gebhart/patrepeval huggingface dataset:
Structural and Functional Analysis of Laninamivir and its Octanoate Prodrug Reveals Group Specific Mechanisms for Influenza NA Inhibition (2011)

The 2009 H1N1 influenza pandemic (pH1N1) led to record sales of neuraminidase (NA) inhibitors, which has contributed significantly to the recent increase in oseltamivir-resistant viruses. Therefore, development and careful evaluation of novel NA inhibitors is of great interest. Recently, a highly potent NA inhibitor, laninamivir, has been approved for use in Japan. Laninamivir is effective using a single inhaled dose via its octanoate prodrug (CS-8958) and has been demonstrated to be effective against oseltamivir-resistant NA in vitro. However, effectiveness of laninamivir octanoate prodrug against oseltamivir-resistant influenza infection in adults has not been demonstrated. NA is classified into 2 groups based upon phylogenetic analysis and it is becoming clear that each group has some distinct structural features. Recently, we found that pH1N1 N1 NA (p09N1) is an atypical group 1 NA with some group 2-like features in its active site (lack of a 150-cavity). Furthermore, it has been reported that certain oseltamivir-resistant substitutions in the NA active site are group 1 specific. In order to comprehensively evaluate the effectiveness of laninamivir, we utilized recombinant N5 (typical group 1), p09N1 (atypical group 1) and N2 from the 1957 pandemic H2N2 (p57N2) (typical group 2) to carry out in vitro inhibition assays. We found that laninamivir and its octanoate prodrug display group specific preferences to different influenza NAs and provide the structural basis of their specific action based upon their novel complex crystal structures. Our results indicate that laninamivir and zanamivir are more effective against group 1 NA with a 150-cavity than group 2 NA with no 150-cavity. Furthermore, we have found that the laninamivir octanoate prodrug has a unique binding mode in p09N1 that is different from that of group 2 p57N2, but with some similarities to NA-oseltamivir binding, which provides additional insight into group specific differences of oseltamivir binding and resistance.
Cryosurgery (2000)

Cryosurgery is a surgical technique that employs freezing to destroy undesirable tissue. Developed first in the middle of the nineteenth century it has recently incorporated new imaging technologies and is a fast growing minimally invasive surgical technique. A historical review of the field of cryosurgery is presented, showing how technological advances have affected the development of the field. This is followed by a more in-depth survey of two important topics in cryosurgery: (a) the biochemical and biophysical mechanisms of tissue destruction during cryosurgery and (b) monitoring and imaging techniques for cryosurgery.
ANIMAL CALORIMETRY (1921)

CHART 1.The rise in calories above the basal metabolism which follows the ingestion of various metabolites.
Evaluation of subsampling and fixation procedures used for counting rumen protozoa (1984)

Total numbers of protozoa can be significantly lower in rumen fluid than in whole rumen contents, depending on the time of sampling and the procedure used to separate the fluid and solid fractions. Moreover, generic distribution in rumen fluid was significantly affected in all cases tested. The percentage of Entodinium spp. increased, whereas percentages of Diplodinium spp. and Ophryoscolex spp. decreased. Microscopic observation of fresh and fixed rumen contents did not indicate any marked attachment of protozoa to particulate matter. In addition, dilution of whole rumen contents with water, 5 mM sucrose, or 0.1% Tween 80 before fixation did not affect total numbers or generic composition of protozoa. It was thus concluded that attachment to feed particles is probably not a problem in counting procedures. Blending of whole rumen contents to facilitate subsampling caused a decrease in numbers of protozoa. The concentration of formaldehyde used for preservation of rumen contents, 4, 10, or 18.5%, did not affect the total count.
FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration (2003)

ibroblast migration depends, in part, on activation of FAK and cellular interactions with tenascin-C (TN-C).Consistent with the idea that FAK regulates TN-C, migration-defective FAK-null cells expressed reduced levels of TN-C.Furthermore, expression of FAK in FAK-null fibroblasts induced TN-C, whereas inhibition of FAK activity in FAK-wild-type cells had the opposite effect.Paired-related homeobox 1 ( Prx1 ) encodes a homeobox transcription factor that induces TN-C by interacting with a binding site within the TN-C promoter, and it also promotes fibroblast migration.Therefore, we hypothesized that FAK regulates TN-C by controlling the DNA-binding activity of Prx1 and/or by inducing Prx1 expression.Prx1-homeodomain binding site F complex formation observed with FAK-wild-type fibroblasts failed to occur in FAK-null fibroblasts, yet expression of Prx1 in these cells induced TN-C promoter activity.Thus, FAK is not essential for Prx1 DNA-binding activity.However, activated FAK was essential for Prx1 expression.Functionally, Prx1 expression in FAK-null fibroblasts restored their ability to migrate toward fibronectin, in a manner that depends on TN-C.These results appear to be relevant in vivo because Prx1 and TN-C expression levels were reduced in FAK-null embryos.This paper suggests a model whereby FAK induces Prx1, and subsequently the formation of a TN-C-enriched ECM that contributes to fibroblast migration.
Botulinum toxin in clinical practice (2004)

Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications.
Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota (2015)

Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
Superomniphobic Magnetic Microtextures with Remote Wetting Control (2012)

Universal remote control of wetting behavior enabling the transition from a superomniphobic to an omniphilic wetting state in an external magnetic field via the alternation of reentrant curvature of a microstructured surface is demonstrated. This reconfigurable microtexture made of Ni micronails repels water, water-surfactant solutions, and practically all organic liquids, whereas it gets wetted by all of these liquids after a magnetic field pulse is applied.
Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children (2011)

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.
Reduction of aluminum levels in dialysis fluids through the development and use of accurate and sensitive analytical methodology. (1987)

Various analytical methods of determining the aluminum content of CAPD (continuous ambulatory peritoneal dialysis) solutions and associated raw materials were developed and compared. The methods include two graphite furnace atomic absorption procedures and an aluminum-lumogallion fluorescence technique that can quantitate aluminum in CAPD solution at, and in some cases below, the 1-μg/liter level with good accuracy and precision. These methods were then used to examine the possible contributions to aluminum content from all aspects of the production of CAPD solutions at Travenol Laboratories, Inc. The major source of aluminum to the low, but measurable, levels in CAPD solutions was lactic acid. With the use of USP grade or equivalent ingredients, especially a low-aluminum-content lactic acid, these solutions can be prepared with aluminum levels below 10 μg/liter.
Hypolipidemic effects of hydrolyzed xyloglucan (1997)

Abstract Xyloglucan is found in the primary cell walls of higher plants, where it plays important biological roles. It also exists in certain seeds, for example tamarind, as a reserve polysaccharide. Some xyloglucan oligosaccharides possess plant growth promotion activity. We prepared hydrolyzed xyloglucan from the tamarind seed xyloglucan using endo‐(1 → 4)‐ β ‐glucanase and examined its effects on lipid metabolism in rats fed a high fat diet. Among the plasma lipids, total lipid, cholesterol, triglyceride and β ‐ lipoprotein were each reduced 14 ‐ 17% by hydrolyzed xyloglucan. Hydrolyzed xyloglucan significantly reduced both adipose tissue weight and plasma GOT. Among the hepatic lipids, total lipid, cholesterol, triglyceride and phospholipid were significantly reduced by hydrolyzed xyloglucan. These hypolipidemic effects may be important for the treatment and prevention of geriatric diseases, including diabetes and cardiac disorders.
Single Molecules Observed by Near-Field Scanning Optical Microscopy (1993)

Individual carbocyanine dye molecules in a sub-monolayer spread have been imaged with near-field scanning optical microscopy. Molecules can be repeatedly detected and spatially localized (to approximately lambda/50 where lambda is the wavelength of light) with a sensitivity of at least 0.005 molecules/(Hz)(1/2) and the orientation of each molecular dipole can be determined. This information is exploited to map the electric field distribution in the near-field aperture with molecular spatial resolution.
Constructing the Call Graph of a Program (1979)

The proliferation of large software systems written in high level programming languages insures the utility of analysis programs which examine interprocedural communications. Often these analysis programs need to reduce the dynamic relations between procedures to a static data representation. This paper presents one such representation, a directed, acyclic graph named the call graph of a program. We delineate the programs representable by an acyclic call graph and present an algorithm for constructing it using the property that its nodes may be linearly ordered. We prove the correctness of the algorithm and discuss the results obtained from an implementation of the algorithm in the PFORT Verifier [1].
Early Apoptotic Cells (ApoCell) As Prophylaxis of Graft-Versus-Host Disease Is Safe and Effective: 1 Year Follow-up and Mechanism of Action (2015)

