gebhart/patrepeval huggingface dataset:
Identification and Characterization of a Novel Serine-Arginine-Rich Splicing Regulatory Protein (2000)

We have identified an 86-kDa protein containing a single amino-terminal RNA recognition motif and two carboxy-terminal domains rich in serine-arginine (SR) dipeptides. Despite structural similarity to members of the SR protein family, p86 is clearly unique. It is not found in standard SR protein preparations, does not precipitate in the presence of high magnesium concentrations, is not recognized by antibodies specific for SR proteins, and cannot complement splicing-defective S100 extracts. However, we have found that p86 can inhibit the ability of purified SR proteins to activate splicing in S100 extracts and can even inhibit the in vitro and in vivo activation of specific splice sites by a subset of SR proteins, including ASF/SF2, SC35, and SRp55. In contrast, p86 activates splicing in the presence of SRp20. Thus, it appears that pairwise combination of p86 with specific SR proteins leads to altered splicing efficiency and differential splice site selection. In all cases, such regulation requires the presence of the two RS domains and a unique intervening EK-rich region, which appear to mediate direct protein-protein contact between these family members. Full-length p86, but not a mutant lacking the RS-EK-RS domains, was found to preferentially interact with itself, SRp20, ASF/SF2, SRp55, and, to a slightly lesser extent, SC35. Because of the primary sequence and unique properties of p86, we have named this protein SRrp86 for SR-related protein of 86 kDa.
Comparison of physicochemical properties of purified mucus glycoproteins isolated from respiratory secretions of cystic fibrosis and asthmatic patients (1985)

The major nonreduced mucus glycoproteins (mucins) from sputa of cystic fibrosis (CF) and asthmatic patients have been purified to electrophoretic homogeneity and subjected to physical and chemical characterization. The sputum specimens were solubilized in buffer containing 0.22 M KSCN and fractionated on Bio-Gel A-5m, followed by digestion with DNase, rechromatography on the same column, and chromatography on hydroxylapatite. Sodium dodecyl sulfate gel electrophoresis of purified mucins gave a single band. Carbohydrate analyses of the purified mucins showed no significant differences in the sugar components from the two mucins. However, the CF mucin contained substantially higher (11%) sulfate content than that observed for the asthmatic mucin (5.9%). Amino acid analyses indicated that the CF mucin had higher levels of serine plus threonine (35%) as compared to the asthmatic mucin (29%). In contrast, CF mucin contained a lower content of aspartate, glutamate, and glycine than that observed for the asthmatic mucin. Molecular weights of 3.8 X 10(6) and 3.5 X 10(6) were obtained for CF and asthmatic mucins, respectively, from light-scattering studies of mucins in the presence of 6 M guanidine hydrochloride. Reduction of the disulfide bonds of the two mucins did not alter their molecular weights. Liquid chromatographic studies on Sepharose CL2B showed that CF mucin forms aggregates sufficiently large to be excluded from the gel. As compared to the CF mucin, the asthmatic mucin formed fewer of these large aggregates under identical experimental conditions. Reduction and alkylation of the mucins resulted in their inability to form aggregates. The higher state of aggregation of CF mucin may influence the viscoelastic properties of the CF lung's mucus secretions.
A SINGLE INTRA-ARTICULAR INJECTION OF LIPOSOMALLY CONJUGATED METHOTREXATE SUPPRESSES JOINT INFLAMMATION IN RAT ANTIGEN-INDUCED ARTHRITIS (1996)

