gebhart/patrepeval huggingface dataset:
Proton transfer in methylmalonyl-CoA epimerase from Propionibacterium shermanii. Studies with specifically tritiated (2R)-methylmalonyl-CoA as substrate (1983)

(2R)-Methyl[2-3H]malonyl-CoA was used as the substrate for methylmalonyl-CoA epimerase from Propionibacterium shermanii, under conditions where the (2S)-methylmalonyl-CoA product was removed enzymically as fast as it was formed, and the fate of the label was monitored at different extents of reaction. Very little, if any, tritium is found attached to the C-2 position in the (2S)-epimer product (isolated as propionyl-CoA). Evidently, the hydrogen atom of the new C-H bond in the product is essentially solvent-derived. The rate of tritium release into the solvent is lower than the rate of product formation, and shows a primary kinetic tritium-isotope effect on kcat./Km of 2.3 +/- 0.1. The specific radioactivity of the remaining substrate rises slowly during the epimerase-catalysed reaction, and this provides an independent estimate of the primary kinetic tritium-isotope effect on kcat./Km of 1.6 +/- 0.5. These results, taken together, indicate that the mechanistic pathway of the epimerase-catalysed reaction resembles that established for proline racemase [Cardinale & Abeles, (1968) Biochemistry 7, 3970-3978], in which two enzyme bases are involved in catalysis. One base removes the proton from the substrate, the second provides the new proton, and there is no fast isotopic exchange between enzyme-bound intermediates and solvent protons.
Three-Dimensional Plasmon Rulers (2011)

Plasmon rulers can be used to determine nanoscale distances within chemical or biological species. They are based on the spectral shift of the scattering spectrum when two plasmonic nanoparticles approach one another. However, the one-dimensionality of current plasmon rulers hampers the comprehensive understanding of many intriguing processes in soft matter, which take place in three dimensions. We demonstrated a three-dimensional plasmon ruler that is based on coupled plasmonic oligomers in combination with high-resolution plasmon spectroscopy. This enables retrieval of the complete spatial configuration of complex macromolecular and biological processes as well as their dynamic evolution.
Dependence of RF Heating on SAR and Implant Position in a 1.5T MR System (2007)

The rise in temperature in deep tissue was estimated to be higher than 1.0 degrees C for SAR above 0.4 W/kg. RF heating was greatest when the implant was set parallel to B(0). In MR imaging of patients with implants, there is a risk of RF heating when the loop of the eddy current is formed inside the body.
Pulmonary Thermal Ablation: Comparison of Radiofrequency and Microwave Devices by Using Gross Pathologic and CT Findings in a Swine Model (2009)

Microwave ablation with a 17-gauge high-power triaxial antenna creates larger and more circular zones of ablation than does a similarly sized RF applicator in a preclinical animal model. Microwave ablation may be a more effective treatment of lung tumors.
Apolipoprotein B synthesis by human liver and intestine in vitro. (1986)

The synthesis of apolipoprotein B (apoB) was examined in human fetal and adult intestine and liver. Intestine and liver were minced and then incubated with [3H]leucine, homogenized, and subjected to immunoprecipitation with antiserum that recognized both apoB-100 and apoB-48 (forms of apoB found in low density lipoproteins and in chylomicrons, respectively). Immunoprecipitates of fetal and adult liver contained radioactivity in a single apoB-100 peak when examined by NaDodSO4/polyacrylamide gel electrophoresis. Intestine from fetuses at 11 weeks of gestation incorporated radioactivity mainly into apoB-100, with little incorporation into apoB-48. Sixteen-week fetal intestine showed both apoB-100 and apoB-48, whereas adult intestine incorporated radioactivity only into apoB-48. Pulse-chase experiments with 11- and 16-week fetal intestine showed no evidence for the conversion of apoB-100 to apoB-48. Incubation of intestinal homogenates with fetal liver apoB-100 did not result in the conversion of apoB-100 to smaller forms of apoB. A cDNA probe to hepatic apoB-100 identified a single, 18-kilobase transcript in poly(A)+ RNA from fetal and adult liver and fetal intestine of all ages. These studies define the developmental pattern of apoB synthesis in human fetal and adult liver and intestine. No evidence could be found for the conversion of apoB-100 to apoB-48. The finding of a single mRNA transcript despite the form of apoB synthesized in each tissue is discussed.
Cell Cycle—Regulated Binding of c-Abl Tyrosine Kinase to DNA (1992)

