gebhart/patrepeval huggingface dataset:
Identification, Purification, and Characterization of Monoacylglycerol Acyltransferase from Developing Peanut Cotyledons (2001)

Biosynthesis of diacylglycerols in plants occurs mainly through the acylation of lysophosphatidic acid in the microsomal membranes. Here we describe the first identification of diacylglycerol biosynthetic activity in the soluble fraction of developing oilseeds. This activity was NaF-insensitive and acyl-CoA-dependent. Diacylglycerol formation was catalyzed by monoacylglycerol (MAG) acyltransferase (EC ) that transferred an acyl moiety from acyl-CoA to MAG. The enzyme was purified by successive chromatographic separations on octyl-Sepharose, blue-Sepharose, Superdex-75, and palmitoyl-CoA-agarose to apparent homogeneity from developing peanut (Arachis hypogaea) cotyledons. The enzyme was purified to 6,608-fold with the final specific activity of 15.86 nmol min(-1) mg(-1). The purified enzyme was electrophoretically homogeneous, and its molecular mass was 43,000 daltons. The purified MAG acyltransferase was specific for MAG and did not utilize any other acyl acceptor such as glycerol, glycerol-3-phosphate, lysophosphatidic acid, and lysophosphatidylcholine. The K(m) values for 1-palmitoylglycerol and 1-oleoylglycerol were 16.39 and 5.65 micrometer, respectively. The K(m) values for 2-monoacylglycerols were 2- to 4-fold higher than that of the corresponding 1-monoacylglycerol. The apparent K(m) values for palmitoyl-, stearoyl-, and oleoyl-CoAs were 17.54, 25.66, and 9.35 micrometer, respectively. Fatty acids, phospholipids, and sphingosine at low concentrations stimulated the enzyme activity. The identification of MAG acyltransferase in oilseeds suggests the presence of a regulatory link between signal transduction and synthesis of complex lipids in plants.
A Practical Chromogenic Procedure for the Detection of Homozygotes and Heterozygous Carriers of Niemann-Pick Disease (1975)

Niemann-Pick disease is caused by a deficiency of sphingomyelinase in organs and tissues. Determinations of sphingomyelinase activity had required the use of sphingomyelin labeled with radiocarbon or radiohydrogen. These materials are expensive, and their use is restricted to laboratories with radioactive counting facilities. An analogue of sphingomyelin, 2-hexadecanoylamino-4-nitrophenylphosphorylcholine, was synthesized. This substance is hydrolyzed by highly purified sphingomyelinase, and by sphingomyelinease in extracts of human liver tissue, cultured skin fibroblasts, cultured amniotic cells and washed leukocyte preparations. Extracts of tissues and cells from patients with Niemann-Pick disease Type A do not hydrolyze this compound, whereas heterozygotes and patients with Niemann-Pick disease Type C have an intermediate level of hydrolytic activity. Thus, the analogue is a reliable chromogenic reagent for the diagnosis of patients with Niemann-Pick disease and the detection of heterozygous carriers of the Niemann-Pick trait.
The impact of rare variation on gene expression across tissues (2017)

Rare genetic variants are abundant in humans and are expected to contribute to individual disease risk. While genetic association studies have successfully identified common genetic variants associated with susceptibility, these studies are not practical for identifying rare variants. Efforts to distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identify deleterious protein-coding alleles, but no analogous code exists for non-coding variants. Therefore, ascertaining which rare variants have phenotypic effects remains a major challenge. Rare non-coding variants have been associated with extreme gene expression in studies using single tissues, but their effects across tissues are unknown. Here we identify gene expression outliers, or individuals showing extreme expression levels for a particular gene, across 44 human tissues by using combined analyses of whole genomes and multi-tissue RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release. We find that 58% of underexpression and 28% of overexpression outliers have nearby conserved rare variants compared to 8% of non-outliers. Additionally, we developed RIVER (RNA-informed variant effect on regulation), a Bayesian statistical model that incorporates expression data to predict a regulatory effect for rare variants with higher accuracy than models using genomic annotations alone. Overall, we demonstrate that rare variants contribute to large gene expression changes across tissues and provide an integrative method for interpretation of rare variants in individual genomes.
Effect of dose and modification of viscous properties of oat gum on plasma glucose and insulin following an oral glucose load (1994)

