gebhart/patrepeval huggingface dataset:
Phosphorylation by Cyclin C/Cyclin-Dependent Kinase 2 following Mitogenic Stimulation of Murine Fibroblasts Inhibits Transcriptional Activity of LSF during G 1 Progression (2009)

Transcription factor LSF is required for progression from quiescence through the cell cycle, regulating thymidylate synthase (Tyms) expression at the G(1)/S boundary. Given the constant level of LSF protein from G(0) through S, we investigated whether LSF is regulated by phosphorylation in G(1). In vitro, LSF is phosphorylated by cyclin E/cyclin-dependent kinase 2 (CDK2), cyclin C/CDK2, and cyclin C/CDK3, predominantly on S309. Phosphorylation of LSF on S309 is maximal 1 to 2 h after mitogenic stimulation of quiescent mouse fibroblasts. This phosphorylation is mediated by cyclin C-dependent kinases, as shown by coimmunoprecipitation of LSF and cyclin C in early G(1) and by abrogation of LSF S309 phosphorylation upon suppression of cyclin C with short interfering RNA. Although mouse fibroblasts lack functional CDK3 (the partner of cyclin C in early G(1) in human cells), CDK2 compensates for this absence. By transient transfection assays, phosphorylation at S309, mediated by cyclin C overexpression, inhibits LSF transactivation. Moreover, overexpression of cyclin C and CDK3 inhibits induction of endogenous Tyms expression at the G(1)/S transition. These results identify LSF as only the second known target (in addition to pRb) of cyclin C/CDK activity during progression from quiescence to early G(1). Unexpectedly, this phosphorylation prevents induction of LSF target genes until late G(1).
Human cytomegalovirus tropism for endothelial/epithelial cells: scientific background and clinical implications (2010)

Human cytomegalovirus (HCMV) has been routinely isolated from and propagated in vitro in human embryonic lung fibroblast (HELF) cell cultures, while in vivo it is known to infect predominantly endothelial and epithelial cells. In recent years, genetic determinants of the HCMV tropism for endothelial/epithelial cells were identified in the UL131A/UL130/UL128 locus of HCMV genome of wild-type strains. UL131A-UL128 gene products form a complex with glycoprotein H (gH) and L (gL) resulting in a gH/gL/UL131A-UL128 complex that is required for HCMV entry into endothelial/epithelial cells. In contrast, virus entry into fibroblasts has its genetic determinants in the complex gH/gL/gO (or gH/gL). During primary HCMV infection, the neutralising antibody response measured in endothelial cells (EC) is potent, occurs very early and is directed mostly against combinations of two or three gene products of the UL131A-128 locus. On the contrary, neutralising antibodies measured in fibroblasts appear late, are relatively weak in potency and are directed against gH and gB. The T-cell immune response to UL131A-UL128 gene products remains to be investigated. Recently, a role has been proposed for neutralising antibody in conferring prevention/protection against HCMV infection/disease in pregnant women with primary HCMV infection. However, the level of cooperation between humoral immunity and the well-established T-cell protection remains to be defined.
Learning to Rank for Information Retrieval (2009)

Learning to rank for Information Retrieval (IR) is a task to automatically construct a ranking model using training data, such that the model can sort new objects according to their degrees of relevance, preference, or importance. Many IR problems are by nature ranking problems, and many IR technologies can be potentially enhanced by using learning-to-rank techniques. The objective of this tutorial is to give an introduction to this research direction. Specifically, the existing learning-to-rank algorithms are reviewed and categorized into three approaches: the pointwise, pairwise, and listwise approaches. The advantages and disadvantages with each approach are analyzed, and the relationships between the loss functions used in these approaches and IR evaluation measures are discussed. Then the empirical evaluations on typical learning-to-rank methods are shown, with the LETOR collection as a benchmark dataset, which seems to suggest that the listwise approach be the most effective one among all the approaches. After that, a statistical ranking theory is introduced, which can describe different learning-to-rank algorithms, and be used to analyze their query-level generalization abilities. At the end of the tutorial, we provide a summary and discuss potential future work on learning to rank.
Biosynthesis of 3-O-sulfated heparan sulfate: unique substrate specificity of heparan sulfate 3-O-sulfotransferase isoform 5 (2003)

Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine to generate 3-O-sulfated heparan sulfate (HS), which is a rare component in HS from natural sources. We previously reported that 3-O- sulfotransferase isoform 5 (3-OST-5) generates both an antithrombin-binding site to exhibit anticoagulant activity and a binding site for herpes simplex virus 1 glycoprotein D to serve as an entry receptor for herpes simplex virus. In this study, we characterize the substrate specificity of 3-OST-5 using the purified enzyme. The enzyme was expressed in insect cells using the baculovirus expression approach and was purified by using heparin-Sepharose and 3',5'-ADP- agarose chromatographies. As expected, the purified enzyme generates both an antithrombin binding site and a glycoprotein D binding site. We isolated IdoUA-AnMan3S and IdoUA-AnMan3S6S from nitrous acid-degraded 3-OST-5-modified HS (pH 1.5), suggesting that 3-OST-5 enzyme sulfates the glucosamine residue that is linked to an iduronic acid residue at the nonreducing end. We also isolated a disaccharide with a structure of DeltaUA2S-GlcNS3S and a tetrasaccharide with a structure of DeltaUA2S-GlcNS-IdoUA2S-GlcNH23S6S from heparin lyases-digested 3-OST-5-modified HS. Our results suggest that 3-OST-5 enzyme sulfates both N-sulfated glucosamine and N-unsubstituted glucosamine residues. Taken together, the results indicate that 3-OST-5 has broader substrate specificity than those of 3-OST-1 and 3-OST-3. The unique substrate specificity of 3-OST-5 serves as an additional tool to study the mechanism for the biosynthesis of biologically active HS.
Effects of Oxidative Stress in Trabecular Meshwork Cells Are Reduced by Prostaglandin Analogues (2008)

Oxidative stress is able to induce characteristic glaucomatous TM changes in vitro, and these oxidative stress-induced TM changes can be minimized by the use of prostaglandin analogues. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.
Crystal Structure of a Novel Dimeric Form of NS5A Domain I Protein from Hepatitis C Virus (2009)

A new protein expression vector design utilizing an N-terminal six-histidine tag and tobacco etch virus protease cleavage site upstream of the hepatitis C virus NS5A sequence has resulted in a more straightforward purification method and improved yields of purified NS5A domain I protein. High-resolution diffracting crystals of NS5A domain I (amino acids 33 to 202) [NS5A(33-202)] were obtained by using detergent additive crystallization screens, leading to the structure of a homodimer which is organized differently from that published previously (T. L. Tellinghuisen, J. Marcotrigiano, and C. M. Rice, Nature 435:374-379, 2005) yet is consistent with a membrane association model for NS5A. The monomer-monomer interface of NS5A(33-202) features an extensive buried surface area involving the most-highly conserved face of each monomer. The two alternate structural forms of domain I now available may be indicative of the multiple roles emerging for NS5A in viral RNA replication and viral particle assembly.
Extremely Superhydrophobic Surfaces with Micro- and Nanostructures Fabricated by Copper Catalytic Etching (2010)

We demonstrate a simple method for the fabrication of rough silicon surfaces with micro- and nanostructures, which exhibited superhydrophobic behaviors. Hierarchically rough silicon surfaces were prepared by copper (Cu)-assisted chemical etching process where Cu nanoparticles having particle size of 10-30 nm were deposited on silicon surface, depending on the period of time of electroless Cu plating. Surface roughness was controlled by both the size of Cu nanoparticles and etching conditions. As-synthesized rough silicon surfaces showed water contact angles ranging from 93° to 149°. Moreover, the hierarchically rough silicon surfaces were chemically modified by spin-coating of a thin layer of Teflon precursor with low surface energy. And thus it exhibited nonsticky and enhanced hydrophobic properties with extremely high contact angle of nearly 180°.
Sirtuin‐mediated deacetylation pathway stabilizes Werner syndrome protein (2008)

