gebhart/patrepeval huggingface dataset:
Activation of Growth Hormone Receptors by Growth Hormone and Growth Hormone Antagonist Dimers: Insights into Receptor Triggering (2007)

GH binds dimerized GH receptors (GHRs) to form a trimolecular complex and induces downstream signaling events. The mechanism by which GH binding converts the inactive predimerized GHR to its active signaling conformation is uncertain. GH has no axis of symmetry. Its interaction with GHR is mediated by two asymmetric binding sites on GH, each with distinct affinity. Site 1 is of high affinity and is thought to mediate the first binding step. Mutation of binding site 2 (as in the human GH mutant, G120R) disrupts the second binding but leaves site 1 binding intact. G120R is a GH antagonist; it binds only one GHR and thus fails to signal, and it prevents productive GHR binding by normal GH. We previously demonstrated that prolactin receptor signaling was achieved by a dimeric version of a prolactin antagonist. We now employ assays of cellular signaling and receptor conformational changes to examine whether GH molecules harboring two site 1 regions can trigger GHR activation. We used recombinantly produced GH-GH and G120R-G120R dimers in which monomers in tandem are connected by a short linker peptide. Rabbit GHR-expressing human fibrosarcoma cells (C14) were treated with GH, G120R, GH-GH, or G120R-G120R. As expected, GH and GH-GH, but not G120R, induced GHR disulfide linkage, as assessed by anti-GHR blotting of cell extracts resolved by SDS-PAGE under nonreducing conditions. Disulfide linkage of GHRs reflects attainment of the active signaling conformation. Likewise, GH and GH-GH, but not G120R, caused Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) activation. Notably, G120R-G120R, despite its lack of an intact site 2 in either dimer partner, also promoted GHR disulfide linkage and JAK2 and STAT5 activation, albeit less potently than either GH or GH-GH. Time-course responses of the three agonists were similar in terms of JAK2 and STAT5 activation. Pretreatment of cells with our conformation-sensitive inhibitory monoclonal antibody, anti-GHR ext-mAb, prevented ligand-induced receptor activation for all three agonists. GHR was also rendered less immunoprecipitable by anti-GHR ext-mAb after treatment with these agonists. These results are important in that they indicate that a ligand with two intact binding sites 1 causes GHR to adopt similar conformational changes as does GH and thus triggers activation of JAK2 and downstream signaling. Furthermore, we infer that there is substantial flexibility in the GHR extracellular domain, such that it productively accommodates GH dimers that are much larger than GH.
The Glomerular Injury of Preeclampsia (2007)

Preeclampsia is a pregnancy-specific disorder that complicates approximately 5% of all pregnancies, making it perhaps the most common glomerular disease in the world. It is characterized by new-onset hypertension and proteinuria, in association with a characteristic glomerular lesion, endotheliosis. "Glomerular endotheliosis" represents a specific variant of thrombotic microangiopathy that is characterized by glomerular endothelial swelling with loss of endothelial fenestrae and occlusion of the capillary lumens. Associated thrombosis is unusual. Recent evidence suggests that this unusual glomerular lesion is mediated by a soluble vascular endothelial growth factor receptor that deprives glomerular endothelial cells of the vascular endothelial growth factor that they require, leading to cellular injury and disruption of the filtration apparatus with subsequent proteinuria. This review summarizes the histologic changes and the pathogenesis of the glomerular lesions of preeclampsia.
Breakdown of the blood--aqueous barrier in the rabbit eye by infrared radiation. (1989)

Breakdown of the blood-aqueous barrier was produced by infrared radiation (IR) at a heat flux from 24 to 44 J/cm2 in pigmented, but not in albino rabbits. Blood-aqueous barrier breakdown was inhibited by indomethacin and ketamine/xylazine anesthesia mixtures, but not by [D-Trp2,D-Pro7,9]-substance P. The degree of blood-aqueous barrier breakdown could be controlled by IR flux. Two models for accurate determination of the heat flux are presented.
Druggability Analysis and Structural Classification of Bromodomain Acetyl-lysine Binding Sites (2012)