In this study, we sought to determine whether liposomal preparations containing a phospholipid conjugate of methotrexate and dimyristoylphosphatidylethanolamine (MTX-gamma-DMPE) incorporated within their lipid membranes are effective in suppressing established joint inflammation in a monoarticular model of arthritis in the rat. Arthritis was induced in the right knee joint of Lewis rats. The rats were treated with a single intra-articular injection of either free methotrexate (MTX), liposomal MTX [MTX-multilamellar vesicles (MLV)-1.2 microns or MTX-small unilamellar vesicles (SUV)-100 nm], control liposomes (E-LIPO) or saline into the inflamed knee 7 days after arthritis induction. There was no significant difference in knee swelling in MTX-, saline- and E-LIPO-treated rats up to 21 days after treatment. However, MTX-MLV treatment produced a significant reduction in knee swelling (26.5 +/- 6.0%: mean +/- S.E.M.) 1 day after intra-articular injection compared with MTX (3.5 +/- 3.5%) and MTX-SUV (14.4 +/- 2.4%), respectively. Over the next 20 days, knee swelling in MTX-MLV-treated rats fell progressively and almost returned to normal. MTX-MLV treatment also inhibited the cellular infiltration associated with the arthritis. Large multilamellar liposomal preparations of MTX-gamma-DMPE are more effective than free MTX and MTX-SUV in suppressing inflammation. Their differential effects in treating the antigen-induced arthritis model are related to their retention within the joint space.
Multiple fluorescence labeling with europium chelators. Application to time-resolved fluoroimmunoassays (1989)

Multiple fluorescence labeling with conventional probes like fluorescein, to improve the detection limit of labeled reactants, is not usually successful because of fluorescence quenching. In contrast, we found that the europium chelator 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA) can be incorporated into proteins at very high molar ratios. Working with thyroglobulin as a model protein, we found that when 160 BCPDA molecules are incorporated into one thyroglobulin molecule, the fluorescence emitted by the labeled protein in the presence of excess Eu3+, is equivalent to that emitted by approximately 900 molecules of unconjugated BCPDA:Eu3+ complexes. We took advantage of the lack of any quenching effects and of the enhancement observed with the multiply labeled protein, to develop a universal reagent system consisting of (a) streptavidin covalently coupled to BCPDA labeled thyroglobulin and (b) excess Eu3+. With this approach, streptavidin is heavily labeled through thyroglobulin and retains its full biotin binding activity. We used the reagent to develop a highly sensitive time-resolved heterogeneous immunofluorometric assay of alpha-fetoprotein (AFP) in serum, using monoclonal antibodies. One antibody is immobilized in white microtitration wells (solid-phase) and the other is biotinylated. We demonstrate that this assay, using the newly developed reagent, is 25-fold more sensitive than the one using directly BCPDA labeled antibody and 5-fold more sensitive than an assay that uses BCPDA-labeled streptavidin. The detection limit of the assay with the new reagent was down to 60 amol of AFP per well. We conclude that multiple fluorescence labeling with europium chelators is an effective method of extending the sensitivity of currently used fluorescence immunoassay procedures.
Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo (2003)

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.
Identification of Genes Involved in Repair of DNA Double-Strand Breaks in Mammalian Cells (1998)

At least two mechanisms of DNA double-strand break (DSB) repair operate in mammalian cells. Homologous recombination, which plays a major role in lower organisms, plays a less significant role in higher organisms. In contrast, the majority of DSBs in mammalian cells are rejoined by a mechanism, termed non-homologous end joining (NHEJ), that does not depend upon extensive regions of homology. This process is also used to rejoin site-specific DSBs introduced during V(D)J recombination. From the analysis of defective rodent mutants, four proteins (Ku70, Ku80, DNA-PKcs and Xrcc4) that function in this process in mammalian cells have been identified. DNA ligase IV is also strongly implicated since it associates strongly with XRCC4, and since DNA ligase IV-deficient yeast are defective in their ability to carry out NHEJ. In S. cerevisiae, Sir2p, Sir3p and Sir4p, three proteins required for transcriptional silencing, are also required for NHEJ. Additionally, the yeast mutants, xrs2, rad50 and mre11, which are defective in meiotic recombination, are also defective in NHEJ. Here I review the evidence implicating these proteins as functioning in NHEJ and discuss their properties and role in other pathways. The significance of DSB repair to clinical radiosensitivity and human disorders is also evaluated.
An Efficient and Diastereoselective Synthesis of PSI-6130: A Clinically Efficacious Inhibitor of HCV NS5B Polymerase (2009)