Apoptotic cells infusion (ApoCell, by Enlivex Ltd) is a novel cellular therapy that was found to be effective in a variety of mouse models of autoimmune diseases. ApoCell was tested in humans in addition to cyclosporine and methotrexate, as prophylaxis of graft-versus-host disease (GVHD) in HLA-matched myeloablative allogeneic bone marrow transplantation (alloBMT) from a related donor. We conducted a phase I//IIa clinical trial where 13 patients (median age, 37 years; range, 20-59 years) with advanced hematologic malignancies that received conventional myeloablation were treated with 35, or 70, or 140, or 210x106 cell/kg of donor ApoCell, on day -1 of transplantation (Mevorach et al. BBMT 2014). We now report the summary of biomarkers measurement (ELISA) as a correlation to the clinical grading. These include serum levels of Il-1b, IL-2RA, IL-6, IL-7, IL-8, IL-15, TNF-R1, and HGF (hepatic growth factor). We further report the ApoCell clearance following the infusion, using short tandem repeats (str) and the tolerogenic effect of ApoCell on immature dendritic cells (iDC) exposed to maturation stimuli. In addition, a 1 year follow-up and a clinical comparison to matched historical controls were evaluated. The results show an excellent correlation between biomarkers to clinical grading with a distinctive pattern between high-grade (III-IV) to low grade GVHD. A rapid clearance of the infused ApoCell that disappears from circulation within few hours and ApoCell dose-dependent tolerogenic effect on iDC (p<0.001) were observed. The 1 year overall survival rate was 62% with a non-relapse survival rate of 89% (100% for the two higher cohorts), and a significant (p<0.05) lower occurrence (23% in total and 0% in the two higher dosages) of high-grade GVHD (II-IV) in comparison to historical controls. These results suggest that single-infusion high-dose donor early apoptotic cells in HLA-matched myeloablative alloBMT may be a safe and effective prophylaxis for acute GVHD (clinicaltrials.gov no. NCT00524784).
Thermo and pH stable ATP-independent chaperone activity of heat-inducible Hsp70 fromPennisetum glaucum (2010)

Heat shock proteins (Hsps) are a class of molecular chaperones that play an essential role in preserving cellular functions under stressful conditions. The over production of recombinant proteins often causes cellular stress that results in aggregation/misfolding of proteins, which sometimes leads to the formation of inclusion bodies. Here we report the cloning and characterization of heat-inducible PgHsp70 from Pennisetum glaucum, a heat and drought tolerant plant that showed stability and chaperone activity at elevated temperatures. The predicted amino acid sequence of PgHsp70 revealed a high homology with Hsp70 from other plants, and the overall 3D structure homology modeling is similar to that of the constitutively expressed bovine cytosolic Heat Shock Cognate (HSC)-70. The purified recombinant protein had an apparent molecular mass of 70 kDa and displayed optimal chaperone activity at 50 degrees C, and pH 8.0. Under these conditions, the T(1/2) of PgHsp70 increased from 10 to 15 h in the presence of glycerol. The PgHsp70 exhibited a higher chaperone activity towards glutamate dehydrogenase than alcohol dehydrogenase. The expression of recombinant carbonic anhydrase (CA) in E. coli in a catalytically active soluble form rather than in inclusion bodies was made feasible by co-expression of PgHsp70. Circular dichroism (CD) studies of the recombinant PgHsp70 did not reveal any discernible changes in the alpha-helix content, with increase in temperature from 35 to 85 degrees C, thus suggesting a critical role of alpha-helix content in maintaining the chaperone activity.
Linker insertion mutagenesis of the human immunodeficiency virus reverse transcriptase expressed in bacteria: definition of the minimal polymerase domain. (1989)

A plasmid construct expressing the p66 version of the human immunodeficiency virus reverse transcriptase as a bacterial fusion protein was subjected to in vitro mutagenesis, and the resulting variant proteins were assayed to define the locations of the two major enzymatic activities. The DNA polymerase activity was localized to the N-terminal portion of the protein; mutations altering or eliminating the C-terminal portion had little or no effect on that activity. The results suggest that, in contrast with previous reports, the p51 subunit found in virions should exhibit DNA polymerase activity. Mutations in many parts of the protein eliminated RNase H activity, suggesting that several areas are needed for proper folding and generation of that activity.
A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. (1992)

The surface of streptococci presents an array of different proteins, each designed to perform a specific function. In an attempt to understand the early events in group A streptococci infection, we have identified and purified a major surface protein from group A type 6 streptococci that has both an enzymatic activity and a binding capacity for a variety of proteins. Mass spectrometric analysis of the purified molecule revealed a monomer of 35.8 kD. Molecular sieve chromatography and sodium dodecyl sulfate (SDS)-gel electrophoresis suggest that the native conformation of the protein is likely to be a tetramer of 156 kD. NH2-terminal amino acid sequence analysis revealed 83% homology in the first 18 residues and about 56% in the first 39 residues with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of eukaryotic or bacterial origin. This streptococcal surface GAPDH (SDH) exhibits a dose-dependent dehydrogenase activity on glyceraldehyde-3-phosphate in the presence of beta-nicotinamide adenine dinucleotide both in its pure form and on the streptococcal surface. Its sensitivity to trypsin on whole organism and its inability to be removed with 2 M NaCl or 2% SDS support its surface location and tight attachment to the streptococcal cell. Affinity-purified antibodies to SDH detected the presence of this protein on the surface of all M serotypes of group A streptococcal tested. Purified SDH was found to bind to fibronectin, lysozyme, as well as the cytoskeletal proteins myosin and actin. The binding activity to myosin was found to be localized to the globular heavy meromyosin domain. SDH did not bind to streptococcal M protein, tropomyosin, or the coiled-coil domain of myosin. The multiple binding capacity of the SDH in conjunction with its GAPDH activity may play a role in the colonization, internalization, and the subsequent proliferation of group A streptococci.
Modulation of neural network activity in vitro by cyclothiazide, a drug that blocks desensitization of AMPA receptors (1995)

