gebhart/patrepeval huggingface dataset:
Fasiglifam (TAK-875) alters bile acid homeostasis in rats and dogs: a potential cause of drug induced liver injury (2017)

Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations. Repeat dose studies determined that TAK-875 caused a dose-dependent increase in serum total BA in rats and dogs. Additionally, there were dose-dependent increases in both unconjugated and conjugated individual BAs in both species. Rats had an increase in serum markers of liver injury without correlative microscopic signs of tissue damage. Two of 6 dogs that received the highest dose of TAK-875 developed liver injury with clinical pathology changes, and by microscopic analysis had portal granulomatous inflammation with neutrophils around a crystalline deposition. The BA composition of dog bile also significantly changed in a dose-dependent manner following TAK-875 administration. At the highest dose, levels of taurocholic acid were 50% greater than in controls with a corresponding 50% decrease in taurochenodeoxycholic acid. Transporter inhibition by TAK-875 may cause liver injury in dogs through altered bile BA composition characteristics, as evidenced by crystalline deposition, likely composed of test article, in the bile duct. In conclusion, a combination of in vitro and in vivo evidence suggests that BA transporter inhibition could contribute to TAK-875-mediated liver injury in dogs.
Inhibition of gamma delta T cell development and early thymocyte maturation in IL-7 -/- mice (1996)

While early thymic T cell precursor populations and their maturational sequence have been recently identified, the signals driving differentiation are unknown. While cytokines may play an integral role in T cell development, various mouse models rendered genetically deficient for specific cytokines do not display abnormalities in T cell development. Recently, we have generated IL-7 -/- mice and reported that IL-7 plays a unique and nonredundant role in lymphopoiesis. These mice displayed a 10- to 20-fold reduction in the total number of T and B cells. Here, we show that IL-7 -/- mice display a sharp reduction in both the frequency and absolute number of adult thymic gamma delta T cells while retaining normal frequencies of alpha beta T cells. This defect in gamma delta T cell production extends to peripheral organs as IL-7 -/- mice are essentially devoid of splenic and intestinal intraepithelial gamma delta T cells. This aberrant phenotype was traced back to impaired fetal gamma delta T cell maturation. In the absence of IL-7, differentiation of immature V gamma 3 low-CD24+ fetal T cells to mature V gamma 3 high CD24- cells is inhibited. In contrast, NK cell maturation appears to be only mildly affected in the absence of IL-7. To further clarify the role of IL-7 in thymic development, detailed analysis of CD3-4-8- thymic precursors was performed. A partial inhibition in the differentiation of CD44+25+ pro-T cells into CD44-25+ pre-T cells was observed. Unexpectedly, the lack of IL-7 resulted in decreased expression of CD117 (c-kit) on both CD4 low and pro-T cells, suggesting that IL-7 may influence the expression of other cytokine receptors involved in early hemopoietic development. Together, these data clarify the developmental abnormalities during T cell development due to the absence of IL-7.
Mapeamento de informações em sistemas corporativos Uma arquitetura da informação aplicada à Embrapa (2005)

As informacoes armazenadas em sistemas computadorizados sao, geralmente, desconhecidas pela maioria dos membros de uma empresa. Muitas vezes a informacao necessaria esta disponivel, mas as pessoas nao sabem como acessa-la e nem da sua existencia. Diante desta necessidade, tratou-se a seguinte questao: como localizar as informacoes de uma organizacao a partir dos seus sistemas de informacao? Para resolve-la, foi feita uma pesquisa qualitativa, metodologica e aplicada, visando definir um mapa das informacoes armazenadas em alguns sistemas de informacao corporativos da Embrapa - Empresa Brasileira de Pesquisa Agropecuaria. Para a construcao do mapa, definiu-se um processo para sistematizar o mapeamento das informacoes. O processo e baseado em conceitos da arquitetura da informacao, na representacao por meio de metadados, na classificacao das informacoes e na relacao com os processos de negocio da empresa. A partir da aplicacao do processo proposto, foi realizado um estudo na Embrapa tendo sido mapeado tres sistemas corporativos. Foram analisados sessenta e tres relatorios e construido um mapa de informacoes. Algumas questoes podem ser respondidas atraves do mapa para melhorar a tomada de decisao e a disponibilizacao de informacoes para a organizacao, tais como: quais informacoes estao duplicadas na organizacao e onde se encontram?-; quais os relatorios que possuem uma grande quantidade de informacoes?-; quem pode ter acesso A  determinada informacao?-; quais sao os processos de negocio associados a um determinado sistema de informacao?-; qual area da organizacao e responsavel por uma informacao?-. Conclui-se que as informacoes existentes nos sistemas de informacao de uma organizacao podem ser representadas atraves de um mapa de informacoes e que este podera servir como um raio x- do seu ambiente informacional.
Fuel cells-an introduction (2001)

Fuel cell is a simple static device that converts chemical energy in a fuel directly isothermally and continuously into electrical energy. Isothermal operation enables fuel cells to completely bypass the Carnot limitation on efficiency suffered by heat engines operating between a hot side and a cold side. Thus fuel cells inherently promise higher conversion efficiencies.
Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins (2009)

Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I-like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.
Infection-Control Guidelines for Patients with the Acquired Immunodeficiency Syndrome (AIDS) (1983)

A task force* at the University of California, San Francisco, has developed infection-control guidelines for patients with the acquired immunodeficiency syndrome (AIDS). The task force included representatives of the University of California, San Francisco, and the city and county of San Francisco; administrators from various San Francisco hospitals; and other health-care workers with a special interest in AIDS. It also considered guidelines that had been developed by the infection-control committees at both University of California Moffitt Hospital† and San Francisco General Hospital.‡The purpose of this report is to present the findings of the task force and, recognizing that a . . .
Stimulation of Innate Immune Cells by Light-Activated TLR7/8 Agonists (2014)

The innate immune response is controlled, in part, by the synergistic interaction of multiple Toll-like receptors (TLRs). This multi-receptor cooperation is responsible for the potent activity of many vaccines, but few tools have been developed to understand the spatio-temporal elements of TLR synergies. In this Communication, we present photo-controlled agonists of TLR7/8. By strategically protecting the active agonist moiety based on an agonist-bound crystal structure, TLR activity is suppressed and then regained upon exposure to light. We confirmed NF-κB production upon light exposure in a model macrophage cell line. Primary cell activity was confirmed by examining cytokine and cell surface marker production in bone-marrow-derived dendritic cells. Finally, we used light to activate dendritic cell sub-populations within a larger population.
Comparison between the periodic and event-triggered intra-frequency handover measurement reporting in WCDMA (2002)

In this paper the WCDMA intra-frequency measurement reporting and handover procedure is presented, and the performance of the two main measurement reporting options, periodic and event-triggered, are compared. Furthermore, the impact of some of the parameters defined for the event-triggered mode is also studied. The comparisons are done in terms of both system quality, uplink noise rise and total base station output power, and the signaling load, i.e. the average measurement reporting and active set update rate. The system simulation results show, that the event-triggered measurement reporting scheme results in lower signaling load with the same level of system quality. Furthermore, the right choice of parameters for the event-triggered mode can improve the situation even further.
Action of plant hormones (2001)

With the evolution of specific perception mechanisms, molecules such as auxins, cytokinins, gibberellins, abscisic acid and ethylene, acquires a hormonal role during the evolution of land plants. These hormones induse cell division, cell elongation and cell differentiation by regulating the expression of transcription factors and cell type specific genes. A limited number of modules and signalling path-ways have been utilized during hormonal signal transduction. The specificity arises at the level of receptors, transciption factors, post-translational madifications of signalling agents and crosstalk between different hormones. The signalling pathways are turning out to highly conserved in plants and animals.
The relationship between visuo-spatial attention and nonword reading in developmental dyslexia (2006)

Focused visuo-spatial attention was studied in 10 developmental dyslexic children with impaired nonword reading, 10 dyslexic children with intact nonword reading, and 12 normally reading children. Reaction times to lateralized visual stimuli in a cued detection task showed that attentional facilitation of the target at the cued location was symmetrical in the three groups. However, dyslexics with impaired nonword reading selectively showed a lack of attentional inhibition for targets at the uncued location in the right visual field. This result was replicated in a second group of 13 dyslexics with impaired nonword reading. Individual differences in the ability of right attentional inhibition across the entire sample of dyslexics accounted for 17% of unique variance in nonword reading accuracy after controlling for individual differences in age, IQ, and phonological skills. A possible explanation based on the role of spatial attention mechanisms in the graphemic parsing process is discussed. Our results suggest that focused visuo-spatial attention may be crucial for nonword decoding.
The Effects of Human Peripheral Blood Mononuclear Cells on the Proliferation and Differentiation of Human Periodontal Ligament Fibroblast Cells (2007)

Objective In order to illuminate the potential effect of periodontal vascular system on the remodeling of the periodontal tissues, the author investigated the effect of human peripheral blood mononuclear cells (PBMC5) on human periodontal ligament cells (PDL cells). Methods The co-culture system of PDL cells and human PBMCs separated by transwell was established. PDL cells proliferation was determined by direct cell counting and Proliferating cell nuclear antigen (PCNA) labeling index (LI). The alkaline phosphatase (ALPase) activity of PDL cells was evaluated by enzyme kinetics methods after 1, 3, 5, 7 days. Results After co-culture, the number of PDL cells was 4.5×10^4 after 3 days and 8.5×10^4 after 5 days. Compared with the control group, the difference between the two groups and control group was significant (p＜0.05). The PCNA LI got the same result. The ALPase activities of PDL cells were reduced by co-culture with human PBMCs after 3, 5, 7 days. Conclusion Human PBMCs could induce the proliferation of PDL cells, while restrain the differentiation of PDL cells.
Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data (2001)

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO(2)) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO(2) during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [(15)O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.
On Small Characteristic Algebraic Tori in Pairing-Based Cryptography (2006)

