gebhart/patrepeval huggingface dataset:
Vertical Sleeve Gastrectomy Improves Glucose and Lipid Metabolism and Delays Diabetes Onset in UCD-T2DM Rats (2012)

Vertical sleeve gastrectomy (VSG) has gained interest as a low morbidity bariatric surgery, which is effective in producing weight loss and causing type 2 diabetes resolution. However, the efficacy of VSG to prevent the onset of type 2 diabetes has not been previously investigated. VSG or sham surgery was performed on 2-month-old prediabetic male University of California Davis-type 2 diabetes mellitus rats. Sham-operated animals were either sham-operated ad libitum fed (S-AL) or were weight-matched to VSG-operated animals (S-WM). Diabetes onset was determined by weekly nonfasting blood glucose measurements. Animals underwent oral glucose tolerance tests at 1 and 4 months after surgery and indirect calorimetry at 1.5 months after surgery. VSG surgery significantly delayed diabetes onset compared with both S-AL and S-WM animals. VSG-operated animals ate 23% less and weighed 20% less than S-AL. Energy expenditure did not differ between VSG-operated animals and controls. Results from the oral glucose tolerance tests demonstrate improved glucose tolerance and islet function in VSG-operated animals compared with S-AL and S-WM. Nutrient-stimulated glucagon-like peptide (GLP)-1, GLP-2, and peptide YY excursions were greater in VSG-operated animals. VSG surgery resulted in decreased fasting plasma insulin, ghrelin and lipid concentrations, and markedly higher fasting plasma adiponectin and bile acid concentrations, independent of body weight. Increases of circulating bile acid concentrations were due to selective increases of taurine-conjugated bile acids. Thus, VSG delays type 2 diabetes onset in the University of California Davis-type 2 diabetes mellitus rat, independent of body weight. This is potentially mediated by increases of circulating bile acids, adiponectin, and nutrient-stimulated GLP-1 secretion and decreased circulating ghrelin concentrations.
Identification of a microRNA signature of renal ischemia reperfusion injury (2010)

Renal ischemia reperfusion injury (IRI) is associated with significant morbidity and mortality. Given the importance of microRNAs (miRNAs) in regulating gene expression, we examined expression profiles of miRNAs following renal IRI. Global miRNA expression profiling on samples prepared from the kidneys of C57BL/6 mice that underwent unilateral warm ischemia revealed nine miRNAs (miR-21, miR-20a, miR-146a, miR-199a-3p, miR-214, miR-192, miR-187, miR-805, and miR-194) that are differentially expressed following IRI when compared with sham controls. These miRNAs were also differently expressed following IRI in immunodeficient RAG-2/common gamma-chain double-knockout mice, suggesting that the changes in expression observed are not significantly influenced by lymphocyte infiltration and therefore define a lymphocyte-independent signature of renal IRI. In vitro studies revealed that miR-21 is expressed in proliferating tubular epithelial cells (TEC) and up-regulated by both cell-intrinsic and -extrinsic mechanisms resulting from ischemia and TGF-beta signaling, respectively. In vitro, knockdown of miR-21 in TEC resulted in increased cell death, whereas overexpression prevented cell death. However, overexpression of miR-21 alone was not sufficient to prevent TEC death following ischemia. Our findings therefore define a molecular fingerprint of renal injury and suggest miR-21 may play a role in protecting TEC from death.
Finite-Memory Universal Prediction of Individual Sequences (2004)

The problem of predicting the next outcome of an individual binary sequence under the constraint that the universal predictor has a finite memory, is explored. In this analysis, the finite-memory universal predictors are either deterministic or random time-invariant finite-state (FS) machines with K states (K-state machines). The paper provides bounds on the asymptotic achievable regret of these constrained universal predictors as a function of K, the number of their states, for long enough sequences. The specific results are as follows. When the universal predictors are deterministic machines, the comparison class consists of constant predictors, and prediction is with respect to the 0-1 loss function (Hamming distance), we get tight bounds indicating that the optimal asymptotic regret is 1/(2K). In that case of K-state deterministic universal predictors, the constant predictors comparison class, but prediction is with respect to the self-information (code length) and the square-error loss functions, we show an upper bound on the regret (coding redundancy) of O(K/sup -2/3/) and a lower bound of /spl Theta/(K/sup -4/5/). For these loss functions, if the predictor is allowed to be a random K-state machine, i.e., a machine with random state transitions, we get a lower bound of /spl Theta/(1/K) on the regret, with a matching upper bound of O(1/K) for the square-error loss, and an upper bound of O(logK/K) Throughout the paper for the self-information loss. In addition, we provide results for all these loss functions in the case where the comparison class consists of all predictors that are order-L Markov machines.
Lipid membrane phase behaviour elucidated in real time by controlled environment atomic force microscopy (2002)

