gebhart/patrepeval huggingface dataset:
Characterisation of a series of human immunodeficiency virus isolates derived sequentially from a single patient (1991)

Five HIV-1 isolates were obtained sequentially from a single seropositive individual during the later stages of AIDS. Four of these isolates were adapted to grow in a continuous human T-lymphocytic cell line. Comparative biological and biochemical studies of the virus isolates were made using persistently infected cultures or virus derived from these systems respectively. The data obtained clearly shows that viruses with different biological properties can be isolated from the same individual at different times during the course of clinical AIDS.
A Rapid Gas Chromatographic Analysis of Diastereomeric Diamines (1975)

Derivatization of mixtures of bis(4-aminocyclohexyl)methane (PACM) and 2,2-bis(4-aminocyclohexyl)propane (PACP) with N,N-dimethylformamide dimethylacetal produces volatile and thermally stable N-dimethylaminomethylene derivatives which can be analyzed directly by gas chromatography without prior work-up. These derivatives yield well-resolved peaks on a Poly A-103 column. Analyses of the diamine mixtures give results with a standard deviation of less than 1 percent which are in good agreement with other standard methods.
Dietary Phytoestrogens Have Anti-Inflammatory Activity in a Guinea Pig Model of Asthma (2000)

Phytoestrogens are a normal constituent of soy protein and have been shown to have anti-inflammatory activity in various in vitro and in vivo models. The present study was designed to determine if a diet enriched in the phytoestrogen isoflavones, genistin and daidzin, would alter the antigen-induced cellular infiltration, particularly eosinophilia, characteristic of a guinea pig model of asthma. Throughout the duration of the study, guinea pigs were maintained on a control diet (standard guinea pig chow) or the same diet enriched in isoflavones. The animals were placed on the diet 2 weeks prior to active sensitization with ovalbumin (OA). Three weeks after sensitization, animals were challenged with OA aerosol. The cellular infiltration into the lung and protein and red blood cells (RBC) in the bronchoalveolar lavage fluid (BAL) were determined 17 hr later. In animals maintained on the control diet, OA aerosol challenge resulted in the expected increase in eosinophils in both the BAL and the lung tissue, an increase in neutrophils in the BAL, and an increase in protein and the number of RBC in the BAL. In contrast, in animals maintained on the isoflavone diet, the OA-induced eosinophilia in the lung tissue was significantly attenuated. In addition, OA challenge caused a greater increase in BAL protein in animals maintained on the isoflavone diet compared with animals on the control diet. Our results indicated that a diet enriched in isoflavones results in reduced antigen-induced eosinophilia in the lung in the guinea pig model of asthma. However, this beneficial anti-inflammatory effect of dietary phytoestrogens is accompanied by a potentially detrimental increase in antigen-induced leakage of protein into the airspace.
Enzymatic catalysis in nonaqueous solvents. (1988)

Subtilisin and alpha-chymotrypsin vigorously act as catalysts in a variety of dry organic solvents. Enzymatic transesterifications in organic solvents follow Michaelis-Menten kinetics, and the values of V/Km roughly correlate with solvent's hydrophobicity. The amount of water required by chymotrypsin and subtilisin for catalysis in organic solvents is much less than needed to form a monolayer on its surface. The vastly different catalytic activities of chymotrypsin in various organic solvents are partly due to stripping of the essential water from the enzyme by more hydrophilic solvents and partly due to the solvent directly affecting the enzymatic process. The rate enhancements afforded by chymotrypsin and subtilisin in the transesterification reaction in octane are of the order of 100 billion-fold; covalent modification of the active center of the enzymes by a site-specific reagent renders them catalytically inactive in organic solvents. Upon replacement of water with octane as the reaction medium, the specificity of chymotrypsin toward competitive inhibitors reverses. Both thermal and storage stabilities of chymotrypsin are greatly enhanced in nonaqueous solvents compared to water. The phenomenon of enzymatic catalysis in organic solvents appears to be due to the structural rigidity of proteins in organic solvents resulting in high kinetic barriers that prevent the native-like conformation from unfolding.
Expression of large amounts of neisserial porin proteins in Escherichia coli and refolding of the proteins into native trimers (1994)

