gebhart/patrepeval huggingface dataset:
Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeats (2009)

Abstract Background Mesothelin is a 40 kDa protein present on the surface of normal mesothelial cells and overexpressed in many human tumours, including mesothelioma and ovarian and pancreatic adenocarcinoma. It forms a strong and specific complex with MUC16, which is also highly expressed on the surface of mesothelioma and ovarian cancer cells. This binding has been suggested to be the basis of ovarian cancer metastasis. Knowledge of the structure of this protein will be useful, for example, in building a structural model of the MUC16-mesothelin complex. Mesothelin is produced as a precursor, which is cleaved by furin to produce the N-terminal half, which is called the megakaryocyte potentiating factor (MPF), and the C-terminal half, which is mesothelin. Little is known about the function of mesothelin and there is no information on its possible three-dimensional structure. Mesothelin has been reported to be homologous to the deafness-related inner ear proteins otoancorin and stereocilin, for neither of which the three-dimensional structure is known. Results The BLAST and PSI-BLAST searches confirmed that mesothelin and mesothelin precursor proteins are remotely homologous to stereocilin and otoancorin and more closely homologous to the hypothetical protein MPFL (MPF-like). Secondary structure prediction servers predicted a predominantly helical structure for both mesothelin and mesothelin precursor proteins and also for stereocilin and otoancorin. Three-dimensional structure prediction servers INHUB and I-TASSER produced structural models for mesothelin, which consisted of superhelical structures with ARM-type repeats in conformity with the secondary structure predictions. Similar ARM-type superhelical repeat structures were predicted by 3D-PSSM server for mesothelin precursor and for stereocilin and otoancorin proteins. Conclusion The mesothelin superfamily of proteins, which includes mesothelin, mesothelin precursor, megakaryocyte potentiating factor, MPFL, stereocilin and otoancorin, are predicted to have superhelical structures with ARM-type repeats. We suggest that all of these function as superhelical lectins to bind the carbohydrate moieties of extracellular glycoproteins.
Digital PCR (1999)

The identification of predefined mutations expected to be present in a minor fraction of a cell population is important for a variety of basic research and clinical applications. Here, we describe an approach for transforming the exponential, analog nature of the PCR into a linear, digital signal suitable for this purpose. Single molecules are isolated by dilution and individually amplified by PCR; each product is then analyzed separately for the presence of mutations by using fluorescent probes. The feasibility of the approach is demonstrated through the detection of a mutant ras oncogene in the stool of patients with colorectal cancer. The process provides a reliable and quantitative measure of the proportion of variant sequences within a DNA sample.
Na+-H+ exchange in gastric glands as measured with a cytoplasmic-trapped, fluorescent pH indicator. (1984)

We have used the pH-sensitive, fluorescent, cytoplasmic-trapped dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) to identify Na+-H+ exchange in gastric glands isolated from rabbit stomachs by high-pressure perfusion and collagenase digestion. The fluorescence of BCECF-loaded glands was calibrated in terms of cytosolic pH (pHc) by permeabilizing the cell membranes and titrating the extracellular solution to different pH values. In one set of experiments in Cl--free solutions, glands were treated with 0.1 mM ouabain for 45 min to increase cellular cytosolic molar sodium ion concentration [( Na+]c) to high levels. Subsequent suspension of these cells in a Na+-free Ringer's solution (to generate [Na+]c greater than [Na+]o) caused cells to acidify rapidly (t1/2 approximately equal to 60 sec) from pHc approximately equal to 7.15 to pHc approximately equal to 6.55. Subsequent addition of 100 mM Na+ or Li+, but not K+, caused cells rapidly to increase pHc (t1/2 approximately equal to 30 sec) toward the control value. These changes of pHc were blocked when ouabain-treated glands had been preequilibrated for 10 min with 1 mM amiloride, and this block was overcome by adding 10 microM monensin (an ionophore that artificially exchanges Na+ for H+). In another set of experiments in Cl--containing Ringer's solution, glands were acid-loaded by treatment with 30 mM NH4Cl for 4 min, followed by washing the NH4Cl from the solutions. Under these conditions, pHc decreased from 7.02 to approximately equal to 6.5; subsequent alkalinization of cells back to control pHc was stimulated by Na+ (t1/2 approximately equal to 60 sec), but not K+, and was inhibited by 1 mM amiloride. This amiloride block also was overcome by further addition of 10 microM monensin. We conclude that gastric glands contain a Na+-H+ exchanger that appears independent of Cl-, not activated by K+, and blocked by 1 mM amiloride. This exchanger is likely localized to the serosal membrane of gland cells. Na+-H+ exchange may play an important role in regulation of pHc in oxyntic and chief cells exposed to high luminal acidity, where back diffusion of H+ into cells may occur at rapid rates.
Mathematical model to predict the number of nodes in an ROBDD (2004)

