gebhart/patrepeval huggingface dataset:
TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand–independent T Helper Cell Activation (1999)

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4(+) T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4(+) T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4(+) T cell responses that produce normal levels of interferon gamma, suggesting a CD40L/CD40-independent mechanism of CD4(+) T cell priming that to date has not been elucidated. Here we show that CD4(+) T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4(+) T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4(+) T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.
The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension (1989)

The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, and hypertriglyceridemia even in the absence of significant overall obesity. This article examines the evidence that upper-body obesity, as usually induced by caloric excess in the presence of androgens, mediates these problems by way of hyperinsulinemia. Because of these interrelationships, there is a need to identify and prevent upper-body obesity or, failing that, to provide therapies that will control the associated problems without aggravating hyperinsulinemia.
Compartmentalization of Chemically Separated Components into Droplets (2009)

Not merely a drop in the ocean: The integration of capillary electrophoresis (CE) with droplet generation driven by electroosmotic flow enabled the compartimentalization of molecular components separated by CE in a series of droplets (see picture; the green bars represent the separated analytes). The droplet-confined bands can be docked and studied on a chip.
An investigation of the efficacy of a polyvalent mastitis vaccine using different vaccination regimens under field conditions in the United Kingdom (2014)

Vaccination can play a useful role in mastitis control programs, although there is a relative dearth of large, well-controlled field efficacy studies. This paper presents the findings on the use of a commercially available vaccine (Startvac, Hipra UK Ltd., Nottingham, UK) on commercial units under UK field conditions. In total, 3,130 cows were recruited from 7 farms and were randomly allocated, within farm, to 1 of 3 groups. The first group received the vaccine following the label regimen, the second group was vaccinated every 90 d following an initial vaccination course, and the third group was left unvaccinated to act as controls. Vaccine efficacy was assessed in the first 120 d of lactation. Data were available for analysis from 1,696 lactations in 1,549 cows. In total, 779 cases of clinical mastitis occurred in the 3 study groups, and we detected no significant difference in the incidence or prevalence of clinical or subclinical mastitis between any of the 3 groups. Mastitis vaccination following the label regimen was associated with a significant reduction in the severity of clinical cases. Cows in this group were at significantly decreased odds of developing clinical mastitis presenting with more than just milk changes [odds ratio: 0.58; 95% confidence interval (CI): 0.35-0.98]. Similarly, each additional vaccination resulted in a cow being at decreased odds of developing clinical mastitis presenting with more than just milk changes (odds ratio: 0.87; 95% CI: 0.77-0.98). Although no cows were culled because of severe mastitis in either of the vaccinated groups, we detected no significant difference in the mastitis-related culling rate between groups. Analysis of milk production data demonstrated that, on average, cows on the label regimen produced a higher volume of milk (231 L; 95% CI: 104.1-357.4) and more milk solids (12.36 kg; 95% CI: 3.12-21.60) than unvaccinated cows in the first 120 d of lactation. Conservative analysis suggested that a return on investment of 2.57:1 could be expected under UK conditions based on increased milk yield alone.
Bit-interleaved coded modulation with iterative decoding and 8 PSK signaling (2002)

We have suggested bit-interleaved coded modulation with soft decision iterative decoding (BICM-ID) for bandwidth-efficient transmission over Gaussian and fading channels. Unlike trellis coded modulation, BICM-ID has a small free Euclidean distance but large diversity order due to bit interleaving. With iterative decoding, soft bit decisions can be employed to significantly improve the conditional intersignal Euclidean distance. This leads to a large coding gain, comparable to that of turbo TCM, over both Gaussian and Rayleigh fading channels with much less system complexity. We address critical design issues to enhance the decoding performance and provide the analytical bounds on the performance with an ideal feedback assumption. We investigate the performance characteristics of BICM-ID through extensive simulations and show that at high signal to noise ratios, the performance of BICM-ID converges to the performance assuming error-free feedback.
Cloning of the Clostridium acetobutylicum ATCC 824 acetyl coenzyme A acetyltransferase (thiolase; EC 2.3.1.9) gene (1991)