The proto-oncogene c-abl encodes a protein tyrosine kinase that is localized in the cytoplasm and the nucleus. The large carboxyl-terminal segment of c-Abl was found to contain a DNA-binding domain that was necessary for the association of c-Abl with chromatin. The DNA-binding activity of c-Abl was lost during mitosis when the carboxyl-terminal segment became phosphorylated. In vitro phosphorylation of the DNA-binding domain by cdc2 kinase abolished DNA binding. Homozygous mutant mice expressing a c-Abl tyrosine kinase without the DNA-binding domain have been reported to die of multiple defects at birth. Thus, binding of the c-Abl tyrosine kinase to DNA may be essential to its biological function.
PORCINE CARTILAGE TRANSPLANTS IN THE CYNOMOLGUS MONKEY (1998)

Treatment of cartilage xenografts with alpha-galactosidase successfully removes alpha-gal epitopes from porcine cartilage. Transplantation of the treated cartilage results in the production of only anti-porcine cartilage-specific antibodies and a reduced inflammatory response consisting primarily of macrophages infiltrating into the cartilage.
Highlights I. Genetically Modified Organisms II. Environmental Change, Health and Socioeconomic Development III. Ecosystems Approach to Municipal Management (1993)

I. The release of GMOs into the environment would improve food supplies and benefit pollution control but in view of the potential risks the public should be fully aquainted with all aspects of the problem. II. Describes a report produced by the WHO, which analyses the ways in which human needs and activities affect the environment. III. Summarizes an article describing a concept for an international network of municipalities which are dedicated to an ecosystems approach to municipal management.
Cholesterol Perturbation in Mice Results in p53 Degradation and Axonal Pathology through p38 MAPK and Mdm2 Activation (2010)

Perturbation of lipid metabolism, especially of cholesterol homeostasis, can be catastrophic to mammalian brain, as it has the highest level of cholesterol in the body. This notion is best illustrated by the severe progressive neurodegeneration in Niemann-Pick Type C (NPC) disease, one of the lysosomal storage diseases, caused by mutations in the NPC1 or NPC2 gene. In this study, we found that growth cone collapse induced by genetic or pharmacological disruption of cholesterol egress from late endosomes/lysosomes was directly related to a decrease in axonal and growth cone levels of the phosphorylated form of the tumor suppressor factor p53. Cholesterol perturbation-induced growth cone collapse and decrease in phosphorylated p53 were reduced by inhibition of p38 mitogen-activated protein kinase (MAPK) and murine double minute (Mdm2) E3 ligase. Growth cone collapse induced by genetic (npc1-/-) or pharmacological modification of cholesterol metabolism was Rho kinase (ROCK)-dependent and associated with increased RhoA protein synthesis; both processes were significantly reduced by P38 MAPK or Mdm2 inhibition. Finally, in vivo ROCK inhibition significantly increased phosphorylated p53 levels and neurofilaments in axons, and axonal bundle size in npc1-/- mice. These results indicate that NPC-related and cholesterol perturbation-induced axonal pathology is associated with an abnormal signaling pathway consisting in p38 MAPK activation leading to Mdm2-mediated p53 degradation, followed by ROCK activation. These results also suggest new targets for pharmacological treatment of NPC disease and other diseases associated with disruption of cholesterol metabolism.
Assessment of flow-mediated dilation in humans: a methodological and physiological guideline (2010)

Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.
Evidence-based pharmacotherapy of Generalized Anxiety Disorder (2005)

Generalized Anxiety Disorder (GAD) is a common and often disabling disorder. This paper reviews the pharmacological treatment of GAD, based on the findings of published meta-analyses and randomized placebo-controlled studies. In doing so, it aims to address three fundamental questions: What is the first-line treatment for GAD? How long should treatment continue? What is the best intervention in patients who do not respond to first-line and second-line treatments? Due to their efficacy in GAD and comorbid anxiety and depressive disorders, their tolerability and safety, certain selective serotonin re-uptake inhibitors (escitalopram, paroxetine, sertraline) should be considered the first-line treatment for most patients, although the serotonin-noradrenaline re-uptake inhibitor venlafaxine is a reasonable alternative. Little is known about the optimal length of therapy after response to acute treatment but relapse-prevention studies with paroxetine suggest that continuation treatment should last for at least 6 months. The management of patients who do not respond to first-line treatment is uncertain, but some patients may benefit from certain tricyclic antidepressants, buspirone, or pregabalin.
Synthesis and Evaluation of Novel Chalcone Derivatives with 99mTc/Re Complexes as Potential Probes for Detection of β-Amyloid Plaques (2010)