The value ot the late pairing on an elliptic curve over a finite field may be viewed as an element of an algebraic torus. Using this simple observation, we transfer techniques recently developed for torus-based cryptography to pairing-based cryptography, resulting in more efficient computations, and lower bandwidth requirements. To illustrate the efficacy of this approach, we apply the method to pairings on supersingular elliptic curves in characteristic three.
Uplink scheduling for Machine-to-Machine communications in LTE-based cellular systems (2011)

Cellular systems are expected to play a fundamental role in the future Machine-to-Machine (M2M) networks, which could inherit crucial benefits from the former, such as ubiquitous coverage and global internetworking. However, unique features of M2M communications, such as the larger number of connected devices and the diversity of applications, require specific enhancements to these cellular systems. Because of the nature of most of M2M applications, a large number of uplink transmissions is expected, rendering uplink scheduling as an essential issue towards supporting M2M communications via cellular networks. We propose two scheduling schemes for the uplink of LTE-based cellular systems, which take into account both the channel conditions and the maximum allowed delay of each device requesting to be served. In contrast to other scheduling algorithms no classes of devices are formed, but the exact delay constraint of each device is considered, approaching the requirements of M2M communications in a more realistic way. This way, the number of effectively served requests increases, while it becomes possible to exploit the exact delay constraints in order to put the devices in sleep modes, until next transmissions. It is also shown that dividing the devices into a limited number of QoS classes deteriorates the system's performance.
MoS<sub>2</sub>/TiO<sub>2</sub> heterostructures as nonmetal plasmonic photocatalysts for highly efficient hydrogen evolution (2017)

Periodically patterned MoS<sub>2</sub>/TiO<sub>2</sub> heterostructures were rationally designed as nonmetal plasmonic photocatalysts for highly efficient hydrogen evolution.
Structure-Guided Investigation of Lipopolysaccharide O-Antigen Chain Length Regulators Reveals Regions Critical for Modal Length Control (2011)

The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.
Attosecond Synchronization of High-Harmonic Soft X-rays (2003)

Subfemtosecond light pulses can be obtained by superposing several high harmonics of an intense laser pulse. Provided that the harmonics are emitted simultaneously, increasing their number should result in shorter pulses. However, we found that the high harmonics were not synchronized on an attosecond time scale, thus setting a lower limit to the achievable x-ray pulse duration. We showed that the synchronization could be improved considerably by controlling the underlying ultrafast electron dynamics, to provide pulses of 130 attoseconds in duration. We discuss the possibility of achieving even shorter pulses, which would allow us to track fast electron processes in matter.
Percutaneous vertebroplasty guided by a combination of CT and fluoroscopy. (1994)

We describe the technique of percutaneous vertebroplasty using methyl methacrylate. We injected under the guidance of CT and fluoroscopy a group of 10 patients with back pain caused by a variety of vertebral lesions including severe osteoporosis (n = 4), hemangiomas (n = 5) and metastasis (n = 1). Over varying periods of follow-up (ranging from 4 to 17 months) none of the injected vertebral bodies demonstrated compression. All patients had relief of back pain; none had complications related to the technique. We emphasize that the efficacy of this technique in preventing vertebral collapse could not be evaluated in this small sample; a well-controlled study would be required to determine the proper indications and efficacy of this treatment.
Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication (2020)

Therapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.
Introduction to Combinatorial Auctions (2005)

Abstract This book presents an integrated, comprehensive, and interdisciplinary study of combinatorial auctions (CA) in which bids are accepted for packages of items. Applications of CA in various industries including truckload transportation, bus routes, airport takeoff and landing slots, industrial procurement, and the allocation of radio spectrum for wireless communications services. The book starts with a discussion of variety of CA mechanisms including the Vickrey-Clarke-Groves mechanism, iterative combinatorial auctions, simultaneous ascending auctions, and clock-proxy auctions, and also addresses a number of challenges regarding bidding languages and questions of efficiency. Testing of solutions to the winner determination problem that have been proposed is discussed, and an assessment is made of the Combinatorial Auction Test Suite, a software package used for the prediction of the running times of algorithms for the winner determination problem. Further development of this emerging field of CA is expected with the integration of the disciplines of economics, operations research, and computer science.
Additive-Free Chemoselective Acylation of Amines (2009)

Aliphatic and aromatic amines are efficiently acylated by acetic, pivalic, benzoic, phthalic, or maleic anhydrides in ethyl acetate at room temperature. Under the same experimental conditions, amino alcohols are chemoselectively acylated at the amino group.
Sperm binding activity of the zona pellucida of immature mouse oocytes (1986)

Immature oocytes taken from ovarian follicles are sometimes used in studies of sperm-zona interaction in species for which it is difficult to obtain ovulated eggs. As yet, however, there has been no quantitative comparison of the sperm binding capacities of immature and ovulated oocytes. We report here that in mice there is no significant difference in the numbers of sperm which bind to the zonae pellucidae of immature and ovulated oocytes in vitro. These results support the use of immature oocytes in studies of sperm-zona interaction. We have also analyzed the sources of variability in sperm binding assays, and we make suggestions for the most efficient design of experiments.