gebhart/patrepeval huggingface dataset:
Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis (2015)

Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease. The hedgehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however, the role of these effectors during fibrogenesis is poorly understood. Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle progression in cultured mesenchymal stem cell-like progenitors. In animals exposed to unilateral ureteral obstruction, Hh pathway suppression by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limited kidney fibrosis. Myofibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and induction of myofibroblast-specific cell-cycle arrest mediated this inhibition. Pharmacologic targeting of this pathway with darinaparsin, an arsenical in clinical trials, reduced fibrosis through reduction of GLI2 protein levels and subsequent cell-cycle arrest in myofibroblasts. GLI2 overexpression rescued the cell-cycle effect of darinaparsin in vitro. While darinaparsin ameliorated fibrosis in WT and Gli1-KO mice, it was not effective in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin target. The GLI inhibitor GANT61 also reduced fibrosis in mice. Finally, GLI1 and GLI2 were upregulated in the kidneys of patients with high-grade fibrosis. Together, these data indicate that GLI inhibition has potential as a therapeutic strategy to limit myofibroblast proliferation in kidney fibrosis.
Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus (2004)

The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation.
Biochemical Characterization of Trop-2, a Cell Surface Molecule Expressed by Human Carcinomas: Formal Proof that the Monoclonal Antibodies T16 and MOv-16 Recognize Trop-2 (1992)

Trop-2 is a cell surface structure recognized by the 162-46.2 mAb and expressed by most human carcinomas. Since the 162-46.2 mAb works poorly in immunoprecipitation, to characterize the structure of Trop-2 we searched for other mAbs directed against this molecule. Selection of candidates was performed by analyzing the characteristics of mAbs directed against epithelial cells and by comparing the staining pattern of each mAb with the one of the 162-46.2 on frozen sections of human epidermis. Two mAbs, T16 and MOv-16, were selected for further analysis. Formal proof that candidate mAbs reacted with Trop-2 was obtained by comparing their binding patterns to mouse L cells transfected with the Trop-2 gene by genomic DNA transfection and selected by FACS using the FITC-162-46.2 mAb. In immunofluorescence FACS analysis the FITC-T16 and FITC-MOv-16 mAbs specifically stained Trop-2 transfectants. The specificity of binding was confirmed by selective blocking of the staining by the respective unconjugated mAb. Interestingly, cross-blocking studies indicated that the 162-46.2, T16 and MOv-16 mAbs recognize the same epitope or closely spaced ones on the Trop-2 molecule. T16 and MOv-16 efficiently immunoprecipitate Trop-2 from Trop-2 transfectants and from the human cell line OVCA-432, indicating that it is a cell surface glycoprotein, with an apparent molecular weight of 57 kD in non-reducing conditions. A weaker band of 38 kD is often co-precipitated with the 57 kD form in an apparently specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Stability of multi-source droop-controlled Electrical Power System for more-electric aircraft (2014)

The paper deals with the stability of DC Electrical Power System (EPS) with paralleled sources for More Electric Aircraft (MEA). It is known that in presence of tightly controlled power-electronic driven loads the EPS bus capacitances and cable impedances have a significant effect on the system stability boundaries. The paper investigates these boundaries for one of the major paradigms for future MEA EPS that assumes multiple sources feeding into the single main bus. The power sharing between the sources is achieved by implementing droop control. The paper considers possible droop strategies, derives corresponding reduced-order models and applies the impedance criteria to derive EPS stability margins. For the case system considered, the root contours were employed to derive the bus capacitor values to ensure EPS stable operation. The derived stability margins are verified through time-domain simulations.
Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis (2004)

