gebhart/patrepeval huggingface dataset:
Interactions Between the Melanocortin System and Leptin in Control of Sympathetic Nerve Traffic (1999)

Leptin plays an important role in regulation of body weight through regulation of food intake and sympathetically mediated thermogenesis. The hypothalamic melanocortin system, via activation of the melanocortin-4 receptor (MC4-R), decreases appetite and weight, but its effects on sympathetic nerve activity (SNA) are unknown. In addition, it is not known whether sympathoactivation to leptin is mediated by the melanocortin system. We tested the interactions between these systems in regulation of brown adipose tissue (BAT) and renal and lumbar SNA in anesthetized Sprague-Dawley rats. Intracerebroventricular administration of the MC4-R agonist MT-II (200 to 600 pmol) produced a dose-dependent sympathoexcitation affecting BAT and renal and lumbar beds. This response was completely blocked by the MC4-R antagonist SHU9119 (30 pmol ICV). Administration of leptin (1000 microg/kg IV) slowly increased BAT SNA (baseline, 41+/-6 spikes/s; 6 hours, 196+/-28 spikes/s; P=0.001) and renal SNA (baseline, 116+/-16 spikes/s; 6 hours, 169+/-26 spikes/s; P=0.014). Intracerebroventricular administration of SHU9119 did not inhibit leptin-induced BAT sympathoexcitation (baseline, 35+/-7 spikes/s; 6 hours, 158+/-34 spikes/s; P=0.71 versus leptin alone). However, renal sympathoexcitation to leptin was completely blocked by SHU9119 (baseline, 142+/-17 spikes/s; 6 hours, 146+/-25 spikes/s; P=0.007 versus leptin alone). This study demonstrates that the hypothalamic melanocortin system can act to increase sympathetic nerve traffic to thermogenic BAT and other tissues. Our data also suggest that leptin increases renal SNA through activation of hypothalamic melanocortin receptors. In contrast, sympathoactivation to thermogenic BAT by leptin appears to be independent of the melanocortin system.
Expression of the potent vasoconstrictor endothelin in the human central nervous system. (1990)

Endothelin is a potent vasoconstrictive peptide initially charac- terized as a product of endothelial cells. To examine the po- tential role of endothelin as a neuropeptide, we studied its distribution in the human central nervous system. RNA blot hybridization provided evidence of endothelin gene transcription in a variety of functional regions of the brain. In situ hybridization confirmed the widespread pattern of endothelin transcription and indicated that the highest density of cells containing endothelin mRNA is in the hypothalamus. This technique localized endothelin transcription to cells of the ner- vous system as well as the vascular endothelium. Immunocytochemical studies detected endothelin immunoreactivity in neurons, providing evidence of the synthesis of the peptide in this cell type and confirming that endothelin is a neuropeptide. Although the prominent expression of endothelin in the hypothalamus may indicate a central vasoregulatory role for the peptide, the widespread distribution of endothelin in neurons in other areas of the brain implies a more fundamental role in the regulation of nervous system function. (
Actinobacillus succinogenes sp. nov., a novel succinic-acid-producing strain from the bovine rumen (1999)

Strain 130ZT was isolated from the bovine rumen. It is a facultatively anaerobic, pleomorphic, Gram-negative rod. It exhibits a 'Morse code' form of morphology, which is characteristic of the genus Actinobacillus. Strain 130ZT is a capnophilic, osmotolerant succinogen that utilizes a broad range of sugars. It accumulates high concentrations of succinic acid (> 70 g l-1). Strain 130ZT is positive for catalase, oxidase, alkaline phosphatase and beta-galactosidase, but does not produce indole or urease. Acid but no gas is produced from D-glucose and D-fructose. 16S rRNA sequence analysis places strain 130ZT within the family Pasteurellaceae; the most closely related members of the family Pasteurellaceae have 16S rRNA similarities of 95.5% or less with strain 130ZT. Strain 130ZT was compared with Actinobacillus lignieresii and the related Bisgaard Taxa 6 and 10. Based upon morphological and biochemical properties, strain 130ZT is most similar to members of the genus Actinobacillus within the family Pasteurellaceae. It is proposed that strain 130ZT be classified as a new species, Actinobacillus succinogenes. The type strain of Actinobacillus succinogenes sp. nov. is ATCC 55618T.
Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease (1997)

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22–23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.
Photocleavable peptide–oligonucleotide conjugates for protein kinase assays by MALDI-TOF MS (2012)