An extract from oats known as oat gum (OG) is composed mainly of the polysaccharide (1-->3) (1-->4)-beta-D-glucan, which is highly viscous in aqueous solution. Viscous polysaccharides are known to attenuate postprandial plasma glucose and insulin responses. The purposes of this study were to determine the dose-response to OG and establish quantitatively the effect of viscosity on plasma glucose and insulin levels of healthy humans consuming 50 g glucose. Increasing the dose of OG successively reduced the plasma glucose and insulin responses relative to a control without gum. Reduction of the viscosity of OG by acid hydrolysis reduced or eliminated the capacity to decrease postprandial glucose and insulin levels. The ability of OG to modify glycaemic response was unchanged following agglomeration in the presence of maltodextrin. Agglomerated gum dispersed smoothly in a drink without formation of lumps, and development of maximum viscosity was delayed. These properties improve palatability. There was a highly significant linear relationship between log[viscosity] of the mixtures consumed and the glucose and insulin responses. The relationship shows that 79-96% of the changes in plasma glucose and insulin are attributable to viscosity, and that changes occur at relatively low doses and viscosities.
An all-optical computer network: lessons learned (1992)

Rainbow-1, an all-optical WDMA network capable of supporting up to 1000 nodes, each operating at 1 Gb/s sustained bit rate, is described. The expression all-optical stems from the fact that in these systems the path between nodes has electronic signal-handling only at the two ends. The path between nodes may be topologically complex, but it is all optical. The all-optical approach opens up the possibility of systems with thousands of users per link or network, each running at gigabit speeds, and employing electronic and photonic components whose speed need not be greater than the per-node bit rate. The lessons learned by building the Rainbow-1 WDMA network are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phase I and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer. (2001)

This Phase I study of MMI270, an p.o. administered matrix metalloproteinase inhibitor, assessed toxicity, pharmacokinetics, and tumor response data and investigated markers of biological activity to recommend a dose for Phase II studies. MMI270 was administered continuously at seven dose levels (50 mg once daily to 600 mg three times/day). Patients were evaluated for toxicity and tumor response, and blood and urine samples were taken for pharmacokinetics, bone resorption markers, direct targets of the inhibitor [matrix metalloproteinase-2 (MMP-2), MMP-8, and MMP-9], indirect targets [tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, basic fibroblast growth factor, vascular endothelial growth factor, vascular cell adhesion molecule-1, soluble urokinase plasminogen activator receptor, and cathepsins B and H] and for a tumor necrosis factor-alpha cytokine release assay. Ninety-two patients were entered. There was no myelotoxicity. Eighteen patients developed a widespread maculopapular rash, which increased in frequency and severity at doses > or = 300 mg bid. Thirty nine patients developed musculoskeletal side effects, which were related to duration of treatment, not to dose level. Pharmacokinetics were linear, and MMI270 was rapidly absorbed and eliminated with minimal accumulation on chronic dosing. Sustained plasma concentrations in excess of 4 x mean IC(50) for the target enzymes were observed at dose levels > or = 150 mg bid. There were no tumor regressions; however, 19 patients had stable disease for > or = 90 days. There was a dose-response increase of MMP-2 and TIMP-1 with MMI270. Transient effects on the bone resorption markers were detected. MMI270 was generally well tolerated, with adequate plasma levels for target enzyme inhibition. The two main toxicities were rash, resulting in a maximum tolerated dose of 300 mg bid and musculoskeletal side effects. Biological marker data indicate drug effects. The rise in TIMP-1 suggests that a reflex rise in inhibitors could modify the effects of MMI270. The recommended Phase II dose is 300 mg bid.
Pneumococcal conjugate vaccines (1999)

From the National Public Health Institute, Helsinki, Finland. Accepted for publication March 14, 1999. Reprints not available.
Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia (1993)

The independent significance of CD10 expression in childhood acute lymphoblastic leukemia (ALL) is uncertain because most studies have not adjusted for other risk features, such as age and immunophenotype, or for treatment effects. We reassessed the clinical importance of CD10 expression in patients who received highly effective contemporary treatment. CD10 antigen was detected in blast cells from 384 of 408 patients (94%) with B-lineage ALL and 36 of 90 (40%) with T-cell ALL. In the B-lineage subgroup, CD10 expression was associated with favorable presenting features: age > or = 1 year, lower leukocyte count (< 50 x 10(9)/l), and leukemic cell DNA index > or = 1.16 or hyperdiploidy > 50 chromosomes. One-half of the patients with CD10- B-lineage ALL had 11q23 chromosomal abnormalities. Separate analysis of the marker in T-cell ALL revealed no differences between CD10+ and CD10- cases in clinical features or karyotypic patterns, with the exception of a lower frequency of central nervous system leukemia and a higher frequency of 9p abnormalities in the former subgroup. CD10+ T-cell cases were also significantly more likely than CD10- cases to coexpress CD21, CD1, CD4, or CD8. Lack of CD10 expression was independently associated with an adverse prognosis in T-cell ALL (p = 0.02). However, for the larger subgroup of patients with B-lineage ALL, CD10 expression has no independent prognostic significance.
Two novel fully complementary self-biased CMOS differential amplifiers (1991)

Two CMOS differential amplifiers, one that is intended for applications in which the input common-mode range is relatively limited, the complementary self-biased differential amplifier (CSDA), and one that is intended for applications in which the input common-mode range is bounded only by the supply voltages, the very-wide-common-mode-range differential amplifier (VCDA), are discussed. Both differ from conventional CMOS differential amplifiers in having fully complementary configurations and in being self-biased through negative feedback. The amplifiers have been applied as precision high-speed comparators in commercial VLSI CMOS integrated circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sleep Propensity Free-Runs with the Temperature, Melatonin and Cortisol Rhythms in a Totally Blind Person (1992)

In previous studies, we found that many totally blind people have free-running melatonin rhythms, but that free-running melatonin rhythms were not necessarily associated with periodic insomnia and daytime sleepiness. Thus, it was not clear if the circadian sleep propensity rhythm was free-running with the other circadian rhythms. In the present study, we report that the sleep propensity rhythm (as defined by an ultrashort sleep-wake schedule) free-ran with the melatonin, temperature and cortisol rhythms in a 44-year-old totally blind man even though he maintained a conventional sleep schedule and did not complain of clinically significant insomnia or excessive daytime sleepiness.
Steganography: Past, Present, Future (2001)

Steganography (a rough Greek translation of the term Steganography is secret writing) has been used in various forms for 2500 years. It has found use in variously in military, diplomatic, personal and intellectual property applications. Briefly stated, steganography is the term applied to any number of processes that will hide a message within an object, where the hidden message will not be apparent to an observer. This paper will explore steganography from its earliest instances through potential future application.
Suicide Gene Therapy (2003)

Radiotherapy (RT) is a primary treatment modality for the majority of solid tumors. The objective is to destroy the tumor mass by exposure to ionizing radiation (IR) from an external beam or isotopic source. IR causes DNA damage directly and indirectly via the production of reactive oxygen intermediates (ROIs). Accumulation of sufficient damage leads to tumor cell death. The efficacy of RT is usually governed by the radiation dose given, the main limitation being the need to avoid injury to the surrounding normal tissues. To address the latter problem, physical techniques such as conformal and intensity-modulated radiotherapy have been developed to improve the precision of dose delivery to the tumor volume. However, some tumors prove refractory to conventional radiotherapy treatments, as insufficient dose can be delivered to the tumor. In such cases, other therapeutic strategies, such as chemotherapy, can be used in combination, particularly if such drugs lead to increased tumor radiosensitization. Nevertheless, many tumor types, (e.g., glioblastoma) are often resistant to even these combined approaches. Consequently, there is a need for new strategies that can improve the effectiveness of current radiotherapy regimens. Gene therapy offers the exciting possibility of significantly improving the efficacy of radiotherapy without the need for IR-dose escalation or undue increases in normal tissue morbidity. Furthermore, the potential to spatially and temporally target the activation of gene therapy vectors using clinically relevant IR doses provides a particularly attractive prospect.
WebFEATURE: an interactive web tool for identifying and visualizing functional sites on macromolecular structures (2003)