Four (99m)Tc-labeled chalcone derivatives and their corresponding rhenium analogues were tested as potential probes for imaging β-amyloid plaques. The chalcones showed higher affinity for Aβ(1-42) aggregates than did (99m)Tc complexes. In sections of brain tissue from an animal model of AD, the four Re chalcones intensely stained β-amyloid plaques. In biodistribution experiments using normal mice, (99m)Tc-BAT-chalcone ([(99m)Tc]17) displayed high uptake in the brain (1.48% ID/g) at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.17% ID/g at 60 min), a highly desirable feature for an imaging agent. [(99m)Tc]17 may be a potential probe for imaging β-amyloid plaques in Alzheimer's brains.
The support of thin windows for X-ray proportional counters (1973)

A theoretical method is given for calculating the amount of support required for pressurized membranes of large breadth-to-thickness ratios. This theory has use in the design of windows for soft X-ray proportional counters.
Recombinant Human Gamma Interferon Administered by Continuous Intravenous Infusion in Acute Myelogenous Leukemia and Myelodysplastic Syndromes (1993)

Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 x 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFN gamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 x 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 x 10(6) U/m2/day also could not complete a full course of rIFN gamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFN gamma plasma levels in patients who tolerated a complete infusion were < 40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFN gamma at doses as low as 2 x 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 x 10(6) U/m2/day.
Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two different serotype specificities. (1995)

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. We analyzed dengue virus-specific CD8+ CD4- CTL at the clonal level to further understand the role of CD8+ CTL in dengue virus infections. Dengue virus-specific CD8+ CTL clones were established from lymphocytes of a dengue 4-immune adult. Three patterns of dengue serotype specificities were identified: 1) specific for dengue 4, 2) cross-reactive for dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four dengue virus serotypes. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone were further analyzed. All four of the clones were HLA-B35 restricted and recognized NS3. The epitopes were mapped to amino acids (aa) 483 to 618 of NS3. The epitope was then defined by using synthetic peptides. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone recognized the same peptide (TPEGIIPTL) encompassing aa 500 to 508 of dengue 4 NS3. The peptide encompassing aa 500-508 of dengue 2 NS3 was recognized by a dengue 2/dengue 4 cross-reactive clone but was not recognized by the dengue 4-specific clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clones used different TCR. These results indicate that CD8+ CTL clones that use different TCR and demonstrate two distinct serotype specificities recognize the same 9-mer peptide in the context of HLA-B35.
Topic Modeling for Short Texts with Auxiliary Word Embeddings (2016)

For many applications that require semantic understanding of short texts, inferring discriminative and coherent latent topics from short texts is a critical and fundamental task. Conventional topic models largely rely on word co-occurrences to derive topics from a collection of documents. However, due to the length of each document, short texts are much more sparse in terms of word co-occurrences. Data sparsity therefore becomes a bottleneck for conventional topic models to achieve good results on short texts. On the other hand, when a human being interprets a piece of short text, the understanding is not solely based on its content words, but also her background knowledge (e.g., semantically related words). The recent advances in word embedding offer effective learning of word semantic relations from a large corpus. Exploiting such auxiliary word embeddings to enrich topic modeling for short texts is the main focus of this paper. To this end, we propose a simple, fast, and effective topic model for short texts, named GPU-DMM. Based on the Dirichlet Multinomial Mixture (DMM) model, GPU-DMM promotes the semantically related words under the same topic during the sampling process by using the generalized Polya urn (GPU) model. In this sense, the background knowledge about word semantic relatedness learned from millions of external documents can be easily exploited to improve topic modeling for short texts. Through extensive experiments on two real-world short text collections in two languages, we show that GPU-DMM achieves comparable or better topic representations than state-of-the-art models, measured by topic coherence. The learned topic representation leads to the best accuracy in text classification task, which is used as an indirect evaluation.
Synthesis, Characteristics and Potential Application of Poly(β-Amino Ester Urethane)-Based Multiblock Co-Polymers as an Injectable, Biodegradable and pH/Temperature-Sensitive Hydrogel System (2012)