Robust methods for highly parallel, quantitative analysis of cellular protein tyrosine kinase activities may provide tools critically needed to decipher oncogenic signaling, discover new targeted drugs, diagnose cancer and monitor patients. Here, we describe proof-of-principle for a novel protein kinase assay with the potential to help overcome these challenges. MALDI-TOF mass spectrometry provides an ideal tool for label-free multiplexed analysis of peptide phosphorylation, but is poorly matched to homogeneous assays and complex samples. Thus, we conjugated a common oligonucleotide tag to multiple peptide substrates, offering efficient capture from solution-phase kinase reactions by annealing to the complementary sequence tethered to PEG-passivated superparamagnetic microparticles. To enable reversible conjugation, we developed a novel bifunctional cross-linker allowing simple and efficient preparation of photocleavable peptide-oligonucleotide conjugates. After washing away contaminants and following photorelease, MALDI-TOF analysis yielded relative phosphorylation of each peptide with high sensitivity and specificity. Validating the hybridization-mediated multiplexed kinase assay, when three peptide substrate-oligonucleotide conjugates were mixed with the tyrosine kinase c-Abl and ATP, we readily observed their differential phosphorylation yet measured a common IC(50) for the Abl kinase inhibitor imatinib. This new assay enables analysis of protein kinase activities in a multiplexed format amenable to screening inhibitors against multiple kinases in parallel, an important capability for drug discovery and predictive diagnostics.
Ribonuclease A: Revealing Structure-Function Relationships with Semisynthesis (1995)

Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P–O(5′) bonds in RNA. Structural analyses had suggested that the active-site lysine residue (K41) may interact preferentially with the transition state for covalent bond cleavage, thus facilitating catalysis. Here, site-directed mutagenesis and semisynthesis were combined to probe the role of K41 in the catalysis of RNA cleavage. Recombinant DNA techniques were used to replace K41 with an arginine residue (K41R) and with a cysteine residue (K41C), which had the only sulfhydryl group in the native protein. The value of k(cat)/K(m) for cleavage of poly(C) by K41C RNase was 10(5)-fold lower than that by the wild-type enzyme. The sulfhydryl group of K41C RNase A was alkylated with 5 different haloalkylamines. The value of k(cat)/K(m) for the resulting semisynthetic enzymes and K41R RNase A were correlated inversely with the values of pK(a) for the side chain of residue 41. Further, no significant catalytic advantage was gained by side chains that could donate a second hydrogen bond. These results indicate that residue 41 donates a single hydrogen bond to the rate-limiting transition state during catalysis.
Alkane Cascade Polymers Possessing Micellar Topology: Micellanoic Acid Derivatives (1991)

The addition of a tertiary radical to an electron-deficient alkene proves to be the decisve step in the synthesis of the four-directional cascade polymers 1 and 2, which have no heteroatoms in the initial core, in the branching centers, or in the repeat units. Only the periphery is highly fuctionalized.
High aspect ratio TSV copper filling with different seed layers (2008)

The paper addresses the through silicon via (TSV) filling using electrochemical deposition (ECD) of copper. The impact of seed layer nature on filling ratio and void formation will be discussed with respect to via diameter and via depth. Based on the spherolyte Cu200 the electrolyte for the copper electrochemical deposition was modified for good filling behavior. Thermomechanical modeling and simulation was performed for reliability assessment.
Navier-Stokes turbine heat transfer predictions using two-equation turbulence (1992)

Navier-Stokes calculations were carried out in order to predict the heat transfer rates on turbine blades. The calculations were performed using TRAF2D which is a two-dimensional, explicit, finite volume mass-averaged Navier-Stokes solver. Turbulence was modeled using q-omega and k-epsilon two-equation models and the Baldwin-Lomax algebraic model. The model equations along with the flow equations were solved explicitly on a non-periodic C grid. Implicit residual smoothing (IRS) or a combination of multigrid technique and IRS was applied to enhance convergence rates. Calculations were performed to predict the Stanton number distributions on the first stage vane and blade row as well as the second stage vane row of the Rocketdyne Space Shuttle Main Engine (SSME) high pressure fuel turbine. The comparison with the experimental results, although generally favorable, serves to highlight the weaknesses of the turbulence models and the possible areas of improving these models for use in turbomachinery heat transfer calculations.
Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus (1998)

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7-14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4(+) T cell counts.
Multiple members of the E2F transcription factor family are the products of oncogenes. (1995)

The retinoblastoma gene product (pRB) is a known tumor suppressor, capable of arresting growth in mid-to-late G1. Part of its growth suppression action arises from interaction(s) with one or more members of the E2F family of transcription factors. These proteins most likely contribute to progression from G0 to S phase in mammalian cells, and pRB binding most likely inhibits aspects of their suspected growth-promoting function. Given their growth-stimulating potential, we asked whether one or more E2F alleles can function as oncogenes. Uncloned pools of NIH 3T3 cells producing the pRB binding target E2F-1, E2F-2, or E2F-3 grew in semisolid medium. In addition, they grew to much higher saturation density than controls. From the study of cells producing selected E2F-1 mutant species, it appears that E2F DNA-binding function contributes to, and pRB/E2F binding suppresses, soft-agar growth. Thus, three E2F family members can act as oncogene products, suggesting that part of the normal role of pRB is to down-modulate this potential activity.
Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles (2006)