R7128 is the prodrug of 2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected d-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution on a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates.
Quantitative Analysis of Control Flow Checking Mechanisms for Soft Errors (2014)

Control Flow Checking (CFC) based techniques have gained a reputation of providing effective, yet low-overhead protection from soft errors. The basic idea is that if the control flow -- or the sequence of instructions that are executed -- is correct, then most probably the execution of the program is correct. Although researchers claim the effectiveness of the proposed CFC techniques, we argue that their evaluation has been inadequate and can even be wrong! Recently, the metric of vulnerability has been proposed to quantify the susceptibility of computation to soft errors. Laced with this comprehensive metric, we quantitatively evaluate the effectiveness of several existing CFC schemes, and obtain surprising results. Our results show that existing CFC techniques are not only ineffective in protecting computation from soft errors, but that they incur additional power and performance overheads. Software-only CFC protection schemes (CFCSS [14], CFCSS+NA [2], and CEDA [18]) increase system vulnerability by 18% to 21% with 17% to 38% performance overhead; Hybrid CFC protection technique, CFEDC [4] also increases the vulnerability by 5%; While the vulnerability remains almost the same for hardware only CFC protection technique, CFCET [15], they cause overheads of design cost, area, and power due to the hardware modifications required for their implementations.
Bioactive and nuclease-resistant l -DNA ligand of vasopressin (1997)

In vitro selection experiments have produced nucleic acid ligands (aptamers) that bind tightly and specifically to a great variety of target biomolecules. The utility of aptamers is often limited by their vulnerability to nucleases present in biological materials. One way to circumvent this problem is to select an aptamer that binds the enantiomer of the target, then synthesize the enantiomer of the aptamer as a nuclease-insensitive ligand of the normal target. We have so identified a mirror-image single-stranded DNA that binds the peptide hormone vasopressin and have demonstrated its stability to nucleases and its bioactivity as a vasopressin antagonist in cell culture.
Purification and Characterization of a Maltotetraose-Forming Alkaline (alpha)-Amylase from an Alkalophilic Bacillus Strain, GM8901 (1995)

An alkalophilic bacterium, Bacillus sp. strain GM8901, grown at pH 10.5 and 50(deg)C, produced five alkaline amylases in culture broth. At an early stage of the bacterial growth, amylase I (Amyl I) was produced initially and then, as cultivation progressed, four alkaline amylases, Amyl II, Amyl III, Amyl IV, and Amyl V, were produced from proteolytic degradation of Amyl I. A serine protease present in the culture medium was believed to be involved in Amyl I degradation. We purified Amyl I from the culture supernatant by ammonium sulfate precipitation, heparin-Sepharose CL-6B column chromatography, phenyl-Toyopearl column chromatography, and Mono Q HR5/5 high-performance liquid chromatography. The molecular weight of Amyl I was estimated to be about 97,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amyl I had an extremely high optimal pH of 11.0 to 12.0 and was stable in a broad pH range of 6.0 to 13.0. Amyl I had an optimal temperature of 60(deg)C and was stable up to 50(deg)C. Thermostability was increased in the presence of Ca(sup2+) and soluble starch. The enzyme required metal ions such as Ca(sup2+), Mg(sup2+), Cu(sup2+), Co(sup2+), Ag(sup+), Zn(sup2+), and Fe(sup2+) for its enzyme activity and was inhibited by 1 mM EDTA and 1 mM phenylmethylsulfonyl fluoride. According to the mode of action of Amyl I on starch, Amyl I was classified as an (alpha)- and exo-amylase. Amyl I produced maltotetraose predominantly from starch via intermediates such as maltohexaose and maltopentaose.
Detecting the number of clusters of individuals using the software structure: a simulation study (2005)

