gebhart/patrepeval huggingface dataset:
Differential Gene Up-Regulation by Hypoxia-Inducible Factor-1α and Hypoxia-Inducible Factor-2α in HEK293T Cells (2005)

Cells exposed to hypoxia respond by increasing the level of hypoxia-inducible factor-1 (HIF-1). This factor then activates a number of genes by binding to hypoxia response elements in their promoter regions. A second hypoxia-responsive factor, HIF-2, can activate many of the same genes as HIF-1. Overexpression of HIFs accompanies the pathogenesis of many tumors. It is unclear, however, as to the respective role of these factors in responsiveness to hypoxia and other stresses. To address this issue, we used microarray technology to study the genes activated in HEK293T cells by hypoxia or transfection with the alpha chain of HIF-1 (or mutant HIF-1 resistant to degradation) or HIF-2. Fifty-six genes were found to be up-regulated at least 3-fold by either hypoxia or transfection. Of these, 21 were elevated both by transfection with HIF-1alpha and with HIF-2alpha, and 14 were preferentially activated by HIF-1alpha including several involved in glycolysis. Ten genes were preferentially activated by HIF-2alpha, including two (CACNA1A and PTPRZ1) implicated in neurologic diseases. Interestingly, most HIF-2alpha-responsive genes were not substantially activated by hypoxia. An additional 10 genes were up-regulated by hypoxia but minimally activated by HIF-1alpha or HIF-2alpha transfection. Ten of the genes were studied by quantitative real-time PCR and/or by Northern blot and the results paralleled those found with microarray technology. Although confirmation in other systems will be necessary, these results indicate that whereas some genes are robustly activated by both HIF-1 and HIF-2, others can be preferentially activated by one or the other factor.
Deregulation of Rab and Rab Effector Genes in Bladder Cancer (2012)

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer.
Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis (2003)

Inflammation underlies both onset and perpetuation of atherosclerosis. Plasma lipoproteins transport the platelet-activating factor-acetylhydrolase (PAF-AH) with potentially anti-inflammatory activities. Our aim was to determine whether PAF-AH activity was associated with inflammatory markers and with coronary artery disease (CAD). PAF-AH activity and a panel of inflammatory mediators were measured in plasma of 496 patients with CAD and in 477 controls; 276 patients presented with stable angina pectoris and 220 with acute coronary syndrome (ACS). Individuals within the highest quartile of PAF-AH activity had an 1.8-fold increase in CAD risk [95% confidence interval (CI), 1.01 to 3.2; P = 0.048] compared with those in the first quartile (adjusted for clinical and metabolic factors). When excluding individuals receiving statin and angiotensin-converting enzyme-inhibitor medication, individuals within the highest quartile of PAF-AH activity revealed a 3.9-fold increase in CAD risk (95% CI, 2.0 to 7.7; P < 0.0001). In these subjects, the plasma PAF-AH activity increased gradually in stable angina and in ACS both in men (P < 0.0001) and in women (P < 0.001), as compared with controls. No correlation was found between PAF-AH levels and those of common markers of inflammation. This study and the previous ones raise the important issue of whether PAF-AH is simply a marker of risk or directly promotes atherosclerosis.
Near optimal energy selective x‐ray imaging system performance with simple detectors (2010)

Low energy resolution detectors can be used in energy selective x-ray imaging systems to produce images with near optimal performance.
Purification of cholesterol 7 alpha-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies. (1990)

Cholesterol 7 alpha-hydroxylase, the cytochrome P-450-dependent and rate-controlling enzyme of bile acid synthesis, was purified from rat and human liver microsomes. The purified fractions were assayed in a reconstituted system containing [4-14C]cholesterol, and cholesterol 7 alpha-hydroxylase activities in these fractions increased 500-600-fold relative to whole microsomes. Polyacrylamide gel electrophoresis of rat microsomes followed by immunoblotting with polyclonal rabbit antisera raised against purified cholesterol 7 alpha-hydroxylases revealed two peaks at molecular masses of 47,000 and 49,000 daltons for both rat and human fractions. Increasing amounts of rabbit anti-rat and anti-human antibodies progressively inhibited rat microsomal cholesterol 7 alpha-hydroxylase activity up to 80%. In contrast, monospecific antibodies raised against other purified cytochrome P-450 enzymes (P-450f, P-450g, and P-450j) did not inhibit rat or human cholesterol 7 alpha-hydroxylase activity. Immunoblots of rat microsomes with the rabbit anti-rat cholesterol 7 alpha-hydroxylase antibody demonstrated that the antibody reacted quantitatively with the rat microsomal enzyme. Microsomes from cholesterol-fed rats showed increased cholesterol 7 alpha-hydroxylase mass, whereas treatment with pravastatin, an inhibitor of hydroxy-methylglutaryl-coenzyme A reductase, reduced enzyme mass. Microsomes from starved rats contained slightly less cholesterol 7 alpha-hydroxylase protein than chow-fed control rats. These results indicate a similarity in molecular mass, structure, and antigenicity between rat and human cholesterol 7 alpha-hydroxylases; demonstrate the production of inhibiting anti-cholesterol 7 alpha-hydroxylase antibodies that can be used to measure the change in cholesterol 7 alpha-hydroxylase enzyme mass under various conditions; and emphasize the unique structure of cholesterol 7 alpha-hydroxylase with respect to other cytochrome P-450-dependent hydroxylases.
New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19 (2020)

Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families, including <i>Coronaviridae</i> Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir leads to improved survival, decreased lung injury, and decreased levels of viral RNA. Recent clinical data have demonstrated the clinical activity of remdesivir in terms of faster time to recovery in patients with severe COVID-19 and higher odds of improved clinical status in patients with moderate COVID-19. Here, clinical trials published to date are presented and appraised. Remdesivir's potential benefits and its favorable adverse-event profile make it an option for the treatment of COVID-19. This article examines the available literature describing remdesivir's pharmacology, pharmacokinetics, and preclinical and clinical data.
A Fabry-Perot microinterferometer for visible wavelengths (2003)

The authors report on their efforts to develop a silicon-based microinterferometer for optical applications in the visible spectral region using micromachining fabrication techniques. The interferometer is formed by two parallel dielectric mirrors supported on membranes which are electrostatically deflected for wavelength control. A simplified two-wafer fabrication process was designed and investigated. They obtained 250 nm membrane deflection for an applied voltage of 100 V. Hafnium dioxide-silicon dioxide dielectric mirrors with high reflectivity and low stress were fabricated on membrane supports and also free-standing. Anticipated applications include microinstrument spectroscopy systems for atomic absorption, ellipsometry, imaging, optical fiber communications, and general spectrophotometer uses as well as accelerometry.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance (2017)

Peripheral T cell tolerance is promoted by the regulatory cytokine TGF-β and Foxp3-expressing Treg cells. However, whether TGF-β and Treg cells are part of the same regulatory module, or exist largely as distinct pathways to repress self-reactive T cells remains incompletely understood. Using a transgenic model of autoimmune diabetes, here we show that ablation of TGF-β receptor II (TβRII) in T cells, but not Foxp3 deficiency, resulted in early-onset diabetes with complete penetrance. The rampant autoimmune disease was associated with enhanced T cell priming and elevated T cell expression of the inflammatory cytokine GM-CSF, concomitant with pancreatic infiltration of inflammatory monocytes that triggered immunopathology. Ablation of the GM-CSF receptor alleviated the monocyte response and inhibited disease development. These findings reveal that TGF-β promotes T cell tolerance primarily via Foxp3-independent mechanisms and prevents autoimmunity in this model by repressing the cross talk between adaptive and innate immune systems.
A fully integrated transformer-based front-end architecture for wireless transceivers (2005)

A fully integrated transformer-based RF front-end architecture is presented that integrates matching, combining, and T/R switch functions on chip. The front-end is implemented in a 0.18 /spl mu/m CMOS Bluetooth transceiver achieving -90dBm receiver sensitivity and 2dBm transmit power from a 1.8V supply.
Prandial insulin: is inhaled enough? (2008)

Abstract The low proportion of patients achieving glycemic targets is well documented for both type 1 and type 2 diabetes. Postprandial glucose levels are often not monitored but contribute significantly to total glycemic burden. Prandial rapid‐acting insulin analogues were introduced to address some of these problems but still do not provide a physiologic insulin replacement. Inhaled prandial insulins have been developed to free patients from multiple mealtime injections and make intensive insulin regimens more acceptable. Several inhaled formulations of prandial insulin are in development but differ significantly with respect to inhaler characteristics and pharmacokinetic profiles. This brief review summarizes the properties of the new prandial inhaled insulins and discusses how postprandial glycemic control is dependent not only on the insulin dose, but also on the pharmacokinetic characteristics of insulin delivery. There is no antihyperglycemic agent with a glucose‐lowering effect superior to that of insulin; new prandial products that improve coordination between insulin availability and meal absorption and are more acceptable to patients may increase the proportion of diabetic patients achieving and maintaining glycemic targets. Drug Dev Res 69:138–142, 2008. © 2008 Wiley‐Liss, Inc.
Activation of dense human tonsilar B cells. Induction of c-myc gene expression via two distinct signal transduction pathways (1991)