There has been considerable progress recently towards developing therapeutic strategies for Huntington's disease (HD), with several compounds showing beneficial effects in transgenic mouse models. However, human trials in HD are difficult, costly and time-consuming due to the slow disease course, insidious onset and patient-to-patient variability. Identification of molecular biomarkers associated with disease progression will aid the development of effective therapies by allowing further validation of animal models and by providing hopefully more sensitive measures of disease progression. Here, we apply metabolic profiling by gas chromatography-time-of-flight-mass spectrometry to serum samples from human HD patients and a transgenic mouse model in a hypothesis-generating search for disease biomarkers. We observed clear differences in metabolic profiles between transgenic mice and wild-type littermates, with a trend for similar differences in human patients and control subjects. Thus, the metabolites responsible for distinguishing transgenic mice also comprised a metabolic signature tentatively associated with the human disease. The candidate biomarkers composing this HD-associated metabolic signature in mouse and humans are indicative of a change to a pro-catabolic phenotype in early HD preceding symptom onset, with changes in various markers of fatty acid breakdown (including glycerol and malonate) and also in certain aliphatic amino acids. Our data raise the prospect of a robust molecular definition of progression of HD prior to symptom onset, and if validated in a genuinely prospective fashion these biomarker trajectories could facilitate the development of useful therapies for this disease.
The fundamental limit on binary switching energy for terascale integration (TSI) (2000)

The fundamental limit on signal energy transfer during a binary switching transition is E/sub s/(min)=(ln2)kT. Derivation of precisely this result based on two entirely distinct physical models confirms its validity. The first model is an ideal MOSFET operating in a CMOS inverter circuit at the limit of its capacity for binary signal discrimination. The second is an isolated interconnect treated as a noisy communication channel. Both models are relevant to modern terascale integration.
Modulation of L-selectin ligand expression during an immune response accompanying tumorigenesis in transgenic mice. (1996)

Immune surveillance depends on lymphocyte access to tissue. Lymphocytes emigrate from blood when adhesion receptors such as L-selectin and the alpha 4 beta 7 integrin on these cells bind to ligands expressed on venular endothelium. Among transgenic mouse lines expressing an oncoprotein (Tag) in islet beta cells, some recognize Tag as nonself. In these mice, Tag expression elicits both beta cell hyperplasia with subsequent progression to tumors and lymphocytic infiltration. Endothelial ligands for L-selectin and alpha 4 beta 7 were upregulated in infiltrated islets in these transgenic mice. These ligands were not expressed in tumors, which were devoid of lymphocytic infiltration. In contrast, the adhesion molecules PECAM-1, ICAM-1, and VCAM-1 were expressed on endothelium in both noninfiltrated tumors and infiltrated islets. Thus, upregulation of expression of endothelial ligands for L-selectin and alpha 4 beta 7 may contribute to autoimmune infiltration. Repression of expression of these same ligands may be involved in the failure of tumor immunity.
Mechanical Esophageal Deflection During Ablation of Atrial Fibrillation (2006)

To prevent esophageal damage during ablation of atrial fibrillation, we developed a technique to move the esophagus away from a desired ablation site too close to the esophagus. Under fluoroscopy, a transesophageal echocardiography probe was used to deflect the barium-opacified esophagus from the ablation site. This technique was successfully employed in three patients where critical sites of the posterior left atrial wall were very close to the esophagus.
Estimation of spore hydrophobicity for members of the genera Beauveria, Metarhizium, and Tolypocladium by salt-mediated aggregation and sedimentation (1997)

The surface hydrophobicities of fungal spores from the entomopathogenic genera Beauveria, Metarhizium, and Tolypocladium were quantitatively measured and compared using a novel assay employing salt-mediated aggregation and sedimentation (SAS). Spores with greater hydrophobicities were easily identified by their aggregation and sedimentation out of suspension at faster rates under lower salt concentrations. Of the three ammonium salts investigated for their salting-out potentials, ammonium sulfate gave the most pronounced effect, closely followed by ammonium chloride, and then ammonium acetate. Using the SAS assay, spores exhibited more pronounced hydrophobic properties at pH 5.8 than at higher pH values of 6.8 and 7.8. The effects of temperature and spore concentration upon the SAS assay were also investigated, with greater spore sedimentation occurring at elevated temperature. By plotting SAS values for two ammonium salt concentrations (0.01 and 0.1 M) in a coordinate system, it was possible to differentiate the hydrophobicities of all five spore isolates, clearly demonstrating the superiority of SAS over an existing phase-exclusion assay. The significance and potential of the SAS assay are also discussed.Key words: fungal spores, hydrophobicity, microassay, SAS, salting out, microbial insecticides.
Immunomodulation Targeting Abnormal Protein Conformation Reduces Pathology in a Mouse Model of Alzheimer's Disease (2010)