Human neonates infected with herpes simplex virus 1 (HSV-1) develop one of three distinct patterns of infection: (i) infection limited to the skin, eye or mouth; (ii) infection of the CNS; or (iii) disseminated infection. The disseminated form usually involves the liver, adrenal gland, and lung, and resembles the clinical picture of bacterial sepsis. This spectrum of symptoms in HSV-1-infected neonates suggests that inflammatory cytokines play a significant role in the pathogenesis of the disease. Recent studies suggest that the Toll-like receptors (TLRs) may play an important role in the induction of inflammatory cytokines in response to viruses. TLRs are mammalian homologues of Toll, a Drosophila protein that is essential for host defense against infection. Engagement of TLRs by bacterial, viral, or fungal components leads to the production and release of cytokines and other antimicrobial products. Here, we demonstrate that TLR2 mediates the inflammatory cytokine response to HSV-1 by using both transfected cell lines and knockout mice. Studies of infected mice revealed that HSV-1 induced a blunted cytokine response in TLR2(-/-) mice. Brain levels of monocyte chemoattractant protein 1 chemokine were significantly lower in TLR2(-/-) mice than in either wild-type or TLR4(-/-) mice. TLR2(-/-) mice had reduced mortality compared with wild-type mice. The differences between TLR2(-/-) mice and both wild-type and TLR4(-/-) mice in the induction of monocyte chemoattractant protein 1, brain inflammation, or mortality could not be accounted for on the basis of virus levels. Thus, these studies suggest the TLR2-mediated cytokine response to HSV-1 is detrimental to the host.
Two-dimensional position-sensitive photodetector with high linearity made with standard i.c.-technology (1979)

Based on the lateral photoeffect it is possible to construct photodetectors of which the output is dependent on the light-spot position. In the literature, a number of these position-sensitive detectors (p.s.d.) based on the forward or reverse characteristics of a photodiode have been presented. The integration of a p.s.d. with signal processing circuits on one silicon chip may eventually lead to very versatile, high-quality low-cost sensors. Therefore it is necessary to develop a p.s.d. structure which can be fabricated with standard planar silicon technology. In this paper such a novel reverse-biased p.s.d. structure is presented. A 6 × 6 mm2 p.s.d. was made, and an overall linearity better than 0.5% full scale and a photosensitivity of 0.5 A/W for an He-Ne laser were obtained. The dependence of the position sensitivity on background illumination and temperature as well as resolution are similar to those of currently known linear p.s.d.s.
An approach to visual servoing based on coded light (2006)

Positioning a robot with respect to objects by using data provided by a camera is a well known technique called visual servoing. In order to perform a task, the object must exhibit visual features which can be extracted from different points of view. Then, visual servoing is object-dependent as it depends on the object appearance. Therefore, performing the positioning task is not possible in presence of non-textured objects or objects for which extracting visual features is too complex or too costly. This paper proposes a solution to tackle this limitation inherent to the current visual servoing techniques. Our proposal is based on the coded structured light approach as a reliable and fast way to solve the correspondence problem. In this case, a coded light pattern is projected providing robust visual features independently of the object appearance
The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation (2017)

<i>Candida</i><i>auris</i>, a new multidrug-resistant <i>Candida</i> spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 <i>C. auris</i> isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-d-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of <i>C. auris</i> Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of <i>Candida albicans</i> (<i>P</i> = 0.01). <i>C. auris</i> isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC<sub>90</sub> of 1 mg/liter against <i>C. auris</i> and caused complete inhibition of the growth of <i>C. auris</i> and <i>C. albicans</i> Scanning electron microscopy analysis showed that SCY-078 interrupted <i>C. auris</i> cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (<i>P</i> < 0.05 for both comparisons). Our study shows that <i>C. auris</i> expresses several virulence determinants (albeit to a lesser extent than <i>C. albicans</i>) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against <i>C. auris</i>, indicating that further evaluation of this antifungal is warranted.
Characteristics and three-dimensional integration of MOSFET's in small-grain LPCVD polycrystalline Silicon (1985)

