gebhart/patrepeval huggingface dataset:
Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms (1997)

Exogenous administration of glucagon-like peptide-1-(7—36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin(9—39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.
Monitoring the acute phase response. (1988)

Local damage to tissue invokes a systemic response that includes fever, a neutrophil leucocytosis, and an increase in
Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies (2002)

Targeting angiogenesis represents a new strategy for the development of anticancer therapies. New targets derived from proliferating endothelial cells may be useful in developing anticancer drugs that prolong or stabilize the progression of tumors with minimal systemic toxicities. These drugs may also be used as novel imaging and radiommunotherapeutic agents in cancer therapy. In this review, the mechanisms and control of angiogenesis are discussed. Genetic and proteomic approaches to defining new potential targets on tumor vasculature are then summarized, followed by discussion of possible antiangiogenic treatments that may be derived from these targets and current clinical trials. Such strategies involve the use of endogenous antiangiogenic agents, chemotherapy, gene therapy, antiangiogenic radioligands, immunotherapy, and endothelial cell-based therapies. The potential biologic end points, toxicities, and resistance mechanisms to antiangiogenic agents must be considered as these therapies enter clinical trials.
Why Nature Chose Phosphates (1987)

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO3- as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.
Regulation of Hexokinase II Gene Expression by Glucose Flux in Skeletal Muscle (1996)

1) due to relative mild insulinopenia, HK II expression is decreased in non-GLUT4-overexpressing tissues of MLC-GLUT4 mice compared to age/sex-matched controls, and 2) GLUT4-mediated increase in cellular glucose flux can prevent the decrease in HK II expression (in GLUT4-overexpressing tissues) as a result of relative mild insulinopenia. Indeed, during the process of aging, the return of circulating insulin levels of MLC-GLUT4 mice to normal levels is associated with the normalization of HK II expression in all tissues of MLC-GLUT4 and age/sex-matched control mice. We propose that: 1) glucose flux has an amplifying effect on the ability of insulin to stimulate skeletal muscle HK II gene expression and 2) insulin-dependent glucose flux may be a potential mechanism by which HK II gene expression is regulated by sensitivity to insulin.
LacZ inducible, antigen/MHC-specific T cell hybrids (1994)

The nuclear factor of activated T cells (NFAT) enhancer element of the IL-2 gene can regulate expression of the Escherichia coli lacZ reporter gene in activated T cells. Based upon this observation, we showed that this inducible NFAT--lacZ construct could be used to measure TCR mediated, ligand-specific activation in single T cells. Here we describe a general approach to obtaining lacZ inducible, T cell hybrids by generating two new fusion partners BWZ.36 and BWZ.36 CD8 alpha derived by transfecting alpha-beta-BW5147 cells with the NFAT--lacZ construct. Using these fusion partners and normal T cells from immunized mice, we obtained T cell hybrids in which lacZ activity is specifically induced in response to antigen/MHC class II or MHC class I complexes. We show that measuring ligand induced T cell activation by the non-radioactive lacZ assay is simpler, faster, and most cost-effective relative to conventional IL-2 assays. Most importantly, the unique ability to detect activation of single T cells by the lacZ assays permits detection of rare antigen presenting cells and thus provides the basis for developing expression cloning strategies for identifying unknown T cell antigens.
Reaction of water with hydrofluoric acid treated silicon(111) and (100) surfaces (1989)

Si wafers with (100) or (111) oriented surfaces were treated in hydrofluoric acid (40% HF, 1 min) and then water rinsed for different times from 10 s to more than 50 h. Oxygen uptake and oxide formation were investigated by x-ray photoelectron spectroscopy and high-resolution electron energy-loss spectroscopy. The initial state after the HF dip is characterized by a coverage with Si–hydride and small amounts of oxygen and fluorine. The interaction with the liquid phase of water was investigated up to the monolayer range. It shows distinct features: The first step is a rapid exchange of Si–F with H2 O to form Si–OH groups followed by a slow nucleophilic attack of OH− on surface Si–H to produce Si–OH. Growth law is logarithmic and extends to 3–5 h of water contact. The surface Si–OH act as nuclei for the attack of water on the polarized Si–SiOH backbonds. Interior Si–H and Si–OH groups develop. Further attack of OH− on interior Si–H yields Si–OH. Condensation of Si–OH forms Si–O–Si bridges and SiO2−x nuclei appear. Strain and altered surface topography lead to a changed rate of the logarithmic oxide growth. The oxide formation is accompanied by a slight corrosive attack of H2 O, leading to roughening of the surface.
Automated Solid-Phase Synthesis of Oligosaccharides (2001)

Traditionally, access to structurally defined complex carbohydrates has been very laborious. Although recent advancements in solid-phase synthesis have made the construction of complex oligosaccharides less tedious, a high level of technical expertise is still necessary to obtain the desired structures. We describe the automated chemical synthesis of several oligosaccharides on a solid-phase synthesizer. A branched dodecasaccharide was synthesized through the use of glycosyl phosphate building blocks and an octenediol functionalized resin. The target oligosaccharide was readily obtained after cleavage from the solid support. Access to certain complex oligosaccharides now has become feasible in a fashion much like the construction of oligopeptides and oligonucleotides.
The Lymphotoxin-α (LTα) Subunit Is Essential for the Assembly, but Not for the Receptor Specificity, of the Membrane-anchored LTα1β2 Heterotrimeric Ligand (1997)

The lymphotoxins (LT) alpha and beta, members of the tumor necrosis factor (TNF) cytokine superfamily, are implicated as important regulators and developmental factors for the immune system. LTalpha is secreted as a homotrimer and signals through two TNF receptors of 55-60 kDa (TNFR60) or 75-80 kDa (TNFR80). LTalpha also assembles with LTbeta into a membrane-anchored, heterotrimeric LTalpha1beta2 complex that engages a distinct cognate receptor, the LTbeta receptor (LTbetaR). To investigate the role of the LTalpha subunit in the function of the membrane LTalpha1beta2 complex, gene transfer via baculovirus was used to assemble LTalpha and -beta complexes in insect cells. LTalpha containing mutations at D50N or Y108F are secreted as homotrimers that fail to bind either TNF receptor and are functionally inactive in triggering cell death of the HT29 adenocarcinoma cell line. In contrast, these mutant LTalpha proteins retain the ability to co-assemble with LTbeta into membrane-anchored LTalpha1beta2 complexes that engage the LTbetaR and trigger the death of HT29 cells. Membrane-anchored LTbeta expressed on the cell surface in absence of the LTalpha subunit binds the LTbetaR but is functionally inactive in the cell death assay. These results indicate that the TNF receptor-binding regions of the LTalpha subunit are not necessary for engagement of the LTbetaR, but the LTalpha subunit is required for the assembly of LTbeta into a functional heteromeric ligand.
Mass Spectrometry (LC–MS/MS) Identified Proteomic Biosignatures of Breast Cancer in Proximal Fluid (2012)

We have begun an early phase of biomarker discovery in three clinically important types of breast cancer using a panel of human cell lines: HER2 positive, hormone receptor positive and HER2 negative, and triple negative (HER2-, ER-, PR-). We identified and characterized the most abundant secreted, sloughed, or leaked proteins released into serum free media from these breast cancer cell lines using a combination of protein fractionation methods before LC-MS/MS mass spectrometry analysis. A total of 249 proteins were detected in the proximal fluid of 7 breast cancer cell lines. The expression of a selected group of high abundance and/or breast cancer-specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis. Interestingly, mass spectrometry identified a cathepsin D protein single-nucleotide polymorphism (SNP) by alanine to valine replacement from the MCF-7 breast cancer cell line. Comparison of each cell line media proteome displayed unique and consistent biosignatures regardless of the individual group classifications, demonstrating the potential for stratification of breast cancer. On the basis of the cell line media proteome, predictive Tree software was able to categorize each cell line as HER2 positive, HER2 negative, and hormone receptor positive and triple negative based on only two proteins, muscle fructose 1,6-bisphosphate aldolase and keratin 19. In addition, the predictive Tree software clearly identified MCF-7 cell line overexpresing the HER2 receptor with the SNP cathepsin D biomarker.
Structure-function analysis of angiotensin I-converting enzyme using monoclonal antibodies. Selective inhibition of the amino-terminal active site. (1994)

Angiotensin I-converting enzyme (ACE; kininase II) contains two very similar domains (the NH2- and COOH-terminal domains (N and C domains, respectively)), each bearing an active site. These active sites hydrolyze the same peptides, but do not have the same catalytic properties and substrate specificities. In an attempt to develop domain-specific immunological probes, two series of monoclonal antibodies (mAbs), 19 clones in all, were produced and tested against human ACE. These mAbs recognized at least nine different epitopes within three antigenic regions of the ACE molecule. Testing on wild-type recombinant ACE and several mutants with only one intact domain showed that these epitopes were all located in the N domain. None of the mAbs recognized the C domain. This particular specificity and analysis of results obtained with several polyclonal antibodies to human ACE suggest that ACE immunogenicity is determined mainly by the N domain. Two mAbs (3A5 and i2H5) recognizing epitopes from different antigenic regions of ACE inhibited the enzymatic activity of the N (but not of the C) domain. mAb 3A5 had the same inhibitory potency toward hippuryl-His-Leu, benzyloxycarbonyl-Phe-His-Leu, and angiotensin I hydrolysis, with 50% inhibition achieved at a mAb/ACE molar ratio of 6. mAb i2H5 was roughly three times more effective than mAb 3A5 inhibiting the hydrolysis of benzyloxycarbonyl-Phe-His-Leu and the natural substrates angiotensin I and bradykinin (50% inhibition at a molar ratio of 1-2), but was less effective in inhibiting hippuryl-His-Leu cleavage (50% inhibition at a molar ratio of 22-25), indicating that this substrate interacts with a specific subsite. mAb i2H5 almost completely inhibited the hydrolysis of the luteinizing hormone-releasing hormone by the isolated N domain. Both the primary carboxyl- and amino-terminal cleavages of this peptide were suppressed. This antibody suppressed the primary amino-terminal cleavage of the luteinizing hormone-releasing hormone by wild-type ACE by > 90%, indicating that this particular ACE function is mediated mainly by the N domain active site. These data provide evidence for structural differences between the two homologous domains of ACE despite their high degree of sequence homology and show that monoclonal antibodies are able to distinguish between the two active sites in ACE.
Public key management for network security (1987)

A tutorial is given on two public key cryptographic systems that provide an alternative to classical cryptographic key management techniques: the RSA system and the SEEK system. The certification of public numbers is discussed.
Epoxy Reinforced Aerogels Made Using a Streamlined Process (2010)

Reinforcing silica aerogels by conformally coating the nanoskeleton with a polymer has been demonstrated to be an effective way to improve mechanical properties. In addition, the mesoporosity and low thermal conductivity is maintained, making this robust form of aerogel an enabling material for a variety of aerospace applications. However, the process for making the aerogels can be quite long, involving production of the gel, solvent exchanges, and diffusion of monomer, followed by more solvent exchanges and supercritical fluid extraction. This paper for the first time compares a synthetic scheme that shortens the process to make epoxy reinforced aerogels by eliminating monomer diffusion and half of the solvent washes to the previously described diffusion-controlled process. The ethanol-soluble epoxy monomers are included in the initial step of the sol−gel process without interfering with gelation of the starting silanes. Notably, properties of aerogels made using a low amount of amine reactive sites have properties similar to those previously reported that used the longer diffusion controlled process, whereas higher amounts of amine sites produce less desirable monoliths with much higher density and lower surface areas.
The Attentive Brain (1995)

in&amp;apos;s face (A) is seen through small apertures (B), its meaning as a face is greatly degraded. ears sequentially. To process a pattern of sounds as a whole, it must be &amp;quot;recoded&amp;quot;. Such a recoding, or processing stage, is often called a working memory, which stores short-termmemory traces. To identify familiar events, the brain compares short-term traces with stored categories. These categories are accessed using long-term-memory traces, which represent previous experiences that have been acquired through learning. Somehow, we can rapidly learn new facts--placing them in long-term memory--without being forced just as rapidly to forget others. How does brain processing keep old memories stable and still maintain enough plasticity to learn new things? What I call the stabilityplasticity dilemma must be solved by every brain system that attempts to learn about the flood of external signals. I shall examine several challenging examples of visual and auditory data that suggest how the brain mi
Audio coding using a psychoacoustic pre- and post-filter (2002)

A novel concept for perceptual audio coding is presented which is based on the combination of a pre- and post-filter, controlled by a psychoacoustic model, with a transform coding scheme. This paradigm allows modeling of the temporal and spectral shape of the masked threshold with a resolution independent of the used transform. By using frequency warping techniques the maximum possible detail for a given filter order can be made frequency-dependent and thus better adapted to the human auditory system. The filter coefficients are represented efficiently by LSF parameters which can be adaptively interpolated over time. First experiments with a system obtained by extending an existing transform codec showed that this approach can significantly improve the performance for speech signals, while the performance for other signals remained the same.
Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver (2009)

To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivatives, and human tissues allowed us to identify several trends during hESC and in vivo liver differentiation. First, differentiation results in DNA methylation changes at a minimal number of assayed regions, both in vitro and in vivo (2%-11%). Second, in vitro hESC differentiation is characterized by both de novo methylation and demethylation, whereas in vivo fetal liver development is characterized predominantly by demethylation. Third, hESC differentiation is uniquely characterized by methylation changes specifically at H3K27me3-occupied regions, bivalent domains, and low density CpG promoters (LCPs), suggesting that these regions are more likely to be involved in transcriptional regulation during hESC differentiation. Although both H3K27me3-occupied domains and LCPs are also regions of high variability in DNA methylation state during human liver development, these regions become highly unmethylated, which is a distinct trend from that observed in hESCs. Taken together, our results indicate that hESC differentiation has a unique DNA methylation signature that may not be indicative of in vivo differentiation.
Formation of hydroxyvitamin K by vitamin K epoxide reductase of warfarin-resistant rats. (1983)

