gebhart/patrepeval huggingface dataset:
UTP inhibits Na+ absorption in wild-type and ΔF508 CFTR-expressing human bronchial epithelia (1999)

Ca2+-mediated agonists, including UTP, are being developed for therapeutic use in cystic fibrosis (CF) based on their ability to modulate alternative Cl- conductances. As CF is also characterized by hyperabsorption of Na+, we determined the effect of mucosal UTP on transepithelial Na+ transport in primary cultures of human bronchial epithelia (HBE). In symmetrical NaCl, UTP induced an initial increase in short-circuit current (Isc) followed by a sustained inhibition. To differentiate between effects on Na+ absorption and Cl- secretion, Isc was measured in the absence of mucosal and serosal Cl- (INa). Again, mucosal UTP induced an initial increase and then a sustained decrease that reduced amiloride-sensitive INa by 73%. The Ca2+-dependent agonists histamine, bradykinin, serosal UTP, and thapsigargin similarly induced sustained inhibition (62-84%) of INa. Mucosal UTP induced similar sustained inhibition (half-maximal inhibitory concentration 296 nM) of INa in primary cultures of human CF airway homozygous for the DeltaF508 mutation. BAPTA-AM blunted UTP-dependent inhibition of INa, but inhibitors of protein kinase C (PKC) and phospholipase A2 had no effect. Indeed, direct activation of PKC by phorbol 12-myristate 13-acetate failed to inhibit Na+ absorption. Apyrase, a tri- and diphosphatase, did not reverse inhibitory effects of UTP on INa, suggesting a long-term inhibitory effect of UTP that is independent of receptor occupancy. After establishment of a mucosa-to-serosa K+ concentration gradient and permeabilization of the mucosal membrane with nystatin, mucosal UTP induced an initial increase in K+ current followed by a sustained inhibition. We conclude that increasing cellular Ca2+ induces a long-term inhibition of transepithelial Na+ transport across normal and CF HBE at least partly due to downregulation of a basolateral membrane K+ conductance. Thus UTP may have a dual therapeutic effect in CF airway: 1) stimulation of a Cl- secretory response and 2) inhibition of Na+ transport.
The Effect of Altering Skin-Surface Cooling Speeds on Vasoconstriction and Shivering Thresholds (2011)

Onset of vasoconstriction and shivering occurred at similar mean skin temperatures with all 3 cooling rates. Aggressive surface cooling can thus be used in thermoregulatory studies and for induction of therapeutic hypothermia without provoking dynamic thermoregulatory defenses.
Current noise reveals protonation kinetics and number of ionizable sites in an open protein ion channel (1993)

In analogy to current fluctuations found in solid state electronic microstructure devices, excess noise generated by the reversible ionization of sites in a transmembrane ionic channel was observed. By analyzing the pH-dependent fluctuations in the current through fully open single channels formed by the \ensuremath{\alpha}-toxin protein, we were able to evaluate the protonation rate constants, the number of sites participating in the protonation process, and the effect of recharging a single site on the channel conductance.
Down-Regulation of Estrogen Receptors by Androgens in the ZR-75-1 Human Breast Cancer Cell Line* (1989)

Much clinical evidence indicates that androgens have beneficial effects in the treatment of breast cancer in women. Physiological concentrations of androgens strongly inhibit both basal and estrogen-induced cell proliferation in the human breast cancer cell line ZR-75-1 through their interaction with the androgen receptor. The present study shows that androgens strongly suppress estrogen receptor (ER) and progesterone receptor contents in this model, as measured by radioligand binding and anti-ER monoclonal antibodies. Similar inhibitory effects are observed on the levels of ER messenger RNA (mRNA) measured by ribonuclease protection assay. The androgenic effect is observed at subnanomolar concentrations of the nonaromatizable androgen 5 alpha-dihydrotestosterone, regardless of the presence of estrogens, and is competitively reversed by the antiandrogen hydroxyflutamide. Such data on ER expression provide an explanation for at least part of the antiestrogenic effects of androgens on breast cancer cell growth and moreover suggest that the specific inhibitory effects of androgen therapy could be additive to the standard treatment limited to blockade of estrogens by antiestrogens.
Mechanistic Studies of the Ethylene Trimerization Reaction with Chromium−Diphosphine Catalysts:  Experimental Evidence for a Mechanism Involving Metallacyclic Intermediates (2004)