Porins from different neisserial strains and species have been shown to have differences in both primary amino acid sequence and biophysical characteristics as observed by functional assays. A closer examination of how the changes in the primary amino acid sequence of Neisseria porin molecules correlate with these observed biophysical changes has been impeded by the inability to easily manipulate the cloned porin genes by modern molecular techniques and then obtain enough of the expressed modified porin protein to purify and use in these biophysical functional assays. In this report, we describe a method by which the genes encoding three different porin proteins, lacking their neisserial promoter and signal sequences, were cloned into an expression plasmid and transformed into Escherichia coli. Upon induction, large amounts of the porin proteins were produced. The expressed porin proteins were then manipulated to regenerate their native trimer structure and purified by standard protein chemistry. Sufficient purified recombinant porin protein was obtained for further antigenic as well as biophysical characterization. This sets the stage for the biophysical characterization of these neisserial porin proteins in more detail.
FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke (2005)

After three days of deliberation an advisory panel to the US Food and Drug Administration decided that the widely used cyclo-oxygenase-2 (COX 2) inhibitors rofecoxib (Vioxx), celecoxib (Celebrex), and valdecoxib (Bextra) all carry serious risks of heart attack and stroke and recommended that the FDA demand that the drugs carry “black box” warnings. But the panel did not recommend that the drugs be withdrawn from the market.

The panel was convened after Merck voluntarily withdrew rofecoxib (Vioxx) from the market on 30 September ( BMJ 2004;329: 816, 9 Oct) when it was found that the drug doubles the risk of heart attacks and strokes in patients who take it for 18 months or longer.

US media coverage of the panel's findings has been criticised by Dr Alastair Wood, the panel's chairman and associate dean at Vanderbilt University School of Medicine, Nashville. He said that the coverage was distorted because it focused on the fact that the panel had not recommended the drugs' withdrawal rather than on its finding of an increased risk of heart attack and stroke.

He said, “The general outcome [of the hearings] was greatly overrated in the US press. Two drugs were recommended for removal from the market by almost 50% of the …
Neocortical Dynamics and Human EEG Rhythms (1996)

1: Paul Nunez: Quantitative states of neocortex. 2: Paul Nunez: Towards a physics of neocortex. 3: Paul Nunez: Mind, brain and EEG. 4: Kenneth L. Pilgreen: Physiological, medical and cognitive correlates of EEG. 5: Fernando H. Lopes da Silva: Dynamics of electrical activity of the brain, local networks and modulating systems. 6: Richard B. Silberstein: Steady state visually evoked potentials, brain resonance and cognitive processes. 7: Alan Gevins and Brian Cutillo: Neuroelectric measures of mind. 8: Paul Nunez: Discrete linear systems of physics and brain. 9: Paul Nunez: Continuous linear systems of physics and brain. 10: Paul Nunez: Nonlinear phenomena and chaos. 11: Paul Nunez: Global contribution to EEG dynamics. 12: Paul Nunez: Experimental connections between EEG data and the global wave theory. 13: Lester Ingber: Statistical mechanics of multiple scales of neocortical interactions
Reducing Endoglin Activity Limits Calcineurin and TRPC‐6 Expression and Improves Survival in a Mouse Model of Right Ventricular Pressure Overload (2014)

These data establish endoglin as a regulator of TGF-β1 signaling by calcineurin and TRPC-6 in the RV and identify it as a potential therapeutic target to limit RV fibrosis and improve survival in RVPO, a common cause of death in cardiac and pulmonary disease.
Prognostic Value of Circulating KRAS2 Gene Mutations in Colorectal Cancer with Distant Metastases (2006)

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p&lt;0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to correlate with prognosis in this patient subgroup.
Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions (2009)

The common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure. This variability results in difficulty in making coherent sense of either immunopathogenesis or the role of various genetic abnormalities reported in the literature. The recent attempt to collate the varied complications in these conditions and to define particular clinical phenotypes has improved our understanding of these diseases. Once refined and confirmed by other studies, these definitions will facilitate improved accuracy of prognosis and better management of clinical complication. They may also provide a method of analysing outcomes as related to new immunopathological and genetic findings.
MS2Assign, automated assignment and nomenclature of tandem mass spectra of chemically crosslinked peptides (2003)