Lipids are integral components of all biological membranes. Understanding the physical and chemical properties of these lipids is critical to our understanding of membrane functions. We developed a new atomic force microscope (AFM) approach to visualize in real time the temperature-induced lipid phase transition and domain separation processes in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes and estimate the thermodynamics of the phase transition process. The gel and liquid crystalline phases of DMPC coexisted over a broad temperature range (approximately 10 degrees C). Equal partitioning into two phases occurred at a transition temperature (Tm) of 28.5 degrees C. We developed a mathematical model to analyse AFM-derived DMPC membrane height changes as multi-peak Gaussian distributions. This approach allowed us to estimate the DMPC domain size, N, as 18-75 molecules per leaflet corresponding to a -4.2 nm diameter circular nanodomain. Lipid nanodomains may organize into microdomains or rafts which, in concert with proteins and other lipid components, play an important dynamic role in many biomedically important processes.
Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma (2014)

Regions of AFMM contain hypercellularity except for regions with extremely restricted diffusion, where necrosis is present.
Gastrin and Glycine-extended Progastrin Processing Intermediates Induce Different Programs of Early Gene Activation (1995)

We recently reported that gastrin and glycine-extended progastrin processing intermediates (G-Gly) exert growth-promoting effects on AR4-2J cells (derived from rat pancreas) via interaction with distinct receptors. In this study we sought to investigate the mechanisms by which gastrin and G-Gly stimulate cell proliferation. While gastrin increased [Ca2+]i in AR4-2J cells, G-Gly had no effect. Similarly, G-Gly had no effect either on basal and 10(-7) M vasoactive intestinal polypeptide-stimulated cAMP generation, although gastrin is known to inhibit cAMP generation. Gastrin dose dependently stimulated AR4-2J cell mRNA content of both c-fos and c-jun, two genes known to function in regulating cell proliferation, but G-Gly had no effect. Gastrin also induced the expression of luciferase in AR4-2J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element of the c-fos gene promoter. In similar fashion, gastrin stimulated the activity of mitogen-activated protein kinase, an enzyme known to mediate the induction of the c-fos serum response element in response to growth factor stimulation. Although G-Gly had none of these effects of gastrin in AR4-2J cells, it stimulated activity of c-Jun amino-terminal kinase, an enzyme known to phosphorylate and transcriptionally activate c-Jun. These data support the notion that gastrin stimulates cell proliferation by inducing c-fos and c-jun gene expression, while G-Gly acts by post-translationally regulating early gene transcriptional activation. Our studies represent a novel model in which both the precursor and the product of a key processing reaction, peptide alpha-amidation, act cooperatively to stimulate cell proliferation via distinct receptors linked to different signal transduction pathways.
Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy. (2015)

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m 2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m 2 over 24 h) plus racemic leucovorin (LV) (200 mg/m 2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m 2 IV over 90 min) prior to 5FU (2,400 mg/m 2 over 46 h) and racemic LV (400 mg/m 2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]
Accretion And Star Formation In Rqqs (2016)

Active Galactic Nuclei (AGN) and star-forming galaxies are well-traced in the radio part of the electromagnetic spectrum, due to emission at these wavelengths being unaffected by dust obscuration. The key processes involved in producing the radio emission are black-hole accretion and star formation, both of which are thought to be crucial in determining how galaxies evolve. Disentangling the two contributions requires multi-wavelength data, and this is the approach we use for our work on radio-quiet quasars (RQQs). In contrast to previous studies, we find that accretion-connected radio emission dominates over that due to star formation, even at very low radio flux-densities. The first sample we describe is selected from the VISTA Deep Extragalactic Observations (VIDEO) survey, whose depth allows the study of very low accretion rates and/or lower-mass black holes. A second sample is obtained from the Spitzer-Herschel Active Galaxy Survey, spanning a factor of ~100 in optical luminosity over a narrow redshift range at z ~ 1. This enables evolutionary effects to be decoupled when comparisons are made with the VIDEO sample. Using radio data from the Karl G. Jansky Very Large Array (JVLA), we find further support that the AGN makes a significant contribution to the radio emission in RQQs. In addition, the levels of accretion and star formation appear to be weakly correlated with each other, and with optical luminosity.
Clinical assessment of drug–drug interactions of tasimelteon, a novel dual melatonin receptor agonist (2015)

Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans. Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin pretreatment resulted in a decrease in tasimelteon's exposure of approximately 89%.
Variability in expression of cell surface antigens of Candida albicans during morphogenesis (1986)

The location and expression of two different cell surface antigens on germinating and nongerminating Candida albicans cells was examined by using transmission electron microscopy after labeling with monoclonal antibodies (H9 or C6) and immunocolloidal gold. Immunodeterminant expression of the two carbohydrate antigens was followed from early germination events through 20 h of development. The determinant detected by H9 antibody, which was initially lost from the mother cell surface and preferentially expressed only on hyphae during the first 4 h of germination, reappeared on the mother cell by 20 h, whereas the antigen detected by antibody C6 was continually expressed on mother cells and germ tubes throughout germination.
Hyaluronic Acid, Meniscal Debridement Deemed Worthless in Reviews (2014)

Separate newly published assessments describe hyaluronic acid injections and debridement after meniscectomy of scant clinical value for longstanding relief of knee pain, whatever small statistical significance may turn up in some studies.
Main-memory hash joins on multi-core CPUs: Tuning to the underlying hardware (2013)

The architectural changes introduced with multi-core CPUs have triggered a redesign of main-memory join algorithms. In the last few years, two diverging views have appeared. One approach advocates careful tailoring of the algorithm to the architectural parameters (cache sizes, TLB, and memory bandwidth). The other approach argues that modern hardware is good enough at hiding cache and TLB miss latencies and, consequently, the careful tailoring can be omitted without sacrificing performance. In this paper we demonstrate through experimental analysis of different algorithms and architectures that hardware still matters. Join algorithms that are hardware conscious perform better than hardware-oblivious approaches. The analysis and comparisons in the paper show that many of the claims regarding the behavior of join algorithms that have appeared in literature are due to selection effects (relative table sizes, tuple sizes, the underlying architecture, using sorted data, etc.) and are not supported by experiments run under different parameters settings. Through the analysis, we shed light on how modern hardware affects the implementation of data operators and provide the fastest implementation of radix join to date, reaching close to 200 million tuples per second.
mago nashi mediates the posterior follicle cell-to-oocyte signal to organize axis formation in Drosophila (1997)

Establishment of the anteroposterior and dorsoventral axes in the Drosophila egg chamber requires reciprocal signaling between the germ line and soma. Upon activation of the Drosophila EGF receptor in the posterior follicle cells, these cells signal back to the oocyte, resulting in a reorganization of the oocyte cytoplasm and anterodorsal migration of the oocyte nucleus. We demonstrate that the gene mago nashi (mago) encodes an evolutionarily conserved protein that must be localized within the posterior pole plasm for germ-plasm assembly and Caenorhabditis elegans mago is a functional homologue of Drosophila mago. In the absence of mago+ function during oogenesis, the anteroposterior and dorsoventral coordinates of the oocyte are not specified and the germ plasm fails to assemble.
Therapeutic Window of MuS110, a Single-Chain Antibody Construct Bispecific for Murine EpCAM and Murine CD3 (2008)