A system for catalytic trimerization of ethylene utilizing CrCl3(THF)3 and a diphosphine ligand PNPOMe [= (o-MeO-C6H4)2PN(Me)P(o-MeO-C6H4)2] has been investigated. The coordination chemistry of chromium with PNPOMe has been explored, and (PNPOMe)CrCl3 and (PNPOMe)CrPh3 (3) have been synthesized by ether displacement from chromium(III) precursors. Salt metathesis of (PNPOMe)CrCl3 with o,o'-biphenyldiyl Grignard affords (PNPOMe)Cr(o,o'-biphenyldiyl)Br (4). Activation of 3 with H(Et2O)2B[C6H3(CF3)2]4 or 4 with NaB[C6H3(CF3)2]4 generates a catalytic system and trimerizes a 1:1 mixture of C2D4 and C2H4 to give isotopomers of 1-hexene without H/D scrambling (C6D12, C6D8H4, C6D4H8, and C6H12 in a 1:3:3:1 ratio). The lack of crossover supports a mechanism involving metallacyclic intermediates. The mechanism of the ethylene trimerization reaction has also been studied by the reaction of trans-, cis-, and gem-ethylene-d2 with 4 upon activation with NaB[C6H3(CF3)2]4.
Broadband ISDN and asynchronous transfer mode (ATM) (1989)

The transfer mode chosen by the CCITT Study Group XVIII Task Group on ISDN Broadband Aspects as the basis of broadband ISDN is called the asynchronous transfer mode (ATM). ATM is a high-bandwidth, low-delay, packetlike switching and multiplexing technique. It is essentially a connection-oriented technique, although it is envisioned as a basis for supporting all services, connectionless as well as connection-oriented. The basic transfer mode concepts are explained. The limits of synchronous transfer mode (ATM) are discussed and reasons for choosing ATM over STM are given. The main technical issues having an impact on the ATM specifications are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
On-chip silicon odometers and their potential use in medical electronics (2012)

The parametric shifts or circuit failures caused by transistor aging have become more severe with shrinking device sizes and voltage margins. Designing circuits that can withstand these aging effects is particularly critical in medical applications where systems must operate flawlessly across a range of conditions for their entire lifetimes. In this work we present several on-chip Silicon Odometers that provide measurement data required to develop transistor degradation models. One such scheme-a beat frequency detection circuit capable of recording oscillator frequency shifts ranging down to a theoretical limit of less than 0.01%-may be suited to trigger real-time adjustments that compensate for lost performance on products in the field. Incorporating this sensing capability may be especially attractive in implantable medical electronics.
HAMAP in 2015: updates to the protein family classification and annotation system (2014)

HAMAP (High-quality Automated and Manual Annotation of Proteins--available at http://hamap.expasy.org/) is a system for the automatic classification and annotation of protein sequences. HAMAP provides annotation of the same quality and detail as UniProtKB/Swiss-Prot, using manually curated profiles for protein sequence family classification and expert curated rules for functional annotation of family members. HAMAP data and tools are made available through our website and as part of the UniRule pipeline of UniProt, providing annotation for millions of unreviewed sequences of UniProtKB/TrEMBL. Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013. We continue to augment HAMAP with new family profiles and annotation rules as new protein families are characterized and annotated in UniProtKB/Swiss-Prot; the latest version of HAMAP (as of 3 September 2014) contains 1983 family classification profiles and 1998 annotation rules (up from 1780 and 1720). We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families. We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorithm.
Perspectives in Chagas Disease Treatment (2015)

Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. (1996)

The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin decreases food intake. Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection. Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters. In fasted adipose tissue to levels similar to fed control animals. There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake. TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin in mRNA in adipose tissue. As assessed by immuknoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA. Induction of leptin during the host response to infection may contribute to the anorexia of infection.
Selenite Reduction by the Thioredoxin System: Kinetics and Identification of Protein-Bound Selenide (2011)

Selenite (SeO(3)(2-)) assimilation into a bacterial selenoprotein depends on thioredoxin (trx) reductase in Esherichia coli, but the molecular mechanism has not been elucidated. The mineral-oil overlay method made it possible to carry out anaerobic enzyme assay, which demonstrated an initial lag-phase followed by time-dependent steady NADPH consumption with a positive cooperativity toward selenite and trx. SDS-PAGE/autoradiography using (75)Se-labeled selenite as substrate revealed the formation of trx-bound selenium in the reaction mixture. The protein-bound selenium has metabolic significance in being stabilized in the divalent state, and it also produced the selenopersulfide (-S-SeH) form by the catalysis of E. coli trx reductase (TrxB).
HORMONAL REGULATION OF HEPATIC GLUCONEOGENESIS AND GLYCOLYSIS (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis (1991)