Bromodomains are readers of the epigenetic code that specifically bind acetyl-lysine containing recognition sites on proteins. Recently the BET family of bromodomains has been demonstrated to be druggable through the discovery of potent inhibitors, sparking an interest in protein-protein interaction inhibitors that directly target gene transcription. Here, we assess the druggability of diverse members of the bromodomain family using SiteMap and show that there are significant differences in predicted druggability. Furthermore, we trace these differences in druggability back to unique amino acid signatures in the bromodomain acetyl-lysine binding sites. These signatures were then used to generate a new classification of the bromodomain family, visualized as a classification tree. This represents the first analysis of this type for the bromodomain family and can prove useful in the discovery of inhibitors, particularly for anticipating screening hit rates, identifying inhibitors that can be explored for lead hopping approaches, and selecting proteins for selectivity screening.
Postweaning multisystemic wasting syndrome: Epidemiology and clinical presentation (1998)

Methods: A retrospective analysis of the production records of a 600-sow herd with clincial signs consistent with endemic PMWS was conducted.˚ Also, data elicited by a descriptive epidemiologic survey that was completed by 15 producers with herds that had confirmed PMWS was analyzed. Results: In the case herd, postweaning mortality rate peaked at 7.67% on month 9 of the epidemic, then returned within 16 months to pre-outbreak levels of 2.1%‐2.5%. The most common causes of death reported by the farm were unthriftiness (weight loss, emaciation), jaundice (liver disease), and dyspnea (respiratory disease). In the surveyed herds, PMWS was found to be a slow and progressive disease with a high case fatality rate (81.4% ±23.4%). Clinical disease was observed most commonly in pregrower barns (90%), followed by nursery (62%) and grower barns (39%). The syndrome was first noted in pigs 42 ±13.5 days of age. The most frequent clinical signs of PMWS included unthriftiness, dyspnea, pallor, rough hair coat, diarrhea, and jaundice. Postweaning mortality averaged 6.7% ± 5.1% (SD) in affected herds, and was reported as 18.3% in the most severely affected herd. Poor response to various modes of antimicrobial therapy was reported. Implications: Control of PMWS is difficult and may depend largely on pig flow, improved sanitation, and early recognition and segregation of sick pigs.
Transesterification of vegetable oils: a review (1998)

The transesterification of vegetable oils with methanol as well as the main uses of the fatty acid methyl esters are reviewed. The general aspects of this process and the applicability of different types of catalysts (acids, alkaline metal hydroxides, alkoxides and carbonates, enzymes and non-ionic bases, such as amines, amidines, guanidines and triamino(imino)phosphoranes) are described. Special attention is given to guanidines, which can be easily heterogenized on organic polymers. However, the anchored catalysts show leaching problems. New strategies to obtain non-leaching guanidine-containing catalysts are proposed. Finally, several applications of fatty acid esters, obtained by transesterification of vegetable oils, are described.
Agrin controls synaptic differentiation in hippocampal neurons. (2000)

Agrin controls the formation of the neuromuscular junction. Whether it regulates the differentiation of other types of synapses remains unclear. Therefore, we have studied the role of agrin in cultured hippocampal neurons. Synaptogenesis was severely compromised when agrin expression or function was suppressed by antisense oligonucleotides and specific antibodies. The effects of antisense oligonucleotides were found to be highly specific because they were reversed by adding recombinant agrin and could not be detected in cultures from agrin-deficient animals. Interestingly, the few synapses formed in reduced agrin conditions displayed diminished vesicular turnover, despite a normal appearance at the EM level. Thus, our results demonstrate the necessity of agrin for synaptogenesis in hippocampal neurons.
Endotoxin and lung injury. (1986)