Caloric restriction (CR) is known to promote longevity in various species. Sirtuin-mediated deacetylation has been shown to be related to the promotion of longevity in some species. Here, we show that CR of rats led to an increase in the level of Werner syndrome protein (WRN), a recognized DNA repair protein. In addition, CR simultaneously increased the level of SIRT1, a mammalian sirtuin. In HEK293T cells, sirtuin inhibitors decreased the WRN level, and this effect was suppressed by proteasomal inhibitors. Furthermore, we found a decrease in the WRN level in Sirt1-deficient mice. These results indicate that sirtuin-mediated deacetylation stabilizes WRN. STRUCTURED SUMMARY:
Two-Dimensional Electrochromatography/Capillary Electrophoresis on a Microchip (2001)

A two-dimensional separation system on a microfabricated device was demonstrated using open-channel electrochromatography as the first dimension and capillary electrophoresis as the second dimension. The first dimension was operated under isocratic conditions, and the effluent from the first dimension was repetitively injected into the second dimension every few seconds. A 25-cm separation channel with spiral geometry for open-channel electrochromatography was chemically modified with octadecylsilane and coupled to a 1.2-cm straight separation channel for capillary electrophoresis. Fluorescently labeled products from tryptic digests of beta-casein were analyzed in 13 min with this system.
The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. (1995)

The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound.
Prosthesis-guided training of pattern recognition-controlled myoelectric prosthesis (2012)

Pattern recognition can provide intuitive control of myoelectric prostheses. Currently, screen-guided training (SGT), in which individuals perform specific muscle contractions in sync with prompts displayed on a screen, is the common method of collecting the electromyography (EMG) data necessary to train a pattern recognition classifier. Prosthesis-guided training (PGT) is a new data collection method that requires no additional hardware and allows the individuals to keep their focus on the prosthesis itself. The movement of the prosthesis provides the cues of when to perform the muscle contractions. This study compared the training data obtained from SGT and PGT and evaluated user performance after training pattern recognition classifiers with each method. Although the inclusion of transient EMG signal in PGT data led to decreased accuracy of the classifier, subjects completed a performance task faster than when compared to using a classifier built from SGT data. This may indicate that training data collected using PGT that includes both steady state and transient EMG signals generates a classifier that more accurately reflects muscle activity during real-time use of a pattern recognition-controlled myoelectric prosthesis.
Peanut Roots as a Source of Resveratrol (2002)

A potent antioxidant, resveratrol (3,4‘,5-trihydroxystilbene), was extracted using 80% methanol from peanut roots (Arachis hypogaea L.), isolated with a solid-phase extraction column, purified by a semipreparative HPLC, and identified with 1H NMR and MS. The highest and lowest resveratrol contents in the peanut roots of 2000 fall and 2001 spring crops were 1.330 and 0.130 mg/g and 0.063 and 0.015 mg/g, respectively. When the dehydrated peanut root powders of spring and fall crops were combined and cooked with pork-fat patties (1%, w/w) and the separated oils were stored at 60 °C for conjugated diene hydroperoxide (CDHP) determination, CDHP contents of the control oils increased after 3 days of storage, whereas the contents in the peanut root-treated oils of spring and fall crops did not increase after 9 and 15 days of storage, respectively. It is of merit to find that peanut roots, usually left in the field as agricultural waste, contain resveratrol and bear potent antioxidative activity. Keywords: Resveratrol; peanut; peanut root; 3,4‘,5-trihydroxystilbene; antioxidant
Characterization of Uveoscleral Outflow in Enucleated Porcine Eyes Perfused under Constant Pressure (2004)

The results suggest that choroidal drainage into the vortex veins is insignificant in the absence of blood perfusion. No significant washout effects in porcine eyes were observed.
The in vitro growth response of primary human colorectal and gastric cancer cells to gastrin (1989)