Antibodies to surface Ig or to the B cell marker CD20 trigger resting human B cells in similar yet distinct ways. Either antibody induces five-fold increases in the expression of the protooncogene, c-myc, as detected with semi-quantitative Northern blot assays. The induction of c-myc mRNA by anti-IgM or anti-CD20 is blocked by inhibitors of protein kinase C (PKC) such as staurosporine and by pretreatment of B cells with phorbol esters to reduce cellular PKC levels. This suggests that PKC is involved in the pathways stimulated by both anti-IgM and anti-CD20. However, anti-CD20, unlike anti-IgM, does not activate significant increases in inositol triphosphate or intracellular-free calcium. Further, anti-CD20-triggered elevation of c-myc mRNA is inhibited by pertussis and cholera toxins, whereas the pathway initiated by anti-IgM if anything is stimulated by pertussis toxin and unchanged by cholera toxin. Further differences in the nature of these two signals were seen when the expression of adhesion/recognition molecules were examined. Anti-IgM consistently induces increased expression of the adhesion molecules CD54 (I-CAM-1) and B7/BB-1 on B cells, but anti-CD20 does not. Yet both anti-CD20 and anti-IgM increase class II MHC, CD18 (LFA-1 beta-chain) and LFA-3 levels. These data suggest that the way in which B cells are activated may influence their surface phenotype and possibly subsequent migration or cell-cell interactions.
A Virtualized Separation Kernel for Mixed-Criticality Systems (2016)

Multi- and many-core processors are becoming increasingly popular in embedded systems. Many of these processors now feature hardware virtualization capabilities, as found on the ARM Cortex A15 and x86 architectures with Intel VT-x or AMD-V support. Hardware virtualization provides a way to partition physical resources, including processor cores, memory, and I/O devices, among guest virtual machines (VMs). Each VM is then able to host tasks of a specific criticality level, as part of a mixed-criticality system with different timing and safety requirements. However, traditional virtual machine systems are inappropriate for mixed-criticality computing. They use hypervisors to schedule separate VMs on physical processor cores. The costs of trapping into hypervisors to multiplex and manage machine physical resources on behalf of separate guests are too expensive for many time-critical tasks. Additionally, traditional hypervisors have memory footprints that are often too large for many embedded computing systems. In this article, we discuss the design of the Quest-V separation kernel, which partitions services of different criticality levels across separate VMs, or sandboxes . Each sandbox encapsulates a subset of machine physical resources that it manages without requiring intervention from a hypervisor. In Quest-V, a hypervisor is only needed to bootstrap the system, recover from certain faults, and establish communication channels between sandboxes. This not only reduces the memory footprint of the most privileged protection domain but also removes it from the control path during normal system operation, thereby heightening security.
CD39 Is an Ecto-(Ca2+,Mg2+)-apyrase (1996)

CD39, a 70- to 100-kDa molecule expressed primarily on activated lymphoid cells, was previously identified as a surface marker of Epstein Barr virus (EBV)-transformed B cells. In this report, we show that an ecto-(Ca2+,Mg2+)-apyrase activity is present on EBV-transformed B cells, but not on B or T lymphomas. The coincidence between CD39 expression and ecto-apyrase activity on immune cells suggests that CD39 may be an ecto-apyrase. This supposition is supported by the observation that the amino acid sequence of CD39 is significantly homologous to those of several newly identified nucleotide triphosphatases. Finally, we show that CD39 indeed has ecto-apyrase activity by expression in COS-7 cells.
Proliferation-dependent HIV-1 infection of monocytes occurs during differentiation into macrophages. (1992)

Requirements for the establishment of productive infection with the human immunodeficiency virus type 1 (HIV-1) in primary monocytes were investigated. In vitro, monocytes rendered susceptible for infection after at least a 2-d culture, but when cultured in the presence of differentiation-inducing agent IL-4, accelerated susceptibility was seen. Complete resistance to HIV-1 infection was observed in monocytes that had been treated for 5 d with rIL-4, and comparable results were obtained with other differentiation inducers such as dexamethasone or 1,25(OH)2 vitamin D3 (1,25(OH)2vitD3). The inhibition of productive infection was not caused by downregulation of CD4 expression or HIV-1 transcription, nor by intracellular accumulation of virions. Since treatment with rIL-4, dexamethasone, or 1,25(OH)2vitD3 also resulted in complete inhibition of monocyte proliferation, we studied whether establishment of productive infection in monocytes is proliferation dependent. Irradiation or mitomycin-C treatment within 24 h after inoculation prevented productive HIV-1 infection of monocytes, suggesting a proliferation-dependent step early in the virus replication cycle. Polymerase chain reaction (PCR) analysis revealed the presence of only incomplete proviral DNA species in non-proliferating monocytes, indicating restriction of viral replication at the level of reverse transcription. Thus, in analogy with HIV-1 infection of CD4+ T cells, proliferation of monocytes during differentiation into macrophages is a prerequisite for productive infection with HIV.
Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer (2002)