Two things are certain: endotoxin has dramatic effects on the structure and function of the lungs in intact animals and also on isolated lung cells, and both the in vivo and in vitro effects of endotoxin are complex. In whole animals, endotoxin causes obvious and subtle effects on functions of both airways and the pulmonary circulation. These effects include diffuse lung inflammation and injury of pulmonary vascular endothelium. Endotoxin can also directly injure endothelial cells in vitro. In vivo, lung injury caused by endotoxin is at least partly dependent on the presence of granulocytes, and some evidence also suggests that both lymphocytes and macrophages may participate in the response either directly or by directing cell traffic. At least in the sheep preparation, platelets do not seem to play a major role in the lungs' response to endotoxemia. Although endotoxin can activate complement and activated complement infused into whole animals affects the lungs, it seems unlikely that complement activation alone is sufficient to explain the severe and prolonged lung injury caused by endotoxin. Cyclooxygenase metabolites of arachidonic acid appear to mediate both changes in lung mechanics and pulmonary vasoconstriction after endotoxemia. Lipoxygenase products may play a role in these responses as well as the inflammatory response and increases in vascular permeability, although evidence for these latter speculations is not firm. Lung cell injury caused by endotoxin probably is mediated at least in part by generation of free radicals. Inflammatory cells, especially neutrophils, are one source of these toxic oxygen species, but intracellular generation of free radicals within lung cells per se may also be stimulated by endotoxin and account for some of the lung injury. Likewise, inflammatory-cell-derived proteinases may mediate endotoxin-induced injury of lung cells and, as with chronic lung diseases, balance between proteinases and antiproteinases could be important. The fact that free radicals can inactivate antiproteinases, and antiproteinases can act as free radical scavengers, may suggest a complex relationship among the several possible mediators of toxicity. Cyclic nucleotide metabolism is affected in whole animals and isolated lung cells by endotoxin and these classic second messengers could be involved in the pathogenetic sequence, but exactly how is unclear. Chronic effects of endotoxin on the lungs may provide a pathogenetic link between acute lung injury and chronic changes in lung structure and function.(ABSTRACT TRUNCATED AT 400 WORDS)
Synthetic carbohydrate-based vaccines: synthesis of an L-glycero-D-manno-heptose antigen–T-epitope–lipopeptide conjugate (1997)

A facile and highly efficient synthesis of a glycopeptidolipid containing a heptose sugar, a synthetic T-epitope and a synthetic immunoadjuvant is presented which represents an important step towards the development of a fully synthetic vaccine against Neisseria meningitidis.
Characterization of thed-Xylulose 5-Phosphate/d-Fructose 6-Phosphate Phosphoketolase Gene (xfp) fromBifidobacterium lactis (2001)

A D-xylulose 5-phosphate/D-fructose 6-phosphate phosphoketolase (Xfp) from the probiotic Bifidobacterium lactis was purified to homogeneity. The specific activity of the purified enzyme with D-fructose 6-phosphate as a substrate is 4.28 Units per mg of enzyme. K(m) values for D-xylulose 5-phosphate and D-fructose 6-phosphate are 45 and 10 mM, respectively. The native enzyme has a molecular mass of 550,000 Da. The subunit size upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (90,000 Da) corresponds with the size (92,529 Da) calculated from the amino acid sequence of the isolated gene (named xfp) encoding 825 amino acids. The xfp gene was identified on the chromosome of B. lactis with the help of degenerated nucleotide probes deduced from the common N-terminal amino acid sequence of both the native and denatured enzyme. Comparison of the deduced amino acid sequence of the cloned gene with sequences in public databases revealed high homologies with hypothetical proteins (26 to 55% identity) in 20 microbial genomes. The amino acid sequence derived from the xfp gene contains typical thiamine diphosphate (ThDP) binding sites reported for other ThDP-dependent enzymes. Two truncated putative genes, pta and guaA, were localized adjacent to xfp on the B. lactis chromosome coding for a phosphotransacetylase and a guanosine monophosphate synthetase homologous to products of genes in Mycobacterium tuberculosis. However, xfp is transcribed in B. lactis as a monocistronic operon. It is the first reported and sequenced gene of a phosphoketolase.
Ambipolar Schottky-barrier TFTs (2002)