This paper analyses and describes the relation between the size of a Boolean function and the number of nodes in its ROBDD representation. Knowing the number of variables and the number of product terms of a Boolean function, we can predict the number of nodes in its reordered binary decision diagram (ROBDD) without building the BDD. A mathematical model for this prediction has been developed. This model can be used to find the maximum number of nodes that can be produced for a given number of variables. The model can also be used to find the number of product terms above which the ROBDD is reduced to 1 node only. We demonstrate that the predictions using this model are quite promising, fast and easy to implement.
Estudio in silico de propiedades moleculares del ceftaroline (2011)

Background: Ceftaroline is the latest developed cephalosporin. Its molecular modeling can help deepening the structural bases underpinning its pharmacological characteristics. Objective: to model structural and electronic properties of the ceftaroline. Method: a theoretical study using quantum mechanics methods was conducted in order to model the structure and electronic properties of the ceftaroline. Molecular geometry was optimized with semiempirical calculations according to parameterized model # 3. Molecular properties were calculated according to the Density Functional Theory. Densities of atomic charges and orbital borders were analyzed and compared to the ceftobiprole modeling. Results: the ceftaroline has a more compact and less elongated three-dimensional structure than the ceftobiprole. The positive charges densities on the carbonyl carbon are slightly lower than their equivalents in the ceftobiprole. Conclusions: an ethyl presence in the ceftaroline oxime group modifies its spatial configuration which makes it more compact and may influence its antibacterial action.
Cardiac dynamics: Alternans and arrhythmogenesis (2016)

Pre-existing heterogeneities present in cardiac tissue are essential for maintaining the normal electrical and mechanical functions of the heart. Exacerbation of such heterogeneities or the emergence of dynamic factors can produce repolarization alternans, which are beat-to-beat alternations in the action potential time course. Traditionally, this was explained by restitution, but additional factors, such as cardiac memory, calcium handling dynamics, refractory period restitution, and mechano-electric feedback, are increasingly recognized as the underlying causes. The aim of this article is to review the mechanisms that generate cardiac repolarization alternans and convert spatially concordant alternans to the more arrhythmogenic spatially discordant alternans. This is followed by a discussion on how alternans generate arrhythmias in a number of clinical scenarios, and concluded by an outline of future therapeutic targets for anti-arrhythmic therapy.
Towards new leprosy and tuberculosis vaccines. (1987)

Leprosy and tuberculosis are chronic infectious diseases causing major global health problems, for which no effective control by vaccination has been achieved. Recent advances in biotechnology may facilitate the design of a new vaccine generation. In this paper the need for, and the potential of, leprosy and tuberculosis vaccines are discussed.
Binding, Internalization, and Intracellular Processing of Proteins Interacting with Recycling Receptors (1989)

We measured time-dependent concentration changes of human interferon-alpha 2a (IFN) and human tumor necrosis factor-alpha (TNF) bound at the plasma membrane and internalized by human lung alveolar carcinoma A549 cells in the presence of excess free ligand. Concentration changes for these two ligands were substantially different. We modified our compartmental kinetic model encompassing receptor synthesis and receptor loss (Myers, A. C., Kovach, J. S., and Vuk-Pavlović, S. (1987) J. Biol. Chem. 262, 6494-6499) to include receptor recycling. We solved analytically the equations of three variants of the model of receptor recycling. All parameters (rate constants) were identifiable when the data sets consisted of time-resolved concentrations of IFN and TNF at the cell surface and internalized by cells. By least squares fitting we derived the best fit values for the first order rate constants for internalization of the ligand-receptor complex, receptor recycling, turnover of free receptors, elimination of the ligand from cells, and the rate of insertion of free receptors into the membrane. The best fit to data for interactions of cells with IFN was obtained without inclusion of the term for recycling of receptors to the membrane. The simplest model including receptor recycling was necessary and sufficient for the fit to the respective data for TNF. These results demonstrate that the contribution of receptor recycling to the metabolism of the ligand and the receptor can be quantitated by compartmental modeling. Receptor recycling does not contribute to the kinetics of Type I IFN receptor in A549 cells. In contrast, recycling contributes significantly to endocytosis mediated by the TNF receptor.
Effects of antipsychotics on fat deposition and changes in leptin and insulin levels (2003)