The identification of genetically homogeneous groups of individuals is a long standing issue in population genetics. A recent Bayesian algorithm implemented in the software STRUCTURE allows the identification of such groups. However, the ability of this algorithm to detect the true number of clusters (K) in a sample of individuals when patterns of dispersal among populations are not homogeneous has not been tested. The goal of this study is to carry out such tests, using various dispersal scenarios from data generated with an individual-based model. We found that in most cases the estimated 'log probability of data' does not provide a correct estimation of the number of clusters, K. However, using an ad hoc statistic DeltaK based on the rate of change in the log probability of data between successive K values, we found that STRUCTURE accurately detects the uppermost hierarchical level of structure for the scenarios we tested. As might be expected, the results are sensitive to the type of genetic marker used (AFLP vs. microsatellite), the number of loci scored, the number of populations sampled, and the number of individuals typed in each sample.
Evaluation of antemortem polymerase chain reaction and serologic methods for detection of Lawsonia intracellularis-exposed pigs (1998)

Not all animals that are infected with L intracellularis shed the organism in feces at detectable amounts.
Frequency-Independent Phase Noise in a Dual-Wavelength Brillouin Fiber Laser (2011)

An in-depth analysis of the phase noise of a microwave oscillator based on dual-wavelength stimulated Brillouin scattering is presented. The system is investigated under the influence of injection-locking and also in a regenerative-frequency configuration. Measurements from 1 to 25 GHz demonstrate the invariance of the phase-noise spectrum with respect to carrier frequency. Phase noise of -90 dBc/Hz at 1-kHz offset is shown, and is compared to the best reported performance of optical heterodyne sources. The frequency stability of the oscillator is also discussed.
Micromachined pre-focused 1×Nflow switches for continuous sample injection (2001)

In this paper, we present an investigation of a microfluidic chip capable of continuous sample switching and injection for bio-analytical applications. The novel device integrates two important microfluidic phenomena, including hydrodynamic focusing and valveless flow switching inside multi-ported microchannels. In this study, a simple theoretical model based on the `flow-rate-ratio' method is first proposed to predict the performance of the device. Based on these data, a pre-focused 1×N flow switch is designed and fabricated using micromachining techniques. A novel micromachining technique is demonstrated which combines quartz template fabrication and replication of microstructures on polymethylmethacrylate (PMMA) substrates for mass production of microfluidic devices. Three-dimensional templates with an inverse image of microfluidic channels are fabricated on quartz substrates and then used to imprint microstructures onto PMMA substrates using hot embossing methods. Finally, the flow switching is verified experimentally with the use of microscopic visualization of water sheath flows and a dye-containing sample flow. The experimental data indicate that the sample flow could be hydrodynamically pre-focused to a narrow stream and then guided into a desired outlet port based on relative sheath and sample flow rates. It also shows that the added `pre-focusing' function prior to the flow switching is crucial for precise sample injection. The microfluidic chip could be applied in the fields of bio/chemical analysis.
Performance evaluation of a wearable inertial motion capture system for capturing physical exposures during manual material handling tasks (2012)

Use of an inertial motion capture system can advance the quantification of physical exposures in situ. Results indicate a good potential capacity for capturing physical exposure data in the field for an extended period, while highlighting potential limitations. Future system application can help provide better understandings of dose-exposure relationships.
Functional Consequences of the Sustained or Transient Activation by Bax of the Mitochondrial Permeability Transition Pore (1999)