Physical polymeric hydrogels have significant potential for use as injectable depot drug/protein-delivery systems. In this study, a series of novel injectable, biodegradable and pH/temperature-sensitive multiblock co-polymer physical hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PEU) was synthesized by the polyaddition between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of PEG and a synthesized monomer BTB (or ETE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized co-polymers were characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and gel-permeation chromatography. Aqueous solutions of the co-polymers showed a sol-to-gel phase transition with increasing pH and a gel-to-sol phase transition with increasing temperature. The gel regions covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the molecular weight of PEG, PEG/PEU ratio and co-polymer solution concentration. A gel formed rapidly in situ after injecting the co-polymer solution subcutaneously into SD rats and remained for more than 2 weeks in the body. The cytotoxicity tests confirmed the non-cytotoxicity of this co-polymer hydrogel. The controlled in vitro release of the model anticancer drug, doxorubicin, from this hydrogel occurred over a 7-day period. This hydrogel is a potential candidate for biomedical applications and drug/protein-delivery systems.
Characterization of Calculus Matrix Calcification Nucleator (1979)

The nucleator of dental calculus matrix calcification, in vitro, was analyzed. Attention focused on proteolipid singularity, amino acid composition and related polarity, and phospholipid components. The data were compared to those of the nucleator of Bacterionema matruchotii calcification.
Deformation of Progressively Cracking Partially Prestressed Concrete Beams (1992)

Deflections of partially prestressed concrete beams are analyzed on the basis of bending theory with plane cross sections, taking into account not only plasticity of steel and nonlinearity of concrete in compression, but also the tensile strain softening of concrete. However, their effect is not very large and is much less than found in a previous analysis of nonprestressed concrete beams. The effect of tensile strain softening is found to be significant only in the initial post-cracking response and vanish near the ultimate load. The effect of tension stiffening of steel due to the surrounding concrete and the associated bond slip is neglected, since the discrepancy from test data which could be ascribed to this phenomenon is quite small and adequate agreement with tests in the initial post-cracking stage is found without tension stiffening. Comparisons are also made with the I-effective method of Branson and Trost, although generally these predictions are softer than measured and become unacceptable near the ultimate load. Comparisons of calculations as well as measurements between beams with bonded and unbonded reinforcement show a relatively small difference.
A novel analytical method for in vivo phosphate tracking (2006)

Genetically-encoded fluorescence resonance energy transfer (FRET) sensors for phosphate (P(i)) (FLIPPi) were engineered by fusing a predicted Synechococcus phosphate-binding protein (PiBP) to eCFP and Venus. Purified fluorescent indicator protein for inorganic phosphate (FLIPPi), in which the fluorophores are attached to the same PiBP lobe, shows P(i)-dependent increases in FRET efficiency. FLIPPi affinity mutants cover P(i) changes over eight orders of magnitude. COS-7 cells co-expressing a low-affinity FLIPPi and a Na(+)/P(i) co-transporter exhibited FRET changes when perfused with 100 microM P(i), demonstrating concentrative P(i) uptake by PiT2. FLIPPi sensors are suitable for real-time monitoring of P(i) metabolism in living cells, providing a new tool for fluxomics, analysis of pathophysiology or changes of P(i) during cell migration.
On the chemical mechanism of gastric secretion (1905)

Abstract It has long been known that the introduction of certain substances into the stomach provoke a secretion of gastric juice. This is regarded as in no sense depending upon mere mechanical stimulation of the mucous membrane, and it has been thought that the nervous mechanism of the gastric glands may be susceptible to certain local chemical stimuli. On the analogy of what has been held to be the mechanism at work in the secretion of pancreatic juice by Bayliss and Starling, it is probable that, in the process of absorption of digested food in the stomach, a substance may be separated from the cells of the mucous membrane which, passing into the blood or lymph, later stimulates the secretory cells of the stomach to functional activity. The following observations support this view:—
CAR T-cell intrinsic PD-1 checkpoint blockade: A two-in-one approach for solid tumor immunotherapy (2016)

PD-L1/2 expression in solid tumors inhibits chimeric antigen receptor (CAR) T-cell efficacy. A PD-1 dominant negative receptor expressed in CAR T cells provides cell-intrinsic checkpoint blockade and augments antitumor efficacy. A combinatorial immunotherapeutic strategy of combining CAR T cells with checkpoint blockade is a promising treatment approach for solid tumors.
Boundary Analysis for H2 Production by Fermentation: July 2001--September 2004 (2005)

This report, prepared for DOE's Hydrogen, Fuel Cells & Infrastructure Technologies Program, presents a boundary analysis for the production of hydrogen via fermentation of glucose or other carbohydrates. The Program's hydrogen production cost target goals cannot be met due to the high feedstock cost. The potential for lower-cost sugars to meet cost targets should be investigated.