Patients first receiving antipsychotic drugs experience substantial deposition of both subcutaneous and intra-abdominal fat, reflecting a loss of the normal inhibitory control of leptin on body mass. Along with fat deposition, the increase in levels of fasting lipids and in non-fasting glucose may provide early signs of drug-induced progression towards the metabolic syndrome.
SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—X. A SPIN‐TRAPPING AND DIRECT ELECTRON SPIN RESONANCE STUDY OF THE PHOTOCHEMICAL PATHWAYS OF DAUNOMYCIN AND ADRIAMYCIN (1987)

Abstract— Irradiation of daunomycin (or adriamycin) and the spin trap 5,5‐dimethyl‐l‐pyrroline‐1‐oxide (DMPO) at 490 nm in the presence or in the absence of air generated the hydroxyl radical adduct (DMPO‐OH). The observed DMPO‐OH signal was not affected by the addition of hydroxyl radical scavengers (ethanol, formate), suggesting that direct trapping of the hydroxyl radical was not involved. The DMPO‐OH signal was insensitive to superoxide dismutase and catalase, which ruled out the possibility of superoxide or H 2 O 2 involvement. These findings demonstrate that daunomycin (or adriamycin) does not generate hydroxyl radicals or superoxide radical anions when subjected to 490‐nm excitation. However, when daunomycin (or adriamycin) was irradiated at 310 nm DMPO adducts derived from two carbon‐centered radicals, superoxide and the hydroxyl radical were detected. The superoxide adduct of DMPO was abolished by the addition of SOD, providing unequivocal evidence for the generation of the superoxide anion radical. The daunomycin semiquinone radical, observed upon 310‐nm irradiation of daunomycin in the absence of DMPO, appears to be the precursor of the superoxide radical anion. One of the carbon‐centered radicals trapped by DMPO exhibited a unique set of hyperfine parameters and was identified as an acyl radical. This suggests that the known photochemical deacylation of daunomycin occurs via a homolytic cleavage mechanism. The free radicals generated photolytically from adriamycin and daunomycin may be involved in the etiology of the skin ulceration and inflammation caused by these drugs. A knowledge of the dependence of these photogenerated radicals on the wavelength of excitation may be important in the development of adriamycin and daunomycin for photodynamic therapy.
Preparation, Physical Properties, On-Bead Binding Assay and Spectroscopic Reliability of 25 Barcoded Polystyrene−Poly(ethylene glycol) Graft Copolymers (2003)

Here we describe the preparation of 25 beaded polystyrene-poly(ethylene glycol) graft copolymers from six spectroscopically active styrene monomers: styrene, 2,5-dimethylstyrene, 4-methylstyrene, 2,4-dimethylstyrene, 4-tert-butylstyrene, and 3-methylstyrene. These polymers were thoroughly characterized by Raman, infrared, and (1)H/(13)C NMR spectroscopies, and differential scanning calorimetry. Determination of the swelling properties, peptide synthesis, and on-bead streptavidin-alkaline phosphatase (SAP) binding assay further established that their physical and chemical properties where not significantly altered by the diversity of their encoded polystyrene core. Each of the 25 resins displayed a unique Raman and infrared vibrational fingerprint, which was converted into a "spectroscopic barcode". The position of each bar matches the peak wavenumber in the corresponding spectrum but is independent of its intensity. From this simplified representation similarity maps comparing 35 000 resin pairs were generated to establish the spectroscopic barcoding as a reliable encoding methodology. In effect, in 99% of the cases, the highest similarity coefficients were obtained for resin pairs prepared from the same styrene derivatives even after SAP binding assay. We have also shown that a small but unique combination of a resin's vibrations (30-40%) is sufficient for its identification. However, in rare cases where a resin's vibrational signature has been severely compromised, both the Raman and infrared barcodes were synergistically and reliably utilized to unequivocally identify its chemical make up.
Design of a Serum Stability Tag for Bioactive Peptides (2013)