To determine whether AMPA receptor channel desensitization has a physiological role in shaping network activity by modulating signal transmission through excitatory circuits, we examined the effects of cyclothiazide (CYT), the most potent known blocker of AMPA receptor desensitization, on the behavior of an endogenously active neural system in vitro, the brainstem network generating rhythmic respiratory oscillations in neonatal rat medullary slices. Bath application of 100 microM CYT significantly increased the frequency of endogenously generated rhythm and increased the amplitude of the circuit output [i.e., discharge of hypoglossal (XII) respiratory motoneurons]. Local application of CYT within the XII motor nucleus produced a concentration-dependent increase (up to 35%) in amplitude of the motoneuron population discharge as well as an increase in the peak current (23%) and total charge transfer of the rhythmic inspiratory synaptic drive (33%) to individual XII motoneurons. CYT also acted postsynaptically to increase the amplitude of spontaneous EPSCs in motoneurons. In addition, CYT produced a profound, long-term augmentation of network frequency and motor output that may be secondary to block of desensitization. These results suggest that AMPA receptor desensitization has functionally significant effects on the temporal behavior and output of the rhythmic, respiratory neural network, and, by extrapolation, on other integrative actions of the mammalian CNS.
Genetic Cholesteryl Ester Transfer Protein Deficiency Is Extremely Frequent in the Omagari Area of Japan (1997)

Low levels of HDL cholesterol have been clearly demonstrated to be associated with an increased incidence of coronary heart disease, strongly suggesting that HDL particles have an antiatherogenic function. However, little information has been available concerning the atherogenicity of a marked hyperalphalipoproteinemia (HALP). There is no agreement about whether plasma cholesteryl ester transfer protein (CETP) deficiency is associated with an antiatherogenic state or not, although this disorder was reported to be one of the major causes of marked HALP. In the current study, we have found a unique area (Omagari City, Akita Prefecture, Japan) where CETP deficiency caused by a G-to-A mutation at the 5' splice donor site of intron 14 in the CETP gene is extremely frequent. In Omagari City, the mutation was detected more than 20 times more frequently and the prevalence of a marked HALP with plasma HDL cholesterol > or = 2.58 mmol/L (100 mg/dL) was 5 to 10 times higher than in other areas of Japan. This discovery has made it possible to perform a large population-based study concerning the atherogenicity of a marked elevation of HDL cholesterol in a genetically more homogeneous population. There was a statistically significant U-shaped relationship between HDL cholesterol levels and the incidence of ischemic changes in electrocardiograms. In cases of HDL cholesterol < 1.81 mmol/L (70 mg/dL), the incidence increased in proportion to the levels of HDL cholesterol. The frequency of the CETP gene mutation was higher in patients with coronary heart disease than in healthy control subjects. In subjects aged > 80 years, the prevalence of both marked HALP and the intron 14 splicing defect was significantly lower than in the younger generation. The current study indicated for the first time that a marked HALP caused by CETP gene mutation may not represent a longevity syndrome, suggesting the importance of reevaluation of the clinical significance and pathophysiology of a marked HALP.
A Possible Mechanism of Alkene/Alkane Production (1981)

Alkene/alkane ratios have been used extensively as indicators of oil-shale retorting conditions. Jacobson, Decora, and Cook (1) developed a retorting index that relates the ethene/ethane ratio to temperature, and Campbell and coworkers related ethene/ethane and propene/propane ratios (2), C7 to C12 1-alkene/n-alkane ratios (3), and total 1-alkene/n-alkane ratios (4) to the logarithm of the heating rate during retorting. In addition, Raley (5) worked out a relationship between the ethene/ethane and propene/propane ratios and the yield loss in the combustion retorts at Lawrence Livermore National Laboratory (LLNL). Uden et al. (6) reported how the C2 to C5 alkene/alkane ratios change with a change in the amount of the oxygen present during retorting. Finally, Burnham (7) demonstrated that the ethene/ethane ratios are related to the oil-cracking temperature. Our objective was to clarify the reaction mechanisms that determine the observed alkene/alkane ratios under various conditions, and the results are reported here. When oil