WebFEATURE (http://feature.stanford.edu/webfeature/) is a web-accessible structural analysis tool that allows users to scan query structures for functional sites in both proteins and nucleic acids. WebFEATURE is the public interface to the scanning algorithm of the FEATURE package, a supervised learning algorithm for creating and identifying 3D, physicochemical motifs in molecular structures. Given an input structure or Protein Data Bank identifier (PDB ID), and a statistical model of a functional site, WebFEATURE will return rank-scored 'hits' in 3D space that identify regions in the structure where similar distributions of physicochemical properties occur relative to the site model. Users can visualize and interactively manipulate scored hits and the query structure in web browsers that support the Chime plug-in. Alternatively, results can be downloaded and visualized through other freely available molecular modeling tools, like RasMol, PyMOL and Chimera. A major application of WebFEATURE is in rapid annotation of function to structures in the context of structural genomics.
Retromer maintains basolateral distribution of the type II TGF-β receptor via the recycling endosome (2013)

Transforming growth factor β (TGF-β) is critical for the development and maintenance of epithelial structures. Because receptor localization and trafficking affect the cellular and organismal response to TGF-β, the present study was designed to address how such homeostatic control is regulated. To that end, we identify a new role for the mammalian retromer complex in maintaining basolateral plasma membrane expression of the type II TGF-β receptor (TβRII). Retromer and TβRII associate in the presence or absence of TGF-β ligand. After retromer knockdown, although TβRII internalization and trafficking to a Rab5-positive compartment occur as in wild-type cells, receptor recycling is inhibited. This results in TβRII mislocalization from the basolateral to both the basolateral and apical plasma membranes independent of Golgi transit and the Rab11-positive apical recycling endosome. The data support a model in which, after initial basolateral TβRII delivery, steady-state polarized TβRII expression is maintained by retromer/TβRII binding and delivery to the common recycling endosome.
Efficient hierarchical graph-based video segmentation (2010)

We present an efficient and scalable technique for spatiotemporal segmentation of long video sequences using a hierarchical graph-based algorithm. We begin by over-segmenting a volumetric video graph into space-time regions grouped by appearance. We then construct a “region graph” over the obtained segmentation and iteratively repeat this process over multiple levels to create a tree of spatio-temporal segmentations. This hierarchical approach generates high quality segmentations, which are temporally coherent with stable region boundaries, and allows subsequent applications to choose from varying levels of granularity. We further improve segmentation quality by using dense optical flow to guide temporal connections in the initial graph. We also propose two novel approaches to improve the scalability of our technique: (a) a parallel out-of-core algorithm that can process volumes much larger than an in-core algorithm, and (b) a clip-based processing algorithm that divides the video into overlapping clips in time, and segments them successively while enforcing consistency. We demonstrate hierarchical segmentations on video shots as long as 40 seconds, and even support a streaming mode for arbitrarily long videos, albeit without the ability to process them hierarchically.
Direct injection of noise to the visual cortex decreases accuracy but increases decision confidence (2011)

The relationship between accuracy and confidence in psychophysical tasks traditionally has been assumed to be mainly positive, i.e., the two typically increase or decrease together. However, recent studies have reported examples of exceptions, where confidence and accuracy dissociate from each other. Explanations for such dissociations often involve dual-channel models, in which a cortical channel contributes to both accuracy and confidence, whereas a subcortical channel only contributes to accuracy. Here, we show that a single-channel model derived from signal detection theory (SDT) can also account for such dissociations. We applied transcranial magnetic stimulation (TMS) to the occipital cortex to disrupt the internal representation of a visual stimulus. The results showed that consistent with previous research, occipital TMS decreased accuracy. However, counterintuitively, it also led to an increase in confidence ratings. The data were predicted well by a single-channel SDT model, which posits that occipital TMS increased the variance of the internal stimulus distributions. A formal model comparison analysis that used information theoretic methods confirmed that this model was preferred over single-channel models, in which occipital TMS changed the signal strength or dual-channel models, which assume two different processing routes. Thus our results show that dissociations between accuracy and confidence can, at least in some cases, be accounted for by a single-channel model.
PLATELET ACTIVATING FACTOR (PAF) RECEPTOR IS INVOLVED IN ENDOTOXIN-INDUCED CGRP RELEASE FROM RAT MESENTERIC ARTERIAL BED (MAB) (1995)