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. However, reliable diagnostic or prognostic tumor markers have not been identified for endometrial cancer. In this study, we examined whether urokinase plasminogen activator receptor (UPAR), a glycosyl-phosphatidylinositol-linked membrane protein, is a candidate diagnostic or prognostic marker for patients with cancer of the endometrium. Sixty-five surgically excised, formalin-fixed endometrial tissue specimens were accessioned through the Department of Pathology Registry at the University of California, Los Angeles, and analyzed for UPAR expression by using immunohistochemical techniques. A retrospective review was also performed to determine stage and histopathologic grade of disease, recurrence, and mortality. No expression of UPAR protein was present in seven patients with benign neoplasia of the endometrium. UPAR protein expression highly correlated with stage of disease (ungrouped Spearman correlation = 0.625, P < 0.0001): 40% of patients with stage I, 66% of patients with stage II, 100% of patients with stage III, and 85% with stage IV demonstrated the highest level of UPAR expression. Moreover, high UPAR expression positively correlated with grade of disease (ungrouped Spearman correlation = 0.71, P < 0.0001): 29% of grade 1 specimens, 57% of grade 2, and over 90% of specimens with grade 3, the majority representing uterine papillary serous carcinoma and mixed malignant mesodermal tumor. Finally, UPAR protein expression also positively correlated with rate of recurrence and mortality in patients with adenocarcinoma of the endometrium (ungrouped P = 0.034). Our data suggest that UPAR is a useful prognostic marker for biologically aggressive forms of endometrial cancer.
Blood Pressure and the Risk of Cardiovascular Disease (2000)

The level of blood pressure has long been recognized as a determinant of the risks for several common cardiovascular diseases, including coronary heart disease, cerebrovascular disease, and heart failure. Throughout the 20th century, most attention has focused on the risks of these diseases (and the possibility of their reversal) among persons considered to have hypertension. However, there are several important reasons to question the appropriateness of continuing to focus attention primarily on hypertension and its treatment, as opposed to the broader concept of blood-pressure–related disease and its prevention. Some of these reasons are illustrated in the report by van den . . .
Optical Barker codes (1974)

Certain binary codes having good autocorrelation properties akin to Barker codes are studied.
Fundamentals of Probability and Statistics for Engineers (2004)

This textbook differs from others in the field in that it has been prepared very much with students and their needs in mind, having been classroom tested over many years. It is a true "learner's book" made for students who require a deeper understanding of probability and statistics. It presents the fundamentals of the subject along with concepts of probabilistic modelling, and the process of model selection, verification and analysis. Furthermore, the inclusion of more than 100 examples and 200 exercises (carefully selected from a wide range of topics), along with a solutions manual for ins
The arcelin-5 Gene of Phaseolus vulgarisDirects High Seed-Specific Expression in TransgenicPhaseolus acutifolius and Arabidopsis Plants1 (1999)

The regulatory sequences of many genes encoding seed storage proteins have been used to drive seed-specific expression of a variety of proteins in transgenic plants. Because the levels at which these transgene-derived proteins accumulate are generally quite low, we investigated the utility of the arcelin-5 regulatory sequences in obtaining high seed-specific expression in transgenic plants. Arcelin-5 is an abundant seed protein found in some wild common bean (Phaseolus vulgaris L.) genotypes. Seeds of Arabidopsis and Tepary bean (Phaseolus acutifolius A. Gray) plants transformed with arcelin-5 gene constructs synthesized arcelin-5 to levels of 15% and 25% of the total protein content, respectively. To our knowledge, such high expression levels directed by a transgene have not been reported before. The transgenic plants also showed low plant-to-plant variation in arcelin expression. Complex transgene integration patterns, which often result in gene silencing effects, were not associated with reduced arcelin-5 expression. High transgene expression was the result of high mRNA steady-state levels and was restricted to seeds. This indicates that all requirements for high seed-specific expression are cis elements present in the cloned genomic arcelin-5 sequence and trans-acting factors that are available in Arabidopsis and Phaseolus spp., and thus probably in most dicotyledonous plants.