Many neurodegenerative diseases are characterized by the conformational change of normal self-proteins into amyloidogenic, pathological conformers, which share structural properties such as high b-sheet content and resistance to degradation. The most common is Alzheimer's disease (AD) where the normal soluble amyloid b (sAb) peptide is converted into highly toxic oligomeric Ab and fibrillar Ab that deposits as neuritic plaques and congophilic angiopathy. Currently, there is no highly effective treatment for AD, but immunotherapy is emerging as a potential disease modifying intervention. A major problem with most active and passive immunization approaches for AD is that both the normal sAb and pathogenic forms are equally targeted with the potential of autoimmune inflammation. In order to avoid this pitfall, we have developed a novel immunomodulatory method that specifically targets the pathological conformations, by immunizing with polymerized British amyloidosis (pABri) related peptide which has no sequence homology to Ab or other human proteins. We show that the pABri peptide through conformational mimicry induces a humoral immune response not only to the toxic Ab in APP/PS1 AD transgenic mice but also to paired helical filaments as shown on AD human tissue samples. Treated APP/PS1 mice had a cognitive benefit compared to controls (p,0.0001), associated with a reduction in the amyloid burden (p = 0.0001) and Ab40/42 levels, as well as reduced Ab oligomer levels. This type of immunomodulation has the potential to be a universal b-sheet disrupter, which could be useful for the prevention or treatment of a wide range of neurodegenerative diseases.
Photoluminescence and electroluminescence of a new blue-emitting homoleptic iridium complex (2006)

A new electrophosphorescent material, iridium(III)tris(5-(2,4-difluoro-phenyl)-10,10- dimethyl-4-aza-tricycloundeca-2,4,6-triene), Ir(F2-mppy)3, has been synthesized and characterized. Ir(F2-mppy)3 shows strong blue emission peaking at 475nm with a high phosphorescent quantum yield (ΦPL) of 0.72 in degassed toluene. Electroluminescent devices with a structure of indium tin oxide (ITO)/NPB (40nm)∕Ir(F2-mppy)3(x):CBP (30nm)/BCP (6nm)∕Alq3 (20nm)∕Mg:Ag (10:1) and 15% (10%) exhibit a maximum luminous power efficiency of 9.58lm∕W (7.68lm∕W), CIE coordinates (x=0.18,y=0.36) (x=0.17,y=0.29), and a maximum luminance of ∼9000cd∕m2 at 12.5V (∼6000cd∕m2 at 11.5V).
Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy (2016)

Uniformly adopted response criteria are essential for assessment of therapies incorporating conventional chemotherapy and chemoimmunotherapy regimens. Recently, immunomodulatory agents, such as immune checkpoint inhibitors, have demonstrated impressive activity in a broad range of lymphoma histologies. However, these agents may be associated with clinical and imaging findings during treatment suggestive of progressive disease (PD) despite evidence of clinical benefit (eg, tumor flare or pseudo-progression). Considering this finding as PD could lead to patients being prematurely removed from a treatment from which they actually stand to benefit. This phenomenon has been well described with checkpoint blockade therapy in solid tumors and anecdotally seen in lymphoma as well. To address this issue in the context of lymphoma immunomodulatory therapy, a workshop was convened to provide provisional recommendations to modify current response criteria in patients receiving these and future agents in clinical trials. The term "indeterminate response" was introduced to identify such lesions until confirmed as flare/pseudo-progression or true PD by either biopsy or subsequent imaging.
Molecular Targeting of Platelet-Derived Growth Factor B by Imatinib Mesylate in a Patient With Metastatic Dermatofibrosarcoma Protuberans (2002)

Imatinib mesylate is highly active in dermatofibrosarcoma protuberans. The dramatic response seen in this patient demonstrates that inhibition of PDGFB receptor tyrosine kinase activity can significantly impact viability of at least one type of solid tumor.
A self-terminating low-voltage swing CMOS output driver (1988)

A CMOS output pad driver circuit is described that automatically series-terminates a driven line in the line's characteristic impedance. The circuit has advantages in speed, power, and size over conventional designs. The key idea is the use of emitter-coupled logic (ECL) compatible low-voltage swings for signaling, combined with the use of the driver transistor as both a switch and as a termination resistor. An on-chip measurement circuit dynamically adjusts the impedance of the driver to match the impedance of an external reference impedance standard, allowing the circuit to compensate for both chip and board level fabrication variations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>