In a previous report (Young et al., Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 5802-5806), we provided a proof-of-principle for fold recognition of proteins using a homobifunctional amine-specific chemical crosslinking reagent in combination with mass spectrometry analysis and homology modeling. In this current work, we propose a systematic nomenclature to describe the types of peptides that are generated after proteolysis of crosslinked proteins, their fragmentation by tandem mass spectrometry, and an automated algorithm for MS/MS spectral assignment called "MS2Assign." Several examples are provided from crosslinked peptides and proteins including HIV-integrase, cytochrome c, ribonuclease A, myoglobin, cytidine 5-monophosphate N-acetylneuraminic acid synthetase, and the peptide thymopentin. Tandem mass spectra were obtained from various crosslinked peptides using post source decay MALDI-TOF and collision induced dissociation on a quadrupole-TOF instrument, along with their automated interpretation using MS2Assign. A variety of possible outcomes are described and categorized according to the number of modified lysines and/or peptide chains involved, as well as the presence of singly modified (dead-end) lysine residues. In addition, the proteolysis and chromatographic conditions necessary for optimized crosslinked peptide recovery are presented.
Metformin inhibits the development, and promotes the resensitization, of treatment-resistant breast cancer (2017)

Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors. Here, we present the important in vitro discovery that the development of MDR (in breast cancer cells) can be prevented, and that established MDR could be resensitized to therapy, by adjunct treatment with metformin. Metformin is prescribed globally to improve insulin sensitivity, including in those individuals with Type 2 Diabetes Mellitus (DM2). We demonstrate the effectiveness of metformin in resensitizing MDR breast cancer cell lines to their original treatment, and provide evidence that metformin may function through a mechanism involving post-translational histone modifications via an indirect histone deacetylase inhibitor (HDACi) activity. We find that metformin, at low physiological concentrations, reduces the expression of multiple classic protein markers of MDR in vitro and in preliminary in vivo models. Our demonstration that metformin can prevent MDR development and resensitize MDR cells to chemotherapy in vitro, provides important medical relevance towards metformin's potential clinical use against MDR cancers.
Direct observation of porous SiC formed by anodization in HF (1993)

A process for forming porous SiC from single-crystal SiC wafers has been demonstrated. Porous SiC can be fabricated by anodizing n-type 6H-SiC in HF under UV illumination. Transmission electron microscopy reveals pores of sizes 10–30 nm with interpore spacings ranging from ≊5 to 150 nm. This is the first reported direct observation of porous SiC formation.
Celecoxib for the Prevention of Sporadic Colorectal Adenomas (2006)

These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).
Cation interactions with polyamic acids (1989)

Abstract Polyamic acid films interact as ion‐exchange substrates for dilute aqueous cation solutions. Three conditions were evaluated: basic solutions which form soluble amic acid salts and dissolve the film, weakly acidic solutions which encourage classical weak acid cation exchange, and strongly acidic solutions which discourage exchange. Thermal treatment of the generated cationamate salts generally causes degradation of the polymer backbone. Furthermore, lead and copper react directly with the polyamic acid to yield surface‐bound salts, but tin and aluminum seem unreactive.
Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma (2013)

Our study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment.
Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction (2007)

The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients. The c statistic, however, may not be optimal in assessing models that predict future risk or stratify individuals into risk categories. In this setting, calibration is as important to the accurate assessment of risk. For example, a biomarker with an odds ratio of 3 may have little effect on the c statistic, yet an increased level could shift estimated 10-year cardiovascular risk for an individual patient from 8% to 24%, which would lead to different treatment recommendations under current Adult Treatment Panel III guidelines. Accepted risk factors such as lipids, hypertension, and smoking have only marginal impact on the c statistic individually yet lead to more accurate reclassification of large proportions of patients into higher-risk or lower-risk categories. Perfectly calibrated models for complex disease can, in fact, only achieve values for the c statistic well below the theoretical maximum of 1. Use of the c statistic for model selection could thus naively eliminate established risk factors from cardiovascular risk prediction scores. As novel risk factors are discovered, sole reliance on the c statistic to evaluate their utility as risk predictors thus seems ill-advised.
Inhibition of transformed cell growth and induction of cellular differentiation by pyroxamide, an inhibitor of histone deacetylase. (2001)