Thiolase (acetyl coenzyme A acetyltransferase; EC 2.3.1.9) from Clostridium acetobutylicum is a key enzyme in the production of acids and solvents in this organism. The purification and properties of the enzyme have already been described (D. P. Wiesenborn, F. B. Rudolph, and E.T. Papoutsakis, Appl. Environ. Microbiol. 54:2717-2722, 1988). The thl gene encoding the thiolase has been cloned by using primary antibodies raised to the purified enzyme. A bacteriophage lambda EMBL3 library of C. acetobutylicum DNA was prepared and screened by immunoblots with the antithiolase antibodies. Phage DNA was purified from positive plaques, and restriction enzyme digests identified an approximately 4.8-kb AccI fragment common to all positive plaques. A corresponding fragment was also found in AccI digests of C. acetobutylicum chromosomal DNA. The fragment was purified and EcoRI linkers were attached before being subcloned into pUC19. Maxicell analysis showed the production of an approximately 42-kDa protein, whose size corresponded to the molecular size of the purified thiolase, from the clostridial insert. Enzyme activity assays and Western blot (immunoblot) analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated whole-cell extracts of Escherichia coli harboring the cloned thl confirmed the presence of the thiolase encoded within the cloned DNA.
Basic fibroblast growth factor induces cholangiocarcinoma cell migration via activation of the MEK1/2 pathway (2011)

The purpose of this study was to investigate the roles played by basic fibroblast growth factor (bFGF) in the induction of cholangiocarcinoma cell progression and to identify the signal transduction molecules that are activated by bFGF in cholangiocarcinoma cells. FGF receptor-2 (FGFR2) was shown to be expressed in two cholangiocarcinoma cell lines (RMCCA1 and KKU-100). Samples from RMCCA1 and KKU-100 were assayed for the mRNA. Phosphorylation levels were determined by Western blotting. Treatment of the cholangiocarcinoma cells with bFGF enhanced signaling via the phosphorylation of MEK1/2, induced cholangiocarcinoma cell migration and resulted in high levels of actin polymerization. Moreover, treatment with a MEK1/2 inhibitor (U0126) attenuated the effect of bFGF-induced cholangiocarcinoma cell migration. Taken together, these observations indicate that bFGF enhances the migration of cholangiocarcinoma cells and that this enhancement is regulated by the phosphorylation of MEK1/2.
NMR Studies of Simple Molecules on Metal Surfaces (1986)

In recent years, improvements in the sensitivity of nuclear magnetic resonance have made it possible to detect progressively smaller numbers of nuclei. Experiments and studies previously thought to be impractical can now be undertaken, for example, the study of phenomena at surfaces. Nuclear magnetic resonance has been applied to study simple molecules (carbon monoxide, acetylene, and ethylene) adsorbed on metal surfaces (ruthenium, rhodium, palladium, osmium, iridium, and platinum). The metals, in the form of clusters 10 to 50 angstroms in diameter, supported on alumina, are typical of real catalysts. The experiments provide information about the bonding of the molecules to the metal, the structures the molecules assume after adsorption, the motion of molecules on the surface, the breakup of molecules induced by heating, and the products of such breakup.
Geldanamycin selectively destabilizes and conformationally alters mutated p53. (1995)

Mutated p53 proteins interfere in the function of wild type p53 and may also serve as a dominant oncogene. The vast majority of p53 mutations result in a protein of altered conformation and prolonged half-life. We sought to examine whether geldanamycin, a drug capable of destabilizing several oncogene and proto-oncogene products, could alter the stability and DNA binding characteristics of several mutated p53 proteins. Brief exposure to GA destabilized the p53 protein of several breast, prostate and leukemic cell lines harboring mutated p53 alleles, resulting in a significant reduction in p53 steady state level and half-life. In contrast to its effects on mutated p53, GA altered neither steady state level nor inducibility of the wild type protein. In addition to its effects on protein stability, GA also altered the conformation of mutated p53, so that it was no longer detectable with a mutant conformation-specific antibody. Finally, mutated p53 protein isolated from GA-treated cells regained partial ability to bind a wild type-specific p53 DNA consensus sequence. These data indicate the feasibility of pharmacologic intervention for altering the mutated p53 phenotype.
Requirements for intron-mediated enhancement of gene expression in Arabidopsis (2002)