The expression of many of the known virulence determinants of Bordetella pertussis is coordinately regulated by the vir regulatory locus and reduced in response to environmental signals called modulators. We have previously identified eight TnphoA gene fusions in B. pertussis in which the expression of alkaline phosphatase was maximal in the absence of the modulators nicotinic acid and MgSO4. We have termed the genes identified by these fusions vir-activated genes. Here we report the characterization of these TnphoA mutant strains. Four fusion strains were defective in known virulence determinants. For one of these, fusion strain SK39, Southern blot hybridization demonstrated that TnphoA was inserted in the S1 subunit gene of pertussis toxin. Hemagglutination assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblots identified three fusions strains, SK16, SK75, and SK91, that were defective in filamentous hemagglutinin. Whereas all three filamentous hemagglutinin-defective mutants showed either normal or enhanced colonization, the pertussis toxin-defective mutant showed a marked defect in pulmonary persistence. Of the four other fusion strains, two were deficient in outer membrane proteins. One of these, strain SK8, was defective in a major outer membrane protein of 95 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This strain colonized mouse lungs less well and did not induce lymphocytosis after aerosol challenge. The other strain, SK34, was defective in four outer membrane proteins, three of which were detectable only on a Western blot with polyclonal sera against B. pertussis. Two of our gene fusion strains did not show any defect in identifiable vir-regulated proteins.
Structure and molecular model refinement of Aspergillus oryzae (TAKA) α-amylase: an application of the simulated-annealing method (1991)

Monoclinic crystals of a neutral alpha-amylase from Aspergillus oryzae, containing three molecules in the asymmetric unit, have been reported previously and studied at 3 A resolution [Matsuura, Kunusoki, Harada & Kakudo (1984). J. Biochem. 95, 697-702]. Here we report the solution of the structure of this enzyme in a different crystal form (space group P2(1)2(1)2(1), a = 50.9, b = 67.2, c = 132.7 A), with only one molecule in the asymmetric unit. The structure was solved by the molecular replacement method, using a model of acid alpha-amylase from a related fungus A. niger [Brady, Brzozowski, Derewenda, Dodson & Dodson (1991). Acta Cryst. B47, 527-535]. Conventional least-squares crystallographic refinement failed to converge in a satisfactory manner, and the technique of molecular dynamics in the form of the XPLOR package [Brunger (1988). XPLOR Manual. Yale Univ., USA] was used to overcome the problem. A large rigid-body type movement of the C-terminal domain was identified and accounted for. The final round of restrained least-squares refinement (at 2.1 A resolution) including 3675 protein atoms and 247 water molecules resulted in a conventional crystallographic R factor of 0.183 and an atomic model which conforms well to standard stereochemical parameters (standard deviation of bond lengths from their expected values is 0.028 A, while that for planar groups is 0.029 A).
Neurovirulence and Immunogenicity of Attenuated Recombinant Vesicular Stomatitis Viruses in Nonhuman Primates (2014)

The work described in this article demonstrates a rational approach to the attenuation of vesicular stomatitis virus neurovirulence. The major attenuation strategy described here will be most likely applicable to other members of the Rhabdoviridae and possibly other families of nonsegmented negative-strand RNA viruses. These studies have also enabled the identification of an attenuated, replication-competent rVSIV vector that has successfully undergone its first clinical evaluation in humans. Therefore, these studies represent a major milestone in the development of attenuated rVSIV, and likely other vesiculoviruses, as a new vaccine platform(s) for use in humans.
Influence of Calcium Ion on the Binding of Fibrin Amino Terminal Peptides to Fibrinogen (1981)

The affinity of the amino terminal tetrapeptide of the beta chain of fibrin, Gly-His-Arg-Pro, for fibrinogen dramatically increases in the presence of 2 millimolar calcium ion. In contrast, there is no significant increase in the affinity of peptides beginning with the amino terminal sequence of the fibrin alpha chain, Gly-Pro-Arg, in the presence of calcium ions, although the number of binding sites increases. In the latter case, the increased number of sites is due to the alpha chain analogs binding to the site ordinarily occupied by the beta chain analogs. These results indicate that structures at the amino terminus of the fibrin beta chain play a more important role in fibrin polymerization when calcium ions are present.
Response characteristics of cutaneous cold receptors in the monkey (1977)