A series of 31 colorectal and 13 gastric primary human tumours were screened for their growth response to human gastrin-17 in vitro, as assessed by 75Se-seleno-methionine incorporation. Fifty-five percent of colorectal and 69% of gastric tumours showed a significant trophic response to the hormone. The responses were achieved at physiological gastrin concentrations (post-prandial circulating gastrin levels) in 35% of colorectal and 55% of gastric tumours. Lymphocytes from tumour-associated lymph nodes showed no response to the hormone and "normal" mucosal cells (obtained from the resection margin of the surgical specimen) showed lower mean levels of 75Se-seleno-methionine uptake (colorectal: 110%; gastric: 119%, expressed as a percentage of the control) when compared to tumours (colorectal: 151%; gastric: 147%). The small number of well differentiated and/or Dukes' stage A colorectal tumours examined were gastrin-responsive, but all the responsive gastric tumours were poorly differentiated. With respect to ploidy, 89% of diploid and 67% of aneuploid colorectal tumours responded trophically to gastrin. Patients with colorectal or gastric tumours may benefit from treatment with gastrin antagonists.
Cover Image, Volume 117, Number 8, August 2016 (2016)

Cover: The cover image, by Nicholas P. Greene et al., is based on the Article microRNA-16 Is Downregulated During Insulin Resistance and Controls Skeletal Muscle Protein Accretion, DOI: 10.1002/jcb.25476.
All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. (1981)

In hypotrichous ciliates, all of the macronuclear DNA is in the form of low molecular weight molecules with an average size of approximately 2200 base pairs. Total macronuclear DNA from four hypotrichs has been shown to have inverted terminal repeats by direct sequence analysis. In Oxytricha nova, Oxytricha sp., and Stylonychia pustulata, this terminal sequence may be written as 5'-C4A4C4A4C4 ... 3'-G4T4G4T4G4T4G4T4G4 ... In Euplotes aediculatus, the sequences is similar but differs in the lengths of the duplex region (28 base pairs) and of the putative 3' extension (14 base pairs). Also in Euplotes, a second common sequence of 5 base pairs (A-A-C-T-T-T-T-G-A-A) occurs internal to the terminal repeat and a 17-base-pair heterogeneous region: 5'-C4A4C4A4C4A4C4(X)17T-T-G-A-A ... 3'-G2T4G4T4G4T4G4T4G4T4G4(X)17A-A-C-T-T ... The length of the terminal repeat sequence for O. nova was confirmed in cloned macronuclear DNA molecules.
Identification of a cytidine-specific ribonuclease from chicken liver. (1980)

Rapid RNA sequencing technology was used to determine if the base specificities of an RNase recently purified from chicken liver would prove useful for RNA sequence analysis. Escherichia coli 5 S [5'-32P]rRNA or yeast 5.8 S [5'-32P]rRNA was digested with the enzyme and this digest, along with digests derived from RNases of known specificity (U2, T1, T2) were subjected to electrophoresis through denaturing polyacrylamide slab gels. Following autoradiography, the banding patterns arising from the activity of each enzyme were compared, and the base specificity of the unknown RNase was established. The chicken liver RNase was found to have a marked preference for phosphodiester bonds containing cytidylic acid residues, a property which should make the enzyme useful for distinguishing between pyrimidines in RNA sequencing.
Late-breaking abstract: Inhaled calcium based dry powder inhibits rhinovirus-induced inflammation and exacerbation in a mouse model of allergic airway inflammation (2011)

Acute exacerbations (AE) in asthma are associated with rhinovirus (Rv) infection. AEs drive disease progression and cause loss of lung function, yet no current therapies target this infectious component. Calcium (Ca) based dry powder (DP) formulations were developed as host-targeted therapies that broadly reduce viral infection in vitro , including Rv. Here, a lead Ca-based DP (PUR118) was tested for efficacy against Rv in a mouse model of infection and AE using Rv1B infection in naïve and ovalbumin (OVA)-challenged mice (Bartlett NW et al Nat Med 2008). Mice (Balb/c) were treated with PUR118 or control DP by whole body exposure, twice daily (BID) 2d prior to Rv infection (5×10 6 TCID50) and BID on day of infection. Bronchoalveolar lavage (BAL) inflammation was evaluated 24h post-infection. Additional indices of infection and exacerbation included: viral titers, and expression of relevant cytokines and chemokines. Rv infection caused significant neutrophilic inflammation in naïve mice (7.5×10 5 BAL neutrophils/ml) and exacerbated inflammation in OVA challenged mice (44% increase over control) with increased neutrophils, cytokines and chemokines. In naïve mice, PUR118 treatment reduced neutrophilic inflammation by 38%, which correlated with reduced cytokine and chemokine expression. Similar results were observed in OVA mice where PUR118 treatment reduced neutrophilic inflammation by 40%. The data show Ca-based DP significantly inhibits Rv-induced airway inflammation and Rv-driven exacerbation responses in an asthma-like mouse model. These data support the development of inhaled Ca-based DP to treat infectious causes of AEs in respiratory disease.
A Rational Approach to the Design and Synthesis of a New Bradykinin B1 Receptor Antagonist (2000)