To explore possible mechanisms of intron-mediated enhancement of gene expression, the features of PAT1 intron 1 required to elevate mRNA accumulation were systematically tested in transgenic Arabidopsis. This intron is remarkably resilient, retaining some ability to increase mRNA accumulation when splicing was prevented by mutation of 5' and 3' splice sites, branchpoint sequences, or when intron U-richness was reduced. Enhancement was abolished by simultaneously eliminating branchpoints and the 5' splice site, structures involved in the first two steps of spliceosome assembly. Although this suggests that the splicing machinery is required, intron splicing is clearly not enough to enhance mRNA accumulation. Five other introns were all efficiently spliced but varied widely in their ability to increase mRNA levels. Furthermore, PAT1 intron 1 was spliced but lost the ability to elevate mRNA accumulation when moved to the 3' UTR. These findings demonstrate that splicing per se is neither necessary nor sufficient for an intron to enhance mRNA accumulation, and suggest a mechanism that requires intron recognition by the splicing machinery but also involves nonconserved intron sequences.
Bridged Bicyclic Cores Containing a 1,1-Diarylethylene Motif Are High-Affinity Subtype-Selective Ligands for the Estrogen Receptor (2003)

The actions of estrogens are mediated through the two estrogen receptors, ERalpha and ERbeta. Compounds that interact selectively with ERalpha or ERbeta are of interest because they could be used to explore the biological roles of these ER subtypes and they might be interesting estrogen pharmaceuticals. In a new approach to develop ER subtype-selective ligands, we have embellished the 1,1-diarylethylene motif, common to many nonsteroidal estrogens, with various bridged bicyclic or tricyclic cores, including ones based on bicyclo[3.3.1]nonane, bicyclo[2.2.1]heptane, and selected bi- and tricyclic terpenoids. This design leads to three-dimensional ER ligands of unusual structure that we have used to probe the size and shape of the ligand binding pocket of ERalpha and ERbeta. Many of these compounds have high binding affinities, with the best having a bicyclo[3.3.1]nonane core and binding 3-5 times better than estradiol to both ER subtypes. Some of the compounds show significant affinity selectivity in favor of ERbeta (4- to 5-fold), and in cell-based assays for transcriptional activity most are partial agonists on ERalpha and full antagonists on ERbeta.
Salmonellosis in Orally Infected Specific Pathogen-Free C57B1 Mice (1972)

Specific pathogen-free C57B1 mice are 100 to 1,000 times as sensitive as CD-1 mice to intravenous or oral challenge by Salmonella enteritidis or S. gallinarum. Resistance to infection by S. pullorum was unaffected. Growth of Listeria monocytogenes and Mycobacterium bovis (BCG) in intravenously infected C57B1 mice was similar to that seen in CD-1 mice. Quantitative counts of viable S. enteritidis in the walls of the stomach, small intestine, cecum, and large intestine and in the corresponding intestinal contents showed that most of the oral challenge inoculum was rapidly inactivated so that, by 24 hr, less than 1% was still viable. Overnight starvation and pretreatment with bicarbonate solution increased the relative survival of the challenge approximately 10-fold. Despite the rapid and extensive inactivation of the oral inoculum within the normal intestine, significant numbers of salmonellae reached the liver and spleen by 48 hr, and this systemic infection was subsequently responsible for the death of a high proportion of the challenged animals.
Mechanisms of Cold-induced Platelet Actin Assembly (2001)