The overexpression of Bax kills cells by a mechanism that depends on induction of the mitochondrial permeability transition (MPT) (Pastorino, J. G., Chen, S.-T., Tafani, M., Snyder, J. W., and Farber, J. L. (1998) J. Biol. Chem. 273, 7770-7775). In the present study, purified, recombinant Bax opened the mitochondrial permeability transition pore (PTP). Depending on its concentration, Bax had two distinct effects. At a concentration of 125 nM, Bax caused the release of the intermembranous proteins cytochrome c and adenylate kinase and the release from the matrix of sequestered calcein, effects prevented by the inhibitor of the PTP cyclosporin A (CSA). At this concentration of Bax, there was no detectable mitochondrial swelling or depolarization. These effects of low Bax concentrations are interpreted as the consequence of transient, non-synchronous activation of the PTP followed by a prompt recovery of mitochondrial integrity. By contrast, Bax concentrations between 250 nM and 1 microM caused a sustained opening of the PTP with consequent persistent mitochondrial swelling and deenergization (the MPT). CSA prevented the MPT induced by Bax. Increasing concentrations of calcium caused a greater proportion of the mitochondria to undergo the MPT in the presence of Bax. Importantly, two known mediators of apoptosis, ceramide and GD3 ganglioside, potentiated the induction by Bax of the MPT. The data imply that Bax mediates the opening of the mitochondrial PTP with the resultant release of cytochrome c from the intermembranous space.
Self-securing storage: protecting data in compromised system (2000)

Self-securing storage prevents intruders from undetectably tampering with or permanently deleting stored data. To accomplish this, self-securing storage devices internally audit all requests and keep old versions of data for a window of time, regardless of the commands received from potentially compromised host operating systems. Within the window, system administrators have this valuable information for intrusion diagnosis and recovery. Our implementation, called S4, combines log-structuring with journal-based metadata to minimize the performance costs of comprehensive versioning. Experiments show that self-securing storage devices can deliver performance that is comparable with conventional storage systems. In addition, analyses indicate that several weeks worth of all versions can reasonably be kept on state-of-the-art disks, especially when differencing and compression technologies are employed.
Improvement in properties of urea by phosphogypsum coating. (2010)

Particle coating is becoming increasingly important in fertilizer, pharmaceutical and food industries. The demand for coating granular fertilizers with minerals is increasing. Urea is coated with PhosphoGypsum, neem oil, polymeric suspensions and micronutrients like sulfer, zinc etc.Coating of PhosphoGypsum on urea fertilizer is a important application of coating process . Coating of urea particles is done to increase nitrogen use efficiency of urea. Nitrogen losses due to leaching, surface volatilization, and denitrification can be minimized by controlling the dissolution rate. Coating also helps to impart strength, increase in bulk density and lowering of caking tendency, thus improving the handling properties. The objective of present paper is to present the improvement in properties of urea obtained by fluidized bed coating of urea with Phosphogypsum using wet and dry methods.Emulsion of PhosphoGypsum, Neem (Azadirachta indica L.) oil, LAB (Linear Alkyl Benzene) and water was prepared in concentrations of 5%, 10% and 15%. Coating experiments were carried out with both PhosphoGypsum, Neem Oil, LAB and water (wet coating) and PhosphoGypsum, Neem Oil and LAB (dry coating) . PhosphoGypsum coated samples were analyzed for crushing strength, dissolution rate, dustiness factor and phosphogypsum content. Characterization of coated and uncoated urea prills is done to optimize and control the process of coating and also the performance of urea coating process can be checked which is useful for checking feasibility of this process on an industrial scale. The experimental results showed that wet method is better than dry method and 1.7 mm diameter size particle give better results than 1.4 mm size diameter particle. Dissolution rate, which is directly related to the nitrogen use efficiency is reduced as a result of coating, thus giving coated urea high moisture holding capacity.
A half-split cylindrical dielectric resonator antenna using slot-coupling (1993)

A half-split cylindrical dielectric resonator placed on a metallic plane and excited in its magnetic dipole mode is a potentially useful antenna element. The use of a microstrip line-slot feed scheme for exciting this antenna is reported. Experimental results show that the antenna displays the anticipated radiation pattern and it has a high operating frequency bandwidth (about 10%). The overall antenna configuration can be easily integrated with MICs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>