Serum has a high intrinsic proteolytic activity that leads to continuous processing of peptides and proteins. Strategies to protect bioactive peptides from serum proteolytic degradation include incorporation of unnatural amino acids, conformational constraints, large polymeric tags, or other synthetic manipulations such as amide bond replacements. Here we explored a possibility of designing a serum stability tag made of natural amino acids. We observed that a diproline motif (-Pro-Pro-) shows remarkable stability against serum endopeptidases. Accordingly, we designed close to 50 peptides to identify natural amino acids flanking the -Pro-Pro- sequence that can enhance the serum stability of this motif. As a result, a tetrapeptide with the sequence Asp-Pro-Pro-Glu (DPPE) was identified that remains intact in human serum for more than 24 h. at 37°C.
Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation (1996)

We have used a functional assay to identify a putative T-box transcription factor (Xombi) that has the ability to induce sites of invagination in the ectoderm of Xenopus embryos that resemble the blastopore lip. Maternal Xombi transcript is first localized to the oocyte's vegetal cortex and cytoplasm, early sources of mesoderm and endoderm-inducing signals. Soon after zygotic transcription begins, there is a wave of Xombi expression, beginning in dorsal mesoderm and then extending to lateral and ventral mesoderm, that precedes and parallels blastopore lip formation at the border between the mesoderm and endoderm. Transcripts encoding brachyury, Xwnt8 and goosecoid colocalize with Xombi transcripts within the marginal zone; ectopic expression of Xombi induces expression of all three mesodermal genes. In ectodermal explants, Xombi expression is induced by the secreted mesoderm inducers activinA, activinB, Xnrl and eFGF, and by brachyury, another Xenopus T-box containing gene. The time course and location of Xombi expression, its biological activities and the partial dependence of Xombi expression and blastopore lip formation on fibroblast growth factor (FGF) signaling suggest that Xombi contributes to a traveling wave of morphogenesis and differentiation during Xenopus gastrulation.
Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo. (1993)

The ras oncogene product, Ras, is synthesized in vivo as a precursor protein that requires post-translational processing to become biologically active and to be capable of transforming mammalian cells. Farnesylation appears to be a critical modification of Ras, and thus inhibitors of the farnesyl-protein transferase (FPTase) that catalyzes this reaction may block ras-dependent tumorigenesis. Three structural classes of FPTase inhibitors were identified: (alpha-hydroxyfarnesyl)phosphonic acid, chaetomellic acids, and zaragozic acids. By comparison, these compounds were weaker inhibitors of geranylgeranyl-protein transferases. Each of these inhibitors was competitive with respect to farnesyl diphosphate in the FPTase reaction. All compounds were assayed for inhibition of Ras processing in Ha-ras-transformed NIH3T3 fibroblasts. Ras processing was inhibited by 1 microM (alpha-hydroxyfarnesyl)phosphonic acid. Neither chaetomellic acid nor zaragozic acid were active in this assay. These results are the first demonstration that a small organic chemical selected for inhibition of FPTase can inhibit Ras processing in vivo.
Rodent Models of Experimental Autoimmune Uveitis (2012)

The model of experimental autoimmune uveitis (EAU) in mice and in rats is described. EAU targets immunologically privileged retinal antigens and serves as a model of autoimmune uveitis in humans as well as a model for autoimmunity in a more general sense. EAU is a well-characterized, robust, and reproducible model that is easily followed and quantitated. It is inducible with synthetic peptides derived from retinal autoantigens in commonly available strains of rats and mice. The ability to induce EAU in various gene-manipulated, including HLA-transgenic, mouse strains makes the EAU model suitable for the study of basic mechanisms as well as in clinically relevant interventions.
Effect of Rosemary Spice Extractive on Growth of Microorganisms in Meats1 (1976)

A study was conducted to examine the possible bacteriostatic and bactericidal effect of rosemary spice extractive (RSE) on growth of selected microflora and total bacterial populations in mechanically deboned poultry meat (MDPM), turkey breast, and beef. Definite bactericidal effect by 0.1% RSE became evident when a pure culture of Staphylococcus aureus was tested in a bacteriological medium. Such an effect was not observed when Escherichia coli, Enterobacter aerogenes, Pseudomonas fluorescens, and Salmonella typhimurium were tested. When various types of meat were used as growth media, RSE showed a bactericidal effect on S. aureus only at 5% concentration. Such an effect was not observed on total plate counts of the meat samples.
Women on the boards of Britain′s top 200 companies (1995)