Various agonists but also chilling cause blood platelets to increase cytosolic calcium, polymerize actin, and change shape. We report that cold increases barbed end nucleation sites in octyl glucoside-permeabilized platelets by 3-fold, enabling analysis of the intermediates of this response. Although chilling does not change polyphosphoinositide (ppI) levels, a ppI-binding peptide completely inhibits cold-induced nucleation. The C terminus of N-WASp, which inhibits the Arp2/3 complex, blocks nucleation by 40%; GDPbetaS, N17Rac and N17Cdc42 have no effects. Some gelsolin translocates to the detergent-insoluble cytoskeleton after cooling. Chilled platelets from gelsolin-deficient mice have approximately 50% fewer new actin nuclei compared with platelets from wild-type mice. EGTA completely inhibits gelsolin translocation into the cytoskeleton, and the small amount of gelsolin initially there becomes soluble. Chilling releases adducin from the detergent-resistant cytoskeleton. We conclude that platelet actin filament assembly induced by cooling involves ppI-mediated actin filament barbed end uncapping and de novo nucleation independently of surface receptors or downstream signaling intermediates besides calcium. The actin-related changes occur in platelets at temperatures below 37 degrees C, suggesting that the platelet may be more activable at temperatures at the body surface than at core temperature, thereby favoring superficial hemostasis over internal thrombosis.
Contact lens wear is intrinsically inflammatory (2016)

Eye-care practitioners typically associate ocular inflammation during contact lens wear with serious complications such as microbial keratitis; however, more subtle mechanisms may be at play. This paper tests the notion that contact lens wear is intrinsically inflammatory by exploring whether uncomplicated contact lens wear meets the classical, clinical definition of inflammation - rubor (redness), calor (heat), tumor (swelling), dolor (pain) and functio laesa (loss of function) - as well as the contemporary, sub-clinical definition of inflammation (cellular and biochemical reactions). It is demonstrated that all of these clinical and sub-clinical criteria are met with hydrogel lens wear and most are met with silicone hydrogel lens wear, indicating that uncomplicated contact lens wear is intrinsically inflammatory. Consideration of both traditional and contemporary thinking about the role of inflammation in the human body leads to the perhaps surprising conclusion that the chronic, low grade, sub-clinical inflammatory status of the anterior eye during contact lens wear, which may be termed 'para-inflammation', is a positive, protective phenomenon, whereby up-regulation of the immune system, in a non-damaging way, maintains the eye in a state of 'heightened alert', ready to ward off any extrinsic noxious challenge. Characterisation of this inflammatory status may lead to the development of lens engineering or pharmacological strategies to modulate contact lens-induced inflammation, so as to render lens wear more safe and comfortable.
Paroxysmal dystonic choreoathetosis. Genetic linkage studies in a British family (1997)

Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary dystonic and choreoathetoid movements, typically several hours in duration with no sign of abnormality between attacks. Inheritance is autosomal dominant and the PDC locus has recently been assigned to the distal long arm of chromosome 2 in two families. We describe a six-generation British family with PDC and describe the results of fine genetic mapping and candidate gene linkage analysis. As part of a genome-wide search, linkage to chromosome 2q was confirmed in this family. Positive LOD scores were obtained for six markers on 2q. A LOD score of 5.08 at a recombination fraction of 0.0 was obtained for the marker D2S163. Construction of haplotypes allowed definition of a disease interval of 4 cM between the flanking markers D2S295 and D2S377. Polymorphic tandem repeats within the candidate genes CHRND (delta polypeptide of the nicotinic acetylcholine receptor) and SLC4A3 were examined yielding LOD scores of -7.68 and 6.08, respectively, at a recombination fraction of 0.0. This excludes CHRND as a candidate. Our data confirm the assignment of the locus for PDC to chromosome 2q and provide evidence for locus homogeneity in PDC. We have narrowed the disease interval to 4 cM and our findings provide support for the involvement of the gene for the chloride/bicarbonate exchanger as a candidate gene for PDC.
A Membrane-targeted BID BCL-2 Homology 3 Peptide Is Sufficient for High Potency Activation of BAX in Vitro (2006)