We have previously synthesized a potent and selective B(1) bradykinin receptor antagonist, JMV1645 (H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH), containing a dipeptide mimetic ((3S)-amino-5-carbonylmethyl-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety) at the C-terminal. Analogues of this potent B(1) bradykinin receptor antagonist in which the central Pro(2)-Hyp(3)-Gly(4)-Igl(5) tetrapeptide has been replaced by constrained N-1-substituted-1,3,8-triazaspiro¿4. 5decan-4-one ring system were synthesized. Among these analogues, compound JMV1640 (1) was found to have an affinity of 24.10 +/- 9.48 nM for the human cloned B(1) receptor. It antagonized the ¿des-Arg(10)-kallidin-induced contraction of the human umbilical vein (pA(2) = 6.1 +/- 0.1). Compound 1 was devoid of agonist activity at the kinin B(1) receptor. Moreover, it did not bind to the human cloned B(2) receptor. Therefore, JMV1640 constitutes a lead compound for the rational search of nonpeptide B(1) receptor analogues based on the BK sequence.
Central venous catheter infusions: A laboratory model shows large differences in drug delivery dynamics related to catheter dead volume * (2007)

Objective: Central venous catheters (CVCs) are conduits for drug infusions. Dead volumes of different CVC lumens vary considerably. This study quantitatively evaluated drug delivery dynamics of CVCs in a laboratory model of continuous drug infusion. Design: CVCs studied included a triple-lumen catheter (16-gauge and 18-gauge lumens), the proximal infusion port of a pulmonary artery catheter, and a 9-Fr introducer sheath, with and without a pulmonary artery catheter in the lumen. One syringe pump infused a carrier. A second pump infused the model drug methylene blue (3 mL/hr), joining the carrier immediately upstream of the CVC. Samples were collected every minute for quantitative analysis. Setting: Laboratory model. Subjects: None. Interventions: At low fixed flow rates, experiments characterized drug delivery kinetics of different CVCs. Data collection then assessed effects of increased carrier flow. Measurement and Main Results: The time to steady-state delivery after initiation of methylene blue infusion differed between CVCs. At a carrier flow of 10 mL/hr, the fastest achievement of steady-state delivery was with the 18-gauge lumen of a triple-lumen catheter. The 9-Fr introducer had the slowest time to achieve steady-state delivery. Other CVCs had intermediate kinetics. Reducing drug delivery from steady state to zero after cessation of methylene blue infusion was fastest with the 18-gauge lumen and slowest with the 9-Fr introducer. Increasing carrier flow rates from 10 to 60 mL/hr hastened the time to target for initiation and cessation of methylene blue delivery. Conclusions: Experiments demonstrate large differences between CVCs in the dynamics for delivery of model drug methylene blue. Achieving targeted steady-state delivery, and termination of a planned continuous drug infusion, may be far slower than typically appreciated. Delivery kinetics depend on the dead volume and the rate of carrier flow. Safe and effective management of continuous drug infusions depends on understanding the dynamics of the delivery system.
The distributions, mechanisms, and structures of metabolite-binding riboswitches (2007)

Riboswitches are vital components of many genomes. The additional riboswitch variants and updated aptamer structure models reported here will improve future efforts to annotate these widespread regulatory RNAs in genomic sequences and inform ongoing structural biology efforts. There remain significant questions about what physiological and evolutionary forces influence the distributions and mechanisms of riboswitches and about what forms of regulation substitute for riboswitches that appear to be missing in certain lineages.