Building on nearly two decades of reported results for MOSFET's fabricated in small-grain polycrystalline silicon, a design methodology is developed that yields devices which have low threshold voltage, high drive current, low leakage current, tight parameteric control, and reduced topology, while requiring no nonstandard materials, processes, and tools. Design criteria and device performance are discussed, grain boundary characterization techniques are described, technological issues pertinent to VLSI implementation are investigated, and long-term device reliability is studied. The potential applications of the polysilicon MOSFET's in high-density dRAM and sRAM are explored. The successful implementation of an experimental stacked CMOS 64K static RAM proves the utility of these devices for three-dimensional integration in a VLSI environment.
Distinguishing prostatic from colorectal adenocarcinoma on biopsy samples: the role of morphology and immunohistochemistry. (2007)

P501S is a useful marker in this setting when included together with PSA, CDX2, CK20, and beta-catenin. P501S labels a subset of PCa cases that are negative for PSA. Dirty necrosis and/or columnar cells with basal nuclei could also be of help.
Enantioselective hydrogenation of .beta.-disubstituted .alpha.-acetamidoacrylates catalyzed by rhodium complexes with TRAP trans-chelating chiral phosphine ligands. (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantioselective hydrogenation of .beta.-disubstituted .alpha.-acetamidoacrylates catalyzed by rhodium complexes with TRAP trans-chelating chiral phosphine ligands.Masaya Sawamura, Ryoichi Kuwano, and Yoshihiko ItoCite this: J. Am. Chem. Soc. 1995, 117, 37, 9602–9603Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00142a044https://doi.org/10.1021/ja00142a044research-articleACS PublicationsRequest reuse permissionsArticle Views684Altmetric-Citations96LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
COGNITIVE-EMOTIONAL TRAINING AS AN INTERVENTION FOR MAJOR DEPRESSIVE DISORDER (2014)

Cognitive-emotional training may represent a feasible and effective intervention strategy for MDD. This proof-of-concept study highlights the need for future studies to fully understand the effectiveness, and mechanisms of effect, of these training strategies.
Arousals and aircraft noise - environmental disorders of sleep and health in terms of sleep medicine. (2004)

World wide rules for sleep staging originate to 1967. Since then many investigations aimed to give numbers for the degree of sleep disturbances due to air traffic noise. But the variables used, such as the amount of relative sleep stages, total sleep time, or sleep efficiency, could not explain impairment in health and performance sufficiently. The beginning of the eighties has given new insight into the restorative functions of sleep, according to sleep fragmentation by micro-arousals. These are originating in autonomous dysfunctions during sleep, leading to non-restorative sleep. Environmentally related sleep disturbances are described, EEG and vegetative (micro)-arousals, and the actual knowledge in sleep medicine is given in terms of the international classification of sleep disorders (ICSD). The effects on health, and disturbed performance capacity during the day are shown by self ratings of 160 patients. Elevated metabolic rate caused by micro-arousal and/or insomnia, may play an additional role in health impairment.
Increased forensic efficiency of DNA fingerprints through simultaneous resolution of length and nucleotide variability by high-performance mass spectrometry (2007)

Short tandem repeat (STR) typing is the most powerful method for determining the origin of a sample for a number of molecular disciplines such as medical genetics, population genetics, tumor analysis, transplantation medicine, or forensic crime scene analysis. STR alleles are routinely differentiated based upon their fragment size by electrophoresis under denaturing conditions, which does not take nucleotide variability into consideration. This simplification leads to loss of biological information as the nature of the individual sequence motifs that build an STR is not described. An alternative detection platform would be mass spectrometry, which captures the underlying sequence variation by comparing the molecular masses of DNA fragments. Here, we demonstrate that the combination of ion-pair reversed-phase high-performance liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry (ICEMS) is able to simultaneously detect length and nucleotide variability in STRs. Overall, 21 forensically relevant STRs that are also used in other scientific fields were screened in an Austrian population sample for the occurrence of nucleotide variability within or close to the repeat region. A total of 11 of the investigated loci (SE33, D2S1338, vWA, D21S11, D3S1358, D16S539, D8S1179, D7S820, D13S317, D5S818, and D2S441) brought additional allele (sequence) variants. Forensic efficiency, as determined by typical statistical parameters, was significantly increased by 20 to 30%. The beauty of ICEMS-STR-analysis is the fact that it represents one of the few technological advancements that allows direct comparison of newly generated data with existing data such as stored in DNA databases, which have a retarding effect on new developments.
Evidence for an Autocrine Role of Activin B within Rat Anterior Pituitary Cultures (1991)

