gebhart/patrepeval huggingface dataset:
Chronic systemic administration of salmeterol to rats promotes pulmonary β2‐adrenoceptor desensitization and down‐regulation of Gsα (2001)

1. The aim of the present study was to examine the effects of chronic infusion of the long-acting agonist salmeterol on pulmonary beta(2)-adrenoceptor function in Sprague-Dawley rats in vivo and to elucidate the molecular basis of any altered state. 2. Systemic administration of rats with salmeterol for 7 days compromised the ability of salmeterol and prostaglandin E(2) (PGE(2)), given acutely by the intravenous route, to protect against ACh-induced bronchoconstriction when compared to rats treated identically with vehicle. 3. beta(1)- and beta(2)-adrenoceptor density was significantly reduced in lung membranes harvested from salmeterol-treated animals, which was associated with impaired salmeterol- and PGE(2)-induced cyclic AMP accumulation ex vivo. 4. Three variants of G(s alpha) that migrated as 42, 44 and 52 kDa peptides on SDS polyacrylamide gels were detected in lung membranes prepared from both groups of rats but the intensity of each isoform was markedly reduced in rats that received salmeterol. 5. The activity of cytosolic, but not membrane-associated, G-protein receptor-coupled kinase was elevated in the lung of salmeterol-treated rats when compared to vehicle-treated animals. 6. The ability of salmeterol, administered systemically, to protect the airways of untreated rats against ACh-induced bronchoconstriction was short-acting (t(off) approximately 45 min), which contrasts with its long-acting nature when given to asthmatic subjects by inhalation. 7. These results indicate that chronic treatment of rats with salmeterol results in heterologous desensitization of pulmonary G(s)-coupled receptors. In light of previous data obtained in rats treated chronically with salbutamol, we propose that a primary mechanism responsible for this effect is a reduction in membrane-associated G(s alpha). The short-acting nature of salmeterol, when administered systemically, and the reduction in beta-adrenoceptor number may be due to metabolism to a biologically-active, short-acting and non-selective beta-adrenoceptor agonist.
Hartmann Sensing At Adaptive Optics Associates (1987)

A review of the current practice in wavefront sensor design at Adaptive Optics Associates (AOA) is presented. The principles of Hartmann sensing and matrix reconstruction are reviewed, and sensor performance required for compensation of atmospheric imaging is estimated. The structure of the digital processor based sensors built at AOA is discussed, with two recent systems as examples.
Adaptive homogeneity-directed demosaicing algorithm (2005)

A cost-effective digital camera uses a single-image sensor, applying alternating patterns of red, green, and blue color filters to each pixel location. A way to reconstruct a full three-color representation of color images by estimating the missing pixel components in each color plane is called a demosaicing algorithm. This paper presents three inherent problems often associated with demosaicing algorithms that incorporate two-dimensional (2-D) directional interpolation: misguidance color artifacts, interpolation color artifacts, and aliasing. The level of misguidance color artifacts present in two images can be compared using metric neighborhood modeling. The proposed demosaicing algorithm estimates missing pixels by interpolating in the direction with fewer color artifacts. The aliasing problem is addressed by applying filterbank techniques to 2-D directional interpolation. The interpolation artifacts are reduced using a nonlinear iterative procedure. Experimental results using digital images confirm the effectiveness of this approach.
Overexpression and characterization of a prolyl endopeptidase from the hyperthermophilic archaeon Pyrococcus furiosus (1997)

The maltose-regulated mlr-2 gene from the hyperthermophilic archaeon Pyrococcus furiosus having homology to bacterial and eukaryal prolyl endopeptidase (PEPase) was cloned and overexpressed in Escherichia coli. Extracts from recombinant cells were capable of hydrolyzing the PEPase substrate benzyloxycarbonyl-Gly-Pro-p-nitroanilide (ZGPpNA) with a temperature optimum between 85 and 90 degrees C. Denaturing gel electrophoresis of purified PEPase showed that enzyme activity was associated with a 70-kDa protein, which is consistent with that predicted from the mlr-2 sequence. However, an apparent molecular mass of 59 kDa was obtained from gel permeation studies. In addition to ZGPpNA (K(Mapp) of 53 microM), PEPase was capable of hydrolyzing azocasein, although at a low rate. No activity was detected when ZGPpNA was replaced by substrates for carboxypeptidase A and B, chymotrypsin, subtilisin, and neutral endopeptidase. N-[N-(L-3-trans-Carboxirane-2-carbonyl)-L-Leu]-agmatine (E-64) and tosyl-L-Lys chloromethyl ketone did not inhibit PEPase activity. Both phenylmethylsulfonyl fluoride and diprotin A inhibited ZGPpNA cleavage, the latter doing so competitively (K(lapