gebhart/patrepeval huggingface dataset:
Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes (2006)

Inhibitors of the enzyme dipeptidyl peptidase IV (DPP IV) provide a strategy for the treatment of type 2 diabetes. DPP IV rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP IV prolongs and enhances the activity of endogenous GLP-1 and GIP, which serve as important prandial stimulators of insulin secretion and regulators of blood glucose control. In clinical trials DPP IV inhibitors (or 'gliptins') have shown efficacy and tolerability in the management of hyperglycaemia in type 2 diabetes, without causing weight gain or hypoglycaemia.
An Efficient Synthesis of Aryl Phenaceturates Using Acid Catalyzed Dicyclohexylcarbodiimide Esterification and Transient<i>N</i>-<i>trent</i>-Butoxycarbonylation (1994)

Application of the Holmberg procedure (DCC/pyridine/p-TSAcat) improves the yield of the direct condensation of phenols with phenylacetylglycine (1). Moreover, N-tert-butoxycarbonylation of 1 impedes an intramolecular reaction leading to an oxazolone, and allows the formation of stable aryl N-Boc phenaceturates. Then, mild cleavage of the Boc group with four equivalents of trifluoroacetic acid furnishes the aryl phenylacetylglycinate. This indirect method is more efficient than its direct analog in the case of phenols possessing electron-withdrawing substituents.
A vertically integrated tunable UHF filter (2010)

A novel, vertically integrated filter design is used to produce a tunable UHF filter in a polymer based substrate. The filter is a sub band of a widely tunable narrowband preselect filter array and makes use of unused substrate space within the array to increase the overall tuning range of the array while keeping the substrate volume constant. This paper will discuss the use of mixed three dimensional electromagnetic and SPICE simulation in the design of the tunable filter. The fabrication of the filter using standard PCB fabrication techniques will be described and measured performance of the filter will be compared to the simulated response. The design and simulation of vertically integrated coupled parallel plate inductors and the careful design of the combination of static capacitors and tuning varactors to acheive the desired tuning and filter response will be highlighted.
In vivo uptake of lecithin‐coated polystyrene beads by rat hepatocytes and sinusoidal endothelial cells (1996)

Background While phagocytosis by Kupffer cells (stellate perisinusoidal macrophages) is well known and that by endothelial cells also is thought to occur under certain conditions, the uptake of large particles by hepatocytes has not been well studied. We reported previously the selective phagocytic uptake of material by hepatocytes using egg lecithin-coated silicon particles. In the present work, we describe more precisely this process following the injection of lecithin-coated polystyrene beads. Additionally, we consider the possible significance of the transcytotic action by endothelial cells. Methods Polystyrene latex beads (240 nm in diameter) composed of two layers of polystyrene and methyl methacrylate with a central void cavity and diameter of 140 nm were injected into male Wister-Imamichi rats. The injections were administered through the hepatic portal vein in a volume of 3 ml (concentration of the lecithin-coated or uncoated beads was 2 mg/ml). Controls received the lecithin alone at a concentration of 2 mg/ml. Liver samples were taken 5, 10, or 15 min after injection, fixed, and processed for ultrastructural analysis. Results Both lecithin-coated and noncoated beads were mainly incorporated in the Kupffer cells as well as in the endothelial cells. Bristle-coated invaginations were observed in the uptake by both cell types; however, noncoated invaginations were also active in the endothelial cells, especially on the surface facing the perisinusoidal space of Disse. Only coated beads were observed within the space or in the hepatocytes. Once taken up by the hepatocytes, the lecithin-coated beads were found either within lysosomes or in a free state in the cytoplasm. Conclusions Uptake of 240 nm lecithin-coated polystyrene beads was observed by Kupffer cells, endothelial cells and hepatocytes. These beads were considered to be transported across the endothelial cells by transcytosis. Pseudopodia and bristle-coated invaginations were not employed by the hepatocytes when incorporating the beads. © 1996 Wiley-Liss, Inc.
Cardiac troponin I measurement with the ACCESS® immunoassay system: analytical and clinical performance characteristics (1998)

We evaluated the ACCESS cardiac troponin I (cTnI) immunoassay as a marker for myocardial infarction (MI). Total imprecision was 6.0% to 13.5%, the minimum detectable concentration was 0.007 microg/L, and the limit of quantitation was 0.046 microg/L. Comparison of cTnI measurement between the ACCESS and Stratus systems (n = 114) showed a proportional difference: ACCESS cTnI = 0.0996 Stratus cTnI + 0.049 microg/L (r = 0.811). Fifty-nine of 61 ambulatory patients without cardiac symptoms had no detectable cTnI (95% range, 0.00 to 0.025 microg/L). The optimum cutoff for discriminating MI (n = 289, 45 with MI) was 0.15 microg/L by receiver operator characteristic curve analysis; at this cutoff, the ACCESS cTnI assay showed a sensitivity of 88.9% (95% CI, 79.7-98.1%) and specificity of 91.8% (95% CI, 88.4-95.2%). The ACCESS cTnI assay results showed 89.4% and 93.0% concordance with the MB isoenzyme of creatine kinase (CK-MB) mass and Stratus cTnI results, respectively, for classification of patients with suspected MI. The ACCESS cTnI assay appears to show sensitivity and specificity comparable with those of both CK-MB mass and Stratus cTnI assays for the diagnosis of MI in patients presenting within 12 h of onset of symptoms.
Tracking <i>N</i>‐Acetyllactosamine on Cell‐Surface Glycans In Vivo (2011)

In living color: Many mammalian glycans associated with signaling receptors contain terminal or penultimate N-acetyllactosamine. A highly specific method for labeling this disaccharide on cell-surface glycoproteins of live cultured cells and zebrafish embryos is reported. The two-step chemoenzymatic approach involves in situ fucosylation followed by a bioorthogonal click reaction (see scheme; α(1,3)FucT=α(1,3)-fucosyltransferase).
Design of a High-efficiency Fiber-to-chip Coupler with Reflectors (2016)

In this paper, an inversely tapered coupler with Bragg reflectors is reported for the first time. With appropriately positioned reflecting structures, our fiber-to-chip coupler can more efficiently transmit the light from fiber to a waveguide in a photonic integrated circuit (PIC). A numerical simulation evaluated the coupler’s efficiency with the reflector. Optimized parameters that maximize the efficiency of the coupler are also investigated. Simulation results show that the reflector with appropriate parameters enhances efficiency by up to 7 dB. Likewise, Bragg metal reflectors implemented by the conventional metallization process can also improve efficiency. It is also shown that the proposed reflector enhances the coupling efficiency in a double-tip taper coupler.
Nuclear transfer of adult and genetically modified fetal cells of the rat (2001)

The present study examines the handling, activation, and micromanipulation of rat eggs in an attempt to produce live young using nuclear transfer (NT) of adult and genetically modified rat fetal cells. Mature rat eggs cultured in calcium-free medium showed reduced rates (24%) of chromosomal dispersion ("spontaneous activation" characteristic of this species) compared with eggs cultured in calcium-containing medium (47%), but failed to survive micromanipulation procedures. High rates of parthenogenetic cleavage were obtained with chemical activation using ethanol/cycloheximide (65%) compared with other standard chemical activation methods (4-28%). This type of activation was also effective in reestablishing cleavage capability (19-71%), in a time-dependent manner, of spontaneously activated eggs arrested at a second prophase-like state. At most, two of four tested micromanipulation procedures were effective in producing NT embryos capable of morula or blastocyst development (14-16%) in vivo following transfer to mouse oviducts. NT blastocysts produced from cumulus cells and transfected rat fetal fibroblasts appeared morphologically and karyotypically normal (2n = 42). Nocodazole-assisted metaphase enucleation and piezoelectric-assisted donor cell injection produced significant and equivocal effects on survival and cleavage rates of reconstructed embryos but failed to significantly improve in vivo morula/blastocyst development rates (16-28%) compared with unassisted micromanipulation (16%). Live births have not yet been obtained from early cleavage stage embryos (n = 269) transferred to pseudopregnant recipient rat oviducts. Improvements in reconstituted NT embryo culture and transfer are required for these methods to be an effective means of transgenic rat production.
p38 Mitogen-Activated Protein Kinase and c-Jun-NH2-Terminal Kinase Regulate RANTES Production by Influenza Virus-Infected Human Bronchial Epithelial Cells (2000)

Airway epithelial cells which are the initial site of influenza virus (IV) infection are suggested to participate in airway inflammatory response by expressing various cytokines including RANTES; however, the intracellular signal that regulates RANTES expression has not been determined. In the present study, we examined the role of p38 mitogen-activated protein (MAP) kinase, extracellular signal-regulated kinase (Erk), and c-Jun-NH2-terminal kinase (JNK) in RANTES production by IV-infected human bronchial epithelial cells. The results showed that IV infection induced increases in p38 MAP kinase, and Erk and JNK phosphorylation and activity. SB 203580, PD 98059, and CEP-1347 attenuated IV-infection induced p38 MAP kinase activity, Erk activity, and JNK activity, respectively. SB 203580 and CEP-1347 attenuated RANTES production by 45.3% and 45.2%, respectively, but a combination of these inhibitors additively attenuated by 69.1%. In contrast, PD 98059 did not attenuate. Anti-IL-1alpha mAb, anti-IL-1beta mAb, anti-TNF-alpha mAb, anti-IL-8 mAb, anti-IFN-beta mAb, anti-RANTES mAb, and a combination of these mAbs did not affect IV infection-induced increases in p38 MAP kinase, Erk, and JNK phosphorylation, indicating that each cytokine neutralized by corresponding Ab was not involved in IV infection-induced phosphorylation of MAP kinases. N-acetylcysteine (NAC) did not affect IV infection-induced increases in MAP kinase phosphorylation, whereas NAC attenuated RANTES production by 18.2%, indicating that reactive oxygen species may act as a second messenger leading to RANTES production via p38 MAP kinase- and JNK-independent pathway. These results indicate that p38 MAP kinase and JNK, at least in part, regulate RANTES production by bronchial epithelial cells.
Enzyme-Substrate Intermediate Formation at Lysine 329 of Human Deoxyhypusine Synthase (1997)

Deoxyhypusine (Nepsilon-(4-aminobutyl)lysine) is the key intermediate in the posttranslational synthesis of the unique amino acid, hypusine (Nepsilon-(4-amino-2-hydroxybutyl)lysine). Deoxyhypusine synthase catalyzes the formation of deoxyhypusine by conjugation of the butylamine moiety of spermidine to the epsilon-amino group of one specific lysine residue of the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. However, in the absence of the eIF-5A precursor, catalysis involves only the NAD-dependent cleavage of spermidine to generate 1,3-diaminopropane and a putative 4-carbon amine intermediate that gives rise to Delta1-pyrroline. We have obtained evidence for a covalent enzyme-substrate intermediate that accumulates in the absence of the eIF-5A precursor. Incubation of human recombinant enzyme with [1, 8-3H]spermidine and NAD, followed by reduction with NaBH3CN, resulted in specific radiolabeling of the enzyme. The radioactive component in the reduced enzyme intermediate was identified as deoxyhypusine and was shown to occur at a single locus. The fact that labeled deoxyhypusine was found after treatment with a reducing agent suggests an intermediate with the butylamine moiety derived from spermidine attached through an imine linkage to the epsilon-amino group of a specific lysine residue of the enzyme. This residue has been identified as lysine 329. Separate experiments showing efficient transfer of labeled butylamine moiety from enzyme intermediate to eIF-5A precursor strongly support a reaction mechanism involving an imine intermediate.
A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation (2005)

TH9507 reduced truncal fat, improved the lipid profile and did not increase glucose levels in HIV-infected patients with central fat accumulation. TH9507 may be a beneficial treatment strategy in this population, but longer-term studies with more patients are needed to determine effects on VAT, treatment durability, and safety.
Binaural Reverberation Using Two Parallel Feedback Delay Networks (2010)

Correspondence should be addressed to Fritz Menzer (fritz.menzer@a3.epfl.ch)ABSTRACTBinaural reverberators often use a tapped delay line to model early reections, to which a delayed latereverberation tail is added. This paper introduces a reverberator structure where the early reections aremodeled using a feedback delay network (FDN) and the late reverberation is modeled by a second FDNin parallel. The impulse responses of both FDNs are highly overlapping, simulating the presence of di usereverberation from the beginning of the impulse response. A particular feature of this reverberator is thereproduction of rst and second order reections using only head related transfer functions (HRTFs) for thedirections of the rst order reections, allowing to reduce the computational complexity.
Coxsackievirus B3 vaccines: use as an expression vector for prevention of myocarditis (2008)