Summarizes the findings of a 1993 report by Ashridge Management Group on women on the boards of the top 200 companies in Britain. Compares the results with a similar survey done in 1989. Finds that, although the number of women directors has doubled since 1989, they still represent only 4 per cent of all directorship appointments in the 200 companies surveyed, despite more women being recruited. More women are becoming non‐executive directors but the old‐boy network is still very much in operation. Discusses the issues which seem to account for the slow progress in women′s career ladders. Suggests an action list to enable companies to offer opportunities to women to gain skills and experience necessary to become directors.
16S rRNA Gene Sequencing for Bacterial Identification in the Diagnostic Laboratory: Pluses, Perils, and Pitfalls (2007)

The use of 16S rRNA gene sequences to study bacterial phylogeny and taxonomy has been by far the most common housekeeping genetic marker used for a number of reasons. These reasons include (i) its presence in almost all bacteria, often existing as a multigene family, or operons; (ii) the function of
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of BI 1356, an Inhibitor of Dipeptidyl Peptidase 4, in Healthy Male Volunteers (2008)

This randomized, double-blind, parallel, placebo-controlled, single rising-dose study investigated the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of BI 1356 (once-daily, given orally) in healthy men. BI 1356 was well tolerated and safe up to and including a dose of 600 mg. The incidence of drug-related adverse events was equal in subjects receiving BI 1356 (30%) or placebo (31%). No clinically relevant deviations in laboratory or ECG parameters were reported. Exposure of BI 1356 increased less than proportionally from 2.5 mg to 5 mg, more than proportionally from 25 mg to 100 mg and approximately proportionally for doses from 100 mg to 600 mg. The geometric mean terminal half-life was up to 184 hours. Renal excretion was low. All doses of BI 1356 inhibited plasma dipeptidyl peptidase 4 activity. Single doses of 2.5 mg and 5 mg inhibited dipeptidyl peptidase 4 activity by 72.7% and 86.1% from baseline, respectively. The time to achieve maximum inhibition shifted with increasing doses from 3 hours (2.5 mg) to <0.7 hours (> or =200 mg). Within the dose range tested, a direct pharmacokinetic/pharmacodynamic relationship was observed. The pharmacokinetic and pharmacodynamic profile results demonstrate the potency and full 24-hour duration of action of BI 1356. Based on an estimated therapeutic dose of 5 mg, the therapeutic window of BI 1356 is expected to be >100-fold.
Microbial Production of Hydrogen: An Overview (1998)

Production of hydrogen by anaerobes, facultative anaerobes, aerobes, methylotrophs, and photosynthetic bacteria is possible. Anaerobic Clostridia are potential producers and immobilized C. butyricum produces 2 mol H2/mol glucose at 50% efficiency. Spontaneous production of H2 from formate and glucose by immobilized Escherichia coli showed 100% and 60% efficiencies, respectively. Enterobactericiae produces H2 at similar efficiency from different monosaccharides during growth. Among methylotrophs, methanogenes, rumen bacteria, and thermophilic archae, Ruminococcus albus, is promising (2.37 mol/mol glucose). Immobilized aerobic Bacillus licheniformis optimally produces 0.7 mol H2/mol glucose. Photosynthetic Rhodospirillum rubrum produces 4, 7, and 6 mol of H2 from acetate, succinate, and malate, respectively. Excellent productivity (6.2 mol H2/mol glucose) by co-cultures of Cellulomonas with a hydrogenase uptake (Hup) mutant of R. capsulata on cellulose was found. Cyanobacteria, viz., Anabaena, Synechococcus, and Oscillatoria sp., have been studied for photoproduction of H2. Immobilized A. cylindrica produces H2 (20 ml/g dry wt/h) continually for 1 year. Increased H2 productivity was found for Hup mutant of A. variabilis. Synechococcus sp. has a high potential for H2 production in fermentors and outdoor cultures. Simultaneous productions of oxychemicals and H2 by Klebseilla sp. and by enzymatic methods were also attempted. The fate of H2 biotechnology is presumed to be dictated by the stock of fossil fuel and state of pollution in future.