EpCAM (CD326) is one of the most frequently and highly expressed tumor-associated antigens known and recently has also been found on cancer stem cells derived from human breast, colon, prostate, and pancreas tumors. However, like many other tumor-associated antigens used for antibody-based immunotherapeutic approaches, EpCAM is expressed on normal tissues including epithelia of pancreas, colon, lung, bile ducts, and breast. To assess the therapeutic window of an EpCAM/CD3-bispecific single-chain antibody construct of the bispecific T-cell engager (BiTE) class, we constructed murine surrogate of MT110 (muS110) from single-chain antibodies specific for murine EpCAM and CD3 antigens. Immunhistochemical analysis showed that, with minor differences, the expression of EpCAM protein on a large variety of tissues from man and mouse was similar with respect to distribution and level. MuS110 exhibited significant antitumor activity at as low as 5 microg/kg in both syngeneic 4T1 orthotopic breast cancer and CT-26 lung cancer mouse models. Dosing of muS110 for several weeks up to 400 microg/kg by intraanimal dose escalation was still tolerated, indicating existence of a significant therapeutic window for an EpCAM-specific BiTE antibody in mice. MuS110 was found to have similar in vitro characteristics and in vivo antitumor activity as MT110, a human EpCAM/human CD3-bispecific BiTE antibody that currently is in formal preclinical development.
Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection (2007)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a threat to human health worldwide. Although progress has been made, mechanisms of CA-MRSA pathogenesis are poorly understood and a comprehensive analysis of CA-MRSA exoproteins has not been conducted. To address that deficiency, we used proteomics to identify exoproteins made by MW2 (USA400) and LAC (USA300) during growth in vitro. Two hundred and fifty unique exoproteins were identified by 2-dimensional gel electrophoresis coupled with automated direct infusion-tandem mass spectrometry (ADI-MS/MS) analysis. Eleven known virulence-related exoproteins differed in abundance between the strains, including alpha-haemolysin (Hla), collagen adhesin (Cna), staphylokinase (Sak), coagulase (Coa), lipase (Lip), enterotoxin C3 (Sec3), enterotoxin Q (Seq), V8 protease (SspA) and cysteine protease (SspB). Mice infected with MW2 or LAC produced antibodies specific for known or putative virulence factors, such as autolysin (Atl), Cna, Ear, ferritin (Ftn), Lip, 1-phosphatidylinositol phosphodiesterase (Plc), Sak, Sec3 and SspB, indicating the exoproteins are made during infection in vivo. We used confocal microscopy to demonstrate aureolysin (Aur), Hla, SspA and SspB are produced following phagocytosis by human neutrophils, thereby linking exoprotein production in vitro with that during host-pathogen interaction. We conclude that the exoproteins identified herein likely account in part for the success of CA-MRSA as a human pathogen.
Noninvasive, real-time monitoring of renal function: the ambulatory renal monitor. (1993)

The objective of this study was to develop a method for the noninvasive, continuous and real-time monitoring of renal function. A radiation detector attached to a miniature data logger was used to monitor the clearance of the glomerular filtration agent 99mTc-diethylenetriaminepentaacetic acid from the extracellular space. The rate constant (k) for this clearance showed an excellent correlation with simultaneous glomerular filtration rate (GFR) measurements performed with a standard 125I-iothalamate clearance technique in 50 patients. Moreover, the reproducibility of the k measurement for an individual or a population was superior to the GFR measurement performed with the standard clearance technique. The procedure was also used to monitor the renal function in patients at risk for acute renal failure during angiography or in the intensive care unit under noninvasive and near real-time conditions. The results show that the technique detects rapid changes in renal function with a resolution time of 5 min in patients with normal renal function and 15 min in patients with severely impaired renal function. Since the method is noninvasive, precise and provides a near real-time measurement of GFR, its use may lead to an improvement in the management of patients in situations in which a rapid measurement is the major concern.
Lysyl Oxidase Oxidizes Cell Membrane Proteins and Enhances the Chemotactic Response of Vascular Smooth Muscle Cells (2008)

Lysyl oxidase (LOX) is a potent chemokine inducing the migration of varied cell types. Here we demonstrate that inhibition of LOX activity by beta-aminopropionitrile (BAPN) in cultured rat aortic smooth muscle cells (SMCs) reduced the chemotactic response and sensitivity of these cells toward LOX and toward PDGF-BB. The chemotactic activity of PDGF-BB was significantly enhanced in the presence of a non-chemotactic concentration of LOX. We considered the possibility that extracellular LOX may oxidize cell surface proteins, including the PDGF receptor-beta (PDGFR-beta), to affect PDGF-BB-induced chemotaxis. Plasma membranes purified from control SMC contained oxidized PDGFR-beta. The oxidation of this receptor and other membrane proteins was largely prevented in cells preincubated with BAPN. Addition of purified LOX to these cells restored the profile of oxidized proteins toward that of control cells. The high affinity and capacity for the binding of PDGF-BB by cells containing oxidized PDGFR-beta was diminished by approximately 2-fold when compared with cells in which oxidation by LOX was prevented by BAPN. Phosphorylated members of the PDGFR-beta-dependent signal transduction pathway, including PDGFR-beta, SHP2, AKT1, and ERK1/ERK2 (p44/42 MAPK), turned over faster in BAPN-treated than in control SMCs. LOX knock-out mouse embryonic fibroblasts mirrored the effect obtained with SMCs treated with BAPN. These novel findings suggest that LOX activity is essential to generate optimal chemotactic sensitivity of cells to chemoattractants by oxidizing specific cell surface proteins, such as PDGFR-beta.