Coxsackievirus B3 (CVB3), a member of the Picornaviridae family, is considered to be one of the most important infectious agents to cause virus-induced myocarditis. Despite improvements in studying virus pathology, structure and molecular biology, as well as the diagnosis of this disease, there is still no virus-specific drug or vaccine in clinical use. During the last 20 years many investigations have been performed to develop classic and modern immunization techniques against CVB3-induced heart disease. One promising approach among others includes the insertion of coding sequences of cytokines into the viral genome. The application of an IFN-gamma-expressing recombinant coxsackievirus vector is especially efficient against CVB3-induced myocarditis. Beside direct IFN-gamma-mediated antiviral effects, the local and simultaneous expression of IFN-gamma by the virus itself activates the immune system in a strong and long-lasting manner, which protects animals completely against subsequent lethal infections independently of the age of the immunized individual and the route of vaccine administration.
Role in anaerobiosis of the isoenzymes for <i>Saccharomyces cerevisiae</i> fumarate reductase encoded by <i>OSM1</i> and <i>FRDS1</i> (2007)

Saccharomyces cerevisiae possesses both a cytoplasmic and a mitochondrial fumarate reductase, encoded by FRDS1 and OSM1, respectively. While previous studies have shown that mutants lacking FRDS1 and OSM1 cannot grow under anaerobiosis (Arikawa et al., 1998), the physiological role of fumarate reductase (FR) remains poorly understood. Here, we report that an osm1 frds1 mutant is unable to grow anaerobically, even with glutamate as a sole nitrogen source, when succinate can be produced by the TCA oxidative branch. We also show that the growth of the mutant is not restored by adding acetoin, an alternative sink for NADH oxidation, but it is at least partly restored by the addition of oxygen or menadione, which can oxidize FADH(2) in addition to NADH. These data indicate that the growth inhibition of the mutant is due to an inability to reoxidize FAD, rather than an indirect effect on NADH or an inability to produce succinate per se. During anaerobic growth, FRDS1 expression was two to eight times higher than that of OSM1, and fumarate reductase activity was higher in the osm1 mutant than in the frds1 mutant. FRDS1 expression was induced by anaerobiosis, and this induction was abolished in a rox1 mutant. We conclude that the formation of succinate is strictly required for the reoxidation of FADH(2) during anaerobiosis, and that it is regulated through the control of FRDS1 expression when oxygen is limiting. Based on these data, we discuss the potential role of fumarate reductase in the regeneration of the FAD-prosthetic group of essential flavoproteins.
Improved adaptive downlink for OFDM/SDMA-based wireless networks (2002)

A combined OFDM/SDMA approach substantially increases the capacity of wireless local networks while maintaining a feasible implementation complexity. In the downlink of OFDM/SDMA-based networks however, the standard channel inversion approach significantly boosts the transmit power. We introduce a low-complexity downlink OFDM/SDMA strategy, based on the combination of channel inversion and Tomlinson-Harashima (1971, 1972) pre-coding, which lowers the required transmit power by 4 dB. Additionally, adaptive loading of the subcarriers as a means for further lowering the required transmit power in the downlink of OFDM/SDMA networks utilizing the proposed pre-compensating strategy is studied. We derive an efficient closed-form expression for the optimal bit distribution and show that an additional 8.5 dB gain in transmit power can be achieved. Finally, a simplified loading algorithm is proposed which possesses a lower computational and signaling cost in return for a small performance penalty.
agriGO: a GO analysis toolkit for the agricultural community (2010)

Gene Ontology (GO), the de facto standard in gene functionality description, is used widely in functional annotation and enrichment analysis. Here, we introduce agriGO, an integrated web-based GO analysis toolkit for the agricultural community, using the advantages of our previous GO enrichment tool (EasyGO), to meet analysis demands from new technologies and research objectives. EasyGO is valuable for its proficiency, and has proved useful in uncovering biological knowledge in massive data sets from high-throughput experiments. For agriGO, the system architecture and website interface were redesigned to improve performance and accessibility. The supported organisms and gene identifiers were substantially expanded (including 38 agricultural species composed of 274 data types). The requirement on user input is more flexible, in that user-defined reference and annotation are accepted. Moreover, a new analysis approach using Gene Set Enrichment Analysis strategy and customizable features is provided. Four tools, SEA (Singular enrichment analysis), PAGE (Parametric Analysis of Gene set Enrichment), BLAST4ID (Transfer IDs by BLAST) and SEACOMPARE (Cross comparison of SEA), are integrated as a toolkit to meet different demands. We also provide a cross-comparison service so that different data sets can be compared and explored in a visualized way. Lastly, agriGO functions as a GO data repository with search and download functions; agriGO is publicly accessible at http://bioinfo.cau.edu.cn/agriGO/.
Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies. (2000)