A novel Schottky-barrier metal-oxide-semiconductor thin-film transistor (SBTFT) was successfully demonstrated and characterized. The new SBTFT device features a field-induced-drain (FID) region, which is controlled by a metal field-plate lying on top of the passivation oxide. The FID region is sandwiched between the silicided drain and the active channel region. Carrier types and the conductivity of the transistor are controlled by the metal field-plate. The device is thus capable of ambipolar operation. Excellent ambipolar performance with on/off current ratios over 10/sup 6/ for both p- and n-channel operations was realized simultaneously on the same device fabricated with polysilicon active layer. Moreover, the off-state leakage current shows very weak dependence on the gate-to-drain voltage difference with the FID structure. Finally, the effects of FID length are explored.
An analysis of pilot symbol assisted QPSK for digital mobile communications (2002)

Embedded pilot symbols, which provide an amplitude and phase reference to mitigate the effects of rapid fading in mobile communications, are discussed. It is shown that, unlike the pilot tone systems, pilot symbol assisted modulation (PSAM) does not affect the transmitted pulse shape or the peak-to-average power ratio, and implementation is straightforward. Closed-form expressions are presented for the optimized receiver coefficients, and for the bit-error rate (BER) in binary phase-shift keying (BPSK) and quadrature phase-shift keying (QPSK) or pi /4-offset QPSK. It is also shown that the error rates obtained are lower than those for differential detection for any combination of signal-to-noise ratio (SNR) and Doppler spread, and the performance is within 1 dB of a perfect reference system under slow fading conditions and within 3 dB when the Doppler spread is 5% of the symbol rate.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function (2010)

L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models.
Review of Artificial Muscle Based on Contractile Polymers (1991)

An artificial muscle with strength and speed equal to that of a human muscle may soon be possible. Polymer gels exhibit abrupt volume changes in response to variations in their external conditions - shrinking or swelling up to 1000 times their original volume. Through the conversion of chemical or electrical energy into mechanical work, a number of devices have already been constructed which produce forces up to 100N/cm2 and contraction rates on the order of a second. Though the promise of an artificial muscle is real, many fundamental physical and engineering questions remain before the extent or limit of these devices is known.
Adenosine Modification May Be Preferred for Reducing siRNA Immune Stimulation (2012)

The immune stimulation induced by short interfering RNAs (siRNAs) has been reported to be quieted or abrogated by methoxy or fluoro modifications of the 2' position of the ribose sugar. However, variables such as the type of modification, nucleotide preference, and strand bias have not been systematically evaluated. Here, we report the results of a screen of several modified siRNAs via a human peripheral blood monocyte cytokine induction assay. Unlike corresponding modifications of guanosine, cytidine, or uridine, 2'-fluoro modification of adenosine significantly reduced cytokine induction while retaining siRNA knockdown activity. The results of this study suggest adenosine as an optimal target for modification.
Carbon dioxide pressure-concentration relationship in arterial and mixed venous blood during exercise (2001)