1. The receptive fields of 48 specific cold units, located in the hairy and glaborous skin of fore- and hindlimbs of rhesus monkeys, were mapped and scale drawings made. Forty-five percent had single spotlike receptive fields of 1-2 mm diameter or were up to 2 mm wide and 3-5 mm long, and formed straight, crescent, or right-angle shapes. The remaining 55% had two to five discrete spots or small areas innervated by a single fiber. Area or number of receptive fields per unit did not vary significantly along the limb axis. 2. Of the 48 specific cold units, 15 were held sufficiently long to record their dynamic responses to intensity-rate series of temperature changes from several adapting temperatures (ATs) between 20 and 45 degrees C. Six cold units showed a paradoxical increase in the steady-state response at the 45 degrees C compared to that at the 40 degrees C AT. Of the 15 cold units, 7 discharged in bursts at the 35 degrees C or lower ATs. The proportion of short intervals (intraburst intervals) increased as the adapting temperature decreased. 3. Both the latency and the temperature change at the onset of the dynamic response to cooling remained relatively constant for ATs up to and including 35 degrees C. The response latencies were approximately 200-400 ms, while the temperature changes at response onset were -0.02 to -0.06 degrees C. Both increased sharply at the 40 degrees C and still more at the 45 degrees C ATs. 4. The rate of increase in the frequency of the dynamic response to cooling by the fast rate increased to maximum at the 30 degrees C AT and then decreased at the higher ATs. For the slow rate the highest rate of increase in frequency occurred at the 20 degrees C AT. The fast rate of cooling always induced a faster rate of increase in frequency than slow rate of cooling. 5. Four indices of response magnitude were used in the analysis of the dynamic responses. These were peak frequency, cumulative impulses in the first 4 s following stimulus onset, average frequency during stimulations plus 3 s, and the total impulses during stimulation. The first three indices gave similar representations of the dynamic responses to the rate and intensity of cooling and the effect of the AT. The slow rate of cooling invariably yielded a smaller index of response magnitude than the fast rate. The difference became more pronounced as the intensity of cooling increased. The stimulus intensity-response magnitude functions were nonlinear. This nonlinearity was more pronounced at the low than at the high ATs. As the AT was increased, the response indices approached linearity at the 35 and 40 degrees C ATs. The greatest sensitivity of cold units to cooling was from the 35 degrees C AT. The fourth index, total impulses during stimulation minus steady state, gave a different picture. This index of response magnitude was linearly related to stimulus intensity for both rates of cooling from all adapting temperatures except for the slow rate of cooling from the 45 degrees C AT...
Gene transfer in humans using a conditionally replicating lentiviral vector (2006)

We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.
Developing an Injectable Formula Containing an Oxygen-Sensitive Drug: A Case Study of Danofloxacin Injectable (1999)

The purpose of this study was to assess the impact of impurities in formulation components, antioxidants, formulation pH, and processing/packaging on the extent of color change associated with oxidation of danofloxacin injectable. The methods used in this study include reversed-phase HPLC, UV-VIS spectrophotometry, atomic absorption spectroscopy, visual observation, and iodimetric titration for quantification of the antioxidant. The results from this study revealed that trace impurities from two different excipients significantly contributed to color change associated with oxidation. Polyvinyl pyrrolidone (PVP) introduced trace levels of peroxides into the solution. A second excipient also had a significant impact on stability because it introduced trace metal impurities into the product. The minimization of oxygen levels alone in the solution and headspace was not sufficient to completely eliminate the product instability. The addition of an antioxidant, monothioglycerol (MTG), resulted in a formulation less sensitive to processing variables. The impact of pH on the performance of MTG was also studied. At pH 7.5, MTG resulted in significant improvement in stability; however, at pH 6.0 it was not effective as an antioxidant. Process modifications alone may not be sufficient to prevent oxidation. Chemical approaches, such as pH control, addition of an antioxidant, and control of components should be considered first as means of enhancing stability of oxygen-sensitive solutions.
Glass-forming range in mechanically alloyed Ni-Zr and the influence of the milling intensity (1988)

Amorphous Ni-Zr powders have been prepared by mechanical alloying from crystalline elemental powders. The glass-forming range has been determined by x-ray diffraction, differential scanning calorimetry and saturation magnetization measurements. From 27 to 83 at. % Ni the powders become amorphous. This shows that deep eutectics do not play any role, contrary to amorphization by melt spinning. Crystallization temperatures, crystallization enthalpies, and wave numbers Qp, obtained from x-ray diffraction investigations, are compared with the data received for rapidly quenched samples. In addition, the effect of the milling intensity on the glass formation has been studied for the first time. If the intensity is too high, crystalline intermetallic phases are formed. On the other hand, the powder needs an extended milling time to become completely amorphous if the milling intensity is too low. Conclusions on the actual temperature of the individual particle during mechanical alloying and on the glass-forming process are drawn from these results.