Tumor cells may display a multidrug resistance phenotype by overexpression of ATP binding cassette transporter genes such as multidrug resistance (MDR) 1 P-glycoprotein (P-gp) or the multidrug resistance protein 1 (MRP1). MDR3 P-gp is a close homologue of MDR1 P-gp, but its role in MDR is probably minor and remains to be established. The MRP1 protein belongs to a family of at least six members. Three of these, i.e., MRP1, MRP2, and MRP3, can transport MDR drugs and could be involved in MDR. The substrate specificity of the other family members remains to be defined. Specific monoclonal antibodies are required for wide-scale studies on the putative contribution of these closely related transporter proteins to MDR. In this report, we describe the extensive characterization of a panel of monoclonal antibodies (Mabs) detecting several MDR-related transporter proteins in both human and animal tissues. The panel consists of P3II-1 and P3II-26 for MDR3 P-gp; MRPr1, MRPm6, MRPm5, and MIB6 for MRP1; M2I-4, M2II-12, M2III-5 and M2III-6 for MRP2; M3II-9 and M3II-21 for MRP3; and M5I-1 and M5II-54 for MRP5. All Mabs in the panel appeared to be fully specific for their cognate antigens, both in Western blots and cytospin preparations, as revealed by lack of cross-reactivity with any of the other family members. Indeed, all Mabs were very effective in detecting their respective antigens in cytospins of transfected cell lines, whereas in flow cytometric and immunohistochemical analyses, distinct differences in reactivity and suitability were noted. These Mabs should become valuable tools in studying the physiological functions of these transporter proteins, in screening procedures for the absence of these proteins in hereditary metabolic (liver) diseases, and in studying the possible contributions of these molecules to MDR in cancer patients.
Rigid Contact Lens Design: Effects of Overall Diameter Changes on Tear Pump Efficiency (1991)

The effects of rigid contact lens overall diameter changes on tear pump efficiency were studied for lenses of 7 overall diameters (8.2 to 10.0 mm in 0.3-mm steps) while maintaining all other parameters (including a 7.4-mm optic zone diameter) constant. Oxygen uptake rates were measured in the normal, open eye and after static (without blinking) and dynamic (with blinking once every 5 s) wear of oxygen-impermeable (polymethyl methacrylate) contact lenses. Differences between uptake rates obtained under static vs. dynamic conditions served as an index of tear pump efficiency for each lens. Tear pump efficiency increased with the use of progressively smaller lens diameters and subjects with large palpebral aperture sizes were also found to have better tear exchange (r = 0.934, p = 0.006 for the 9.1-mm overall diameter reference lens).
5-Halobenzothiophene Analogues of Melatonin: Synthesis and Affinity for mt&lt;SUB&gt;1&lt;/SUB&gt; and MT&lt;SUB&gt;2&lt;/SUB&gt; Receptors in Man (2000)

A novel series of melatonin analogues based on the benzothiophene nucleus is described. In these compounds the methoxy group was replaced by electron-attracting groups such halogens (Br and Cl) with the aim of supplementing structure-affinity relationships on melatoninergic ligands. Target derivatives were prepared from the corresponding 4-halo-thiophenol. Some of these derivatives had high affinity for mt1 and MT2 receptors, almost as high as that of melatonin.



These results prove that the methoxy group is not an essential requirement for binding to melatoninergic receptors.
Targeted Antimicrobial Therapy Against Streptococcus mutans Establishes Protective Non‐cariogenic Oral Biofilms and Reduces Subsequent Infection (2010)

S. mutans infection is reduced by the presence of existing biofilms. Thus maintaining a healthy or "normal" biofilm through targeted antimicrobial therapy (such as the STAMPs) could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.