To calculate cardiac output by the indirect Fick principle, CO(2) concentrations (CCO(2)) of mixed venous (Cv(CO(2))) and arterial blood are commonly estimated from PCO(2), based on the assumption that the CO(2) pressure-concentration relationship (PCO(2)-CCO(2)) is influenced more by changes in Hb concentration and blood oxyhemoglobin saturation than by changes in pH. The purpose of the study was to measure and assess the relative importance of these variables, both in arterial and mixed venous blood, during rest and increasing levels of exercise to maximum (Max) in five healthy men. Although the mean mixed venous PCO(2) rose from 47 Torr at rest to 59 Torr at the lactic acidosis threshold (LAT) and further to 78 Torr at Max, the Cv(CO(2)) rose from 22.8 mM at rest to 25.5 mM at LAT but then fell to 23.9 mM at Max. Meanwhile, the mixed venous pH fell from 7.36 at rest to 7.30 at LAT and to 7.13 at Max. Thus, as work rate increases above the LAT, changes in pH, reflecting changes in buffer base, account for the major changes in the PCO(2)-CCO(2) relationship, causing Cv(CO(2)) to decrease, despite increasing mixed venous PCO(2). Furthermore, whereas the increase in the arteriovenous CCO(2) difference of 2.2 mM below LAT is mainly due to the increase in Cv(CO(2)), the further increase in the arteriovenous CCO(2) difference of 4.6 mM above LAT is due to a striking fall in arterial CCO(2) from 21.4 to 15.2 mM. We conclude that changes in buffer base and pH dominate the PCO(2)-CCO(2) relationship during exercise, with changes in Hb and blood oxyhemoglobin saturation exerting much less influence.
Human Resource Management: A Practical Approach (1996)

Part 1 The context of human resources: an introduction to human resources management employment discrimination laws human resource planning. Part 2 Staffing: recruitment the selection process career management. Part 3 Evaluating and compensating: performance management compensation administration pay-for-performance benefits. Part 4 Improving the workplace: employee training and development work redesign for productivity improvement safety and health in the workplace. Part 5 Maintaining effective employee-employer relationships - unions: the organizing process unions, negotiating and administering and agreement employee rights.
Bootstrap confidence levels for phylogenetic trees (1996)

Evolutionary trees are often estimated from DNA or RNA sequence data. How much confidence should we have in the estimated trees? In 1985, Felsenstein [Felsenstein, J. (1985) Evolution 39, 783–791] suggested the use of the bootstrap to answer this question. Felsenstein’s method, which in concept is a straightforward application of the bootstrap, is widely used, but has been criticized as biased in the genetics literature. This paper concerns the use of the bootstrap in the tree problem. We show that Felsenstein’s method is not biased, but that it can be corrected to better agree with standard ideas of confidence levels and hypothesis testing. These corrections can be made by using the more elaborate bootstrap method presented here, at the expense of considerably more computation.
Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence—first results of an inter‐ethnic breast cancer study (2004)

Overexpression of the epidermal growth factor receptor (EGFR) is a common finding in invasive breast cancer and represents a potential target for new treatment options. However, little is known about the parameters that might indicate a potential clinical response for these anti-EGFR-based therapies. In order to gain further insights into the interplay between the length of a CA-SSR I repeat in intron 1 of egfr, copy numbers of this untranslated regulatory sequence, and protein expression, the present study investigated breast cancers from Germans and Japanese patients by microsatellite analysis, quantitative 5' nuclease assay by egfr enzyme-linked immunosorbent assay (ELISA), and comparative genomic hybridization (CGH). Japanese breast cancer patients displayed significantly longer alleles for the CA-SSR I repeat (p < 0.001), associated with significantly lower EGFR expression (mean 65 versus 36 fmol/mg membrane protein). Allelic imbalance (restricted to CA-SSR I) was observed in 55% of the informative Japanese breast cancers compared with only 34% of the German breast cancer reference group. Using a quantitative 5' nuclease assay for egfr, a significantly higher percentage of Japanese breast cancer patients revealed amplifications of the CA-SSR I repeat (p < 0.01). Japanese patients with these amplifications were characterized by a significantly higher EGFR content compared with the German breast cancer patients (p < 0.05). These data show, on the one hand, that the correlation of EGFR overexpression and an inherited CA repeat polymorphism within intron 1 of egfr is a general finding in breast cancer, as has been shown previously. On the other hand, the data demonstrate clearly for the first time an interaction between the length of a polymorphism in intron 1 of egfr as an inherited genetic factor and the frequency of egfr amplification, as an acquired genetic factor, both factors contributing to EGFR overexpression in breast cancer. This new knowledge about mechanisms of regulation of EGFR expression might serve as an additional basis for evaluating anti-EGFR-based therapies.