Inst. of Vascular Medicine, Third Hospital, Beijing Medical Univ., Beijing, China, 100083, & Univ. Kentucky Med. Ctr., Lexington, KY, USA.
Real-time probabilistic segmentation for segment-based speech recognition (1998)

In this work, we investigate modifications to a probabilistic segmentation algorithm to achieve a real-time, and pipelined capability for our segment-based speech recognizer [4]. The existing algorithm used a Viterbi and backwards A search to hypothesize phonetic segments [2]. We were able to reduce the computational requirements of this algorithm by reducing the effective search space to acoustic landmarks, and were able to achieve pipelined capability by executing theA search in blocks defined by reliably detected phonetic boundaries. The new algorithm produces 30% fewer segments, and improves TIMIT phonetic recognition performance by 2.4% over an acoustic segmentation baseline. We were also able to produce 30% fewer segments on a word recognition task in a weather information domain [11].
Sizing the Emerging Global Labor Market: (2006)

Executive Overview Offshoring is a growing phenomenon. Increasingly, companies based in high-wage economies are hiring skilled workers in lower-wage economies to undertake service tasks that can be performed remotely, such as IT maintenance and call center operation. Today, improvements in information technology and falling telecommunication costs mean that any activity that is not tied to a particular place by the need for customer contact, or local knowledge, or complex, face-to-face interactions with colleagues can—in theory—be performed remotely. Thanks to freer trade between countries and a reduction in the perceived risks of operating overseas, companies can choose to perform such an activity in a lower-cost offshore location, if that seems advantageous, either by outsourcing to a third party vendor, or by developing its own, captive operation. Both choices comprise what we know as “offshoring.”
Cardiomyocyte Apoptosis Triggered by RAFTK/pyk2 via Src Kinase Is Antagonized by Paxillin (2004)

Altered cellular adhesion and apoptotic signaling in cardiac remodeling requires coordinated regulation of multiple constituent proteins that comprise cytoskeletal focal adhesions. One such protein activated by cardiac remodeling is related adhesion focal tyrosine kinase (RAFTK, also known as pyk2). Adenoviral-mediated expression of RAFTK in neonatal rat cardiomyocytes involves concurrent increases in phosphorylation of Src, c-Jun N-terminal kinase, and p38 leading to characteristic apoptotic changes including cleavage of poly(ADP-ribose) polymerase, caspase-3 activation, and increased DNA laddering. DNA laddering was decreased by mutation of the Tyr(402) Src-binding site in RAFTK, suggesting a central role for Src activity in apoptotic cell death that was confirmed by adenoviral-mediated Src expression. Multiple apoptotic signaling cascades are recruited by RAFTK as demonstrated by prevention of apoptosis using caspase-3 inhibitor IV (caspase-3 specific inhibitor), PP2 (Src-specific kinase inhibitor), or Csk (cellular negative regulator for Src), as well as dominant negative constructs for p38beta or MKP-1. These RAFTK-mediated phenotypic characteristics are prevented by concurrent expression of wild-type or a phosphorylation-deficient paxillin mutated at Tyr(31) and Tyr(118). Wild-type or mutant paxillin protein accumulation in the cytoplasm has no overt effect upon cell structure, but paxillin accumulation prevents losses of myofibril organization as well as focal adhesion kinase, vinculin, and paxillin protein levels mediated by RAFTK. Apoptotic signaling cascade inhibition by paxillin indicates interruption of signaling proximal to but downstream of RAFTK activity. Chronic RAFTK activation in cardiac remodeling may represent a maladaptive reactive response that can be modulated by paxillin, opening up novel possibilities for inhibition of cardiomyocyte apoptosis and structural degeneration in heart failure.