The findings suggest that pyroxamide may be a useful agent for the treatment of malignancy and that induction of p21/WAF1 in transformed cells by pyroxamide may contribute to the antitumor effects of this agent.
The Ocular Manifestations of Fabry's Disease: A Family Study. (1983)

The ocular manifestations of Fabry's disease are described in an affected homozygous male and a heterozygous female carrier (his mother). In addition, the features of this condition are reviewed and the differential diagnosis of the corneal changes (verticillata or thesaurismosis) is discussed.
Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women (2009)

The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.
“Physiological genomics”: mutant screens in zebrafish (1998)

Large-scale mutagenesis screens have proved essential in the search for genes that are important to development in the fly, worm, and yeast. Here we present the power of large-scale screening in a vertebrate, the zebrafish Danio rerio, and propose the use of this genetic system to address fundamental questions of vertebrate developmental physiology. As an example, we focus on zebrafish mutations that reveal single genes essential for normal development of the cardiovascular system. These single gene mutations disrupt specific aspects of rate, rhythm, conduction, or contractility of the developing heart.
Applications of microwaves in biological sciences (2003)

Microwave irradiation can alter the rate of enzyme-catalysed reactions, although the role of any non-thermal factors in such processes is controversial. While the studies in aqueous buffers have been under-standably limited to thermostable enzymes, higher stability of enzymes in anhydrous media allows the use of a variety of enzymes. The microwave-assisted applications described in this review include use of lipases for esterification and transesterification reac-tions, protease for peptide synthesis and again, use of two well-known proteases, a-chymotrypsin and subtil-isin Carlsberg in esterification and transesterifica ion reactions respectively. In the last system, it has been shown that the so-called non-thermal effects increase the reaction rates by 2-5 fold at all water-activity levels.
Assembly of a Chromosomal Replication Machine: Two DNA Polymerases, a Clamp Loader, and Sliding Clamps in One Holoenzyme Particle. (1995)

The Escherichia coli replicase, DNA polymerase III holoenzyme, derives its processivity from the beta subunit sliding clamp that encircles DNA and tethers the replicase to the template. The beta dimer is assembled around DNA by the gamma complex clamp loader in an ATP-dependent reaction. In this report, the essential contact between the clamp loader and beta is identified as mediated through the delta subunit of the gamma complex. The delta subunit appears to contact the face of the beta dimer ring that contains the two C termini. Surprisingly, ATP is required for the gamma complex to bind beta, but not for delta to bind beta. This indicates that delta is buried in the gamma complex and suggests a role for ATP in exposing delta for interaction with beta. A protease protection assay has been developed to specifically probe the delta subunit within the gamma complex. The results of the assay are consistent with an ATP-induced conformational change in the gamma complex that alters the state of the delta subunit within it. The implication of these key features to the clamp loading mechanism of the gamma complex is discussed.
Measurement system for magneto-optic sensor materials (1984)

A system for the measurements of magneto-optic properties of IR-transparent materials is described. The system is designed for the characterisation of fibre optic magnetic field sensor materials. Measurement results on YIG-crystals are presented. The accuracy of Faraday rotation and light transmission measurements are +or-2 m rad and +or-2% respectively. Important features for the sensor characterisation are light beam scanning, temperature control and flexible magnetic field generation. A desktop computer is used for system control and data acquisition. The system is expected to be of great importance for future sensor developments.
Dendrimer-controlled one-pot synthesis of gold nanoparticles with a bimodal size distribution and their self-assembly in the solid state (2003)

Gold nanoparticles have been precipitated in the presence of a stiff polyphenylene dendrimer template with 16 thiomethyl groups on the outside. Powder X-ray diffraction analysis shows an average particle size of ∼3.7 nm; surprisingly, transmission electron microscopy (TEM) reveals a bimodal particle size distribution. Most of the small particles are single crystals and the large ones have multiple crystalline domains, as observed by high resolution TEM. The particles aggregate in the solid state due to the cross-linking ability of the dendrimer. They are reversibly soluble in chloroform and toluene for extended periods of time, and can be solution cast onto flat substrates. A strong plasmon band at 560 nm and a shoulder at ∼370 nm are observed in the UV/Vis spectrum of the material.