Activins, dimers of inhibin beta subunits, are potent stimulators of FSH secretion in vivo and in vitro and of FSH beta mRNA expression in rat anterior pituitary cultures. In this study, we investigated the possibility that locally secreted activin B (beta B beta B) may function as an autocrine modulator of basal FSH secretion and expression based on the previous observation that beta B is expressed within gonadotropes. The incubation of cultured rat anterior pituitary cells with a m mouse monoclonal antibody specific for the activin B homodimer (MAb-activin B) significantly attenuated the basal secretion of FSH in a concentration- and time-dependent manner, without influencing LH secretion. Moreover, MAb-activin B selectively inhibited FSH beta mRNA accumulation without affecting either LH beta or alpha subunit mRNAs. The MAb-activin B completely blocked the stimulation of FSH secretion by exogenous activin B, but not by activin A, confirming its specificity. As previously shown, inhibin A and follistatin significantly suppressed basal FSH secretion in these cultures. This inhibitory effect, albeit of lower magnitude, was still evident even in the presence of the MAb-activin B which by itself suppressed basal FSH secretion. These data suggest that the secretion of activin B by the gonadotropes of the anterior pituitary may serve as an autocrine signal in the selective modulation of FSH expression and secretion. Furthermore, the inhibitory actions of inhibins and follistatins on gonadotropes may, in part, be explained by their ability to interfere with the actions of endogenous activin B.
Quantitative miRNA expression analysis: Comparing microarrays with next-generation sequencing (2009)

Recently, next-generation sequencing has been introduced as a promising, new platform for assessing the copy number of transcripts, while the existing microarray technology is considered less reliable for absolute, quantitative expression measurements. Nonetheless, so far, results from the two technologies have only been compared based on biological data, leading to the conclusion that, although they are somewhat correlated, expression values differ significantly. Here, we use synthetic RNA samples, resembling human microRNA samples, to find that microarray expression measures actually correlate better with sample RNA content than expression measures obtained from sequencing data. In addition, microarrays appear highly sensitive and perform equivalently to next-generation sequencing in terms of reproducibility and relative ratio quantification.
Nutraceutical Approach for Preventing Obesity-Related Colorectal and Liver Carcinogenesis (2012)

Obesity and its related metabolic abnormalities, including insulin resistance, alterations in the insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) axis, and the state of chronic inflammation, increase the risk of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, these findings also indicate that the metabolic disorders caused by obesity might be effective targets to prevent the development of CRC and HCC in obese individuals. Green tea catechins (GTCs) possess anticancer and chemopreventive properties against cancer in various organs, including the colorectum and liver. GTCs have also been known to exert anti-obesity, antidiabetic, and anti-inflammatory effects, indicating that GTCs might be useful for the prevention of obesity-associated colorectal and liver carcinogenesis. Further, branched-chain amino acids (BCAA), which improve protein malnutrition and prevent progressive hepatic failure in patients with chronic liver diseases, might be also effective for the suppression of obesity-related carcinogenesis because oral supplementation with BCAA reduces the risk of HCC in obese cirrhotic patients. BCAA shows these beneficial effects because they can improve insulin resistance. Here, we review the detailed relationship between metabolic abnormalities and the development of CRC and HCC. We also review evidence, especially that based on our basic and clinical research using GTCs and BCAA, which indicates that targeting metabolic abnormalities by either pharmaceutical or nutritional intervention may be an effective strategy to prevent the development of CRC and HCC in obese individuals.