of genetically modified PMSCs in the liver after intrauterine transplantation for up to two weeks. This study provide better understanding of the cell fate of stem cells after IUT and suggest that appropriate timing of stem cell transplantation in utero may lead to immunological tolerance. Disclosures Powell: CSL Behring: Employment.
Generation of the Glycyl Radical of the Anaerobic Escherichia coli Ribonucleotide Reductase Requires a Specific Activating Enzyme (1995)

The anaerobic ribonucleotide reductase from Escherichia coli contains a glycyl radical as part of its polypeptide structure. The radical is generated by an enzyme system present in E. coli. The reductase is coded for by the nrdD gene located at 96 min. Immediately downstream, we now find an open reading frame with the potential to code for a 17.5-kDa protein with sequence homology to a protein required for the generation of the glycyl radical of pyruvate formate lyase. The protein corresponding to this open reading frame is required for the generation of the glycyl radical of the anaerobic reductase and binds tightly to the reductase. The "activase" contains iron, required for activity. The general requirements for generation of a glycyl radical are identical for the reductase and pyruvate formate lyase. For the reductase, the requirement of an iron-containing activase suggests the possibility that the iron-sulfur cluster of the enzyme is not involved in radical generation but may participate directly in the reduction of the ribonucleotide.
ChemInform Abstract: REACTIONS OF COORDINATED LIGANDS. PART 32. THE REACTION OF SULFUR NUCLEOPHILES WITH CATIONIC MOLYBDENUM ALKYNE COMPLEXES: ALKYNE ROTATION AND THE MOLECULAR STRUCTURE OF THE COMPLEXES (MO(SC6H4NO2‐P)(P(OME)3)(η2‐MEC2ME)(η‐C5H5)) AND (MO(SC6H4SPH‐O)(CO)(η2‐MEC2ME)(η‐C5H5)) (1985)

Abstract An den Produkten (II) der Reaktion des kationischen Mo‐Alkin‐Komplexes (I) mit in situ dargestellten Nathiolaten wurde die Rotation der Alkinliganden im Zusammenhang mit den elek‐ 141 tronischen Einflüssen durch die Thiolatsubstituenten untersucht.
Group Carrier Supply Ceramic Filter (1984)

A group carrier supply ceramic filter for use in an FDM carrier system was examined. For the filter, a ladder filter configuration composed of nine wire-mounted ceramic disk resonators and eight multilayer ceramic capacitors was adopted. Because of refinement of the filter design, only rough adjustment was fully sufficient for the frequency adjustment on the resonator. The filter exhibited analogous characteristics designed according to image parameter theory; both its temperature and aging characteristics were satisfactory. The stopband attenuation was more than 100 dB, due to suppression of spurious vibration. The filter size was reduced to 1/2 that of the usual quartz crystal filter.
MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century (2009)

The essence and origin of malignant fibrous histiocytoma (MFH) have been debated for now close to five decades. Originally characterized as a morphologically unique soft-tissue sarcoma subtype of unclear etiology in 1963, with a following 15 years of research only to conclude that "the issue of histogenesis [of MFH] is largely unresolvable"; it is "now regarded as synonymous with [high grade] undifferentiated pleomorphic sarcoma and essentially represents a diagnosis of exclusion". Yet despite this apparent lack of progress, the first decade of the 21st century has seen some significant progress in terms of defining the origins of MFH. Perhaps more importantly these origins might also pave the way for novel therapies. This manuscript will highlight MFH's troubled history, discuss recent advances, and comment as to what the coming years may promise and what further needs to be done to make sure that progress continues.
A numerical investigation of direct and indirect closed-loop architectures for estimating nonminimum-phase zeros (2018)

This paper presents a numerical investigation of three direct architectures and three indirect architectures for identifying a plant operating in closed loop. Motivated by adaptive control of systems with nonminimum-phase (NMP) zeros and taking advantage of the fact that zeros are not moved by feedback, the performance metric is the accuracy of the estimates of the NMP zeros of the plant. Assuming known plant order, single-input, single-output, infinite-impulse-response models are constructed in the presence of process and sensor noise. Least squares provides the baseline estimation technique, and prediction error methods are used to account for correlation between the model input and noise. The goal is to compare the accuracy of the NMP-zero estimates obtained from each method and for each architecture.
Cladding Glass Development for Semiconductor Core Optical Fibers (2012)

Cladding glass compositions have been developed to minimize thermal expansion mismatch in the glass clad crystalline core fibers. These tailored compositions have also shown to reduce oxygen content in the fibers.
Outcome-Driven Reinforcement Learning via Variational Inference (2021)

While reinforcement learning algorithms provide automated acquisition of optimal policies, practical application of such methods requires a number of design decisions, such as manually designing reward functions that not only define the task, but also provide sufficient shaping to accomplish it. In this paper, we view reinforcement learning as inferring policies that achieve desired outcomes, rather than as a problem of maximizing rewards. To solve this inference problem, we establish a novel variational inference formulation that allows us to derive a well-shaped reward function which can be learned directly from environment interactions. From the corresponding variational objective, we also derive a new probabilistic Bellman backup operator and use it to develop an off-policy algorithm to solve goal-directed tasks. We empirically demonstrate that this method eliminates the need to hand-craft reward functions for a suite of diverse manipulation and locomotion tasks and leads to effective goal-directed behaviors.
EMPREGO DE ANTIINFLMATÓRIOS NÃO ESTEROIDAIS NO TRATAMENTO DA ARTRITE REUMATÓIDE (2012)

A terapia farmacologica e o principal tratamento para os pacientes com AR. Ela varia de acordo com o estagioda doenca, atividade e gravidade, por isso para o controle da dor e do processo inflamatorio sao empregados os analgesicos, os AINEs e os anti‑inflamatorios esteroides.