A new metabolite of vitamin K, 2(3)-hydroxy-2,3-dihydro-2-methyl,3-phytyl-1,4-naphthoquinone (hydroxyvitamin K), has been identified as a product of vitamin K epoxide metabolism in hepatic microsomes from warfarin-resistant rats, but not in those derived from normal rats. The structure was determined by comparison of the high performance liquid chromatography retention times, UV, IR, CD, and mass spectra of the unknown with chemically synthesized standards. Alterations in the formation of hydroxyvitamin K occur in parallel with alterations in total vitamin K epoxide conversion with respect to reaction time, extent of reaction, detergent stimulation, and inhibition by warfarin. Thus, hydroxyvitamin K appears to be a product of the warfarin-resistant vitamin K epoxide reductase. It is neither a substrate nor an inhibitor of epoxide reduction. Hydroxyvitamin K is formed from both enantiomers of racemic vitamin K epoxide with little stereoselectivity for the configuration of either the oxirane ring or the phytyl side chain. The reaction is stereospecific; however, the biologically formed (+)-vitamin K epoxide yields exclusively (+)-3-hydroxyvitamin K. Observation of this product is discussed as a key to understanding the normal reaction mechanism of the enzyme.
Hypertonic sucrose inhibition of endocytic transport suggests multiple early endocytic compartments (1988)

Incubation of animal cells with hypertonic sucrose and polyethylene glycol (PEG) 1,000 renders endosomes sensitive in situ to hypotonic shock (Okada and Rechsteiner, 1982). We found that: 1) in vitro endosomes were osmotically insensitive; and 2) hypertonic sucrose inhibited transport from very early endosomes to lysosomes. Endocytic vesicles were labeled by incubating Chinese hamster ovary (CHO) cells for 1-10 min at 37 degrees C with horseradish peroxidase (HRP) and/or fluorescein isothiocyanate-conjugated dextran (FITC-dextran). Cell fractions prepared in 0.25 M sucrose were hypotonically shocked by dilution with 5 mM Na phosphate buffer, pH 6.7, to a final sucrose concentration of 0.05 M. After hypotonic shock, endocytized HRP and FITC-dextran pelleted with membrane while lysosomal hydrolases did not. The HRP activity in the pellet was latent, suggesting that endosomes were resistant to osmotic shock. Uptake in the presence of hypertonic sucrose had little effect on the subsequent osmotic sensitivity of the endosomes. Uptake in the presence of hypertonic sucrose and PEG 1,000 rendered endosomes fragile to cell homogenization. Unexpectedly, the inclusion of hypertonic sucrose in the uptake and chase media inhibited the appearance of HRP in lysosomes. HRP internalized during a 10-min uptake appeared as if it were present in two physically distinct compartments, one accessible to transport inhibition by exogenous sucrose ("very early" endosomes) and the other not ("early" endosomes). After a brief uptake (1-3 min), postincubation of CHO cells in 0.25 M sucrose-containing media completely blocked transport of internalized HRP to lysosomes. This blockage could be partially relieved by cointernalization of invertase with HRP. These results suggest that transport between multiple early endosome populations is sensitive to intraorganellar osmotic conditions.
Delay uncertainty due to on-chip simultaneous switching noise in high performance CMOS integrated circuits (2002)

On-chip parasitic inductance inherent to the power supply rails has become significant in high speed digital circuits. Therefore, current surges result in voltage fluctuations within the power distribution networks, creating delay uncertainty. On-chip simultaneous switching noise should therefore be considered when estimating the propagation delay of a CMOS logic gate in high speed synchronous CMOS integrated circuits. Analytical expressions characterizing the on-chip simultaneous switching noise voltage and the output voltage waveform of a CMOS logic gate driving both a capacitive and a resistive-capacitive load are presented. The waveform of the output voltage signal based on the analytical expressions is quite close to SPICE. The estimated propagation delay is within 5% as compared to SPICE while the average improvement in accuracy can reach 10% as compared to a delay estimated without considering on-chip simultaneous switching noise. The analytical expressions presented provide an accurate timing model for non-negligible on-chip simultaneous switching noise in high speed synchronous CMOS integrated circuits.