The multidomain pro-apoptotic proteins BAX and BAK constitute an essential gateway to mitochondrial dysfunction and programmed cell death. Among the "BCL-2 homology (BH) 3-only" members of pro-apoptotic proteins, truncated BID (tBID) has been implicated in direct BAX activation, although an explicit molecular mechanism remains elusive. We find that BID BH3 peptide alone at submicromolar concentrations cannot activate BAX or complement BID BH3 mutant-tBID in mitochondrial and liposomal release assays. Because tBID contains structurally defined membrane association domains, we investigated whether membrane targeting of BID BH3 peptide would be sufficient to restore its pro-apoptotic activity. We developed a Ni(2+)-nitrilotriacetic acid liposomal assay system that efficiently conjugates histidine-tagged peptides to a simulated outer mitochondrial membrane surface. Strikingly, nanomolar concentrations of a synthetic BID BH3 peptide that is chemically tethered to the liposomal membrane activated BAX almost as efficiently as tBID itself. These results highlight the importance of membrane targeting of the BID BH3 domain in tBID-mediated BAX activation and support a model in which tBID engages BAX to trigger its pro-apoptotic activity.
Holdfast heroics: comparing the molecular and mechanical properties ofMytilus californianusbyssal threads (2007)

The marine mussel Mytilus californianus Conrad inhabits the most wave-exposed regions of the rocky intertidal by dint of its extraordinary tenacity. Tenacity is mediated in large part by the byssus, a fibrous holdfast structure. M. californianus byssal threads, which are mechanically superior to the byssal threads of other mytilids, are composed almost entirely of a consortium of three modular proteins known as the preCols. In this study, the complete primary sequence of preCols from M. californianus was deduced and compared to that of two related species with mechanically inferior byssal threads, M. edulis Linnaeus and M. galloprovincialis Lamarck in order to explore structure-function relationships. The preCols from M. californianus are more divergent from the other two species than they are from one another. However, the degree of divergence is not uniform among the various domains of the preCols, allowing us to speculate on their mechanical role. For instance, the extra spider silk-like runs of alanine-rich sequence in the flanking domains of M. californianus may increase crystalline order, enhancing strength and stiffness. Histidine-rich domains at the termini, in contrast, are highly conserved between species, suggesting a mechanical role common to all three. Mechanical testing of pH-treated and chemically derivatized distal threads strongly suggests that histidine side chains are ligands in reversible, metal-mediated cross-links in situ. By combining the mechanical and sequence data, yield and self-healing in the distal region of threads have been modeled to emphasize the intricate interplay of enthalpic and entropic effects during tensile load and recovery.
A Closed-Form Solution to Natural Image Matting (2007)

Interactive digital matting, the process of extracting a foreground object from an image based on limited user input, is an important task in image and video editing. From a computer vision perspective, this task is extremely challenging because it is massively ill-posed -- at each pixel we must estimate the foreground and the background colors, as well as the foreground opacity ("alpha matte") from a single color measurement. Current approaches either restrict the estimation to a small part of the image, estimating foreground and background colors based on nearby pixels where they are known, or perform iterative nonlinear estimation by alternating foreground and background color estimation with alpha estimation. In this paper we present a closed-form solution to natural image matting. We derive a cost function from local smoothness assumptions on foreground and background colors, and show that in the resulting expression it is possible to analytically eliminate the foreground and background colors to obtain a quadratic cost function in alpha. This allows us to find the globally optimal alpha matte by solving a sparse linear system of equations. Furthermore, the closed-form formula allows us to predict the properties of the solution by analyzing the eigenvectors of a sparse matrix, closely related to matrices used in spectral image segmentation algorithms. We show that high quality mattes for natural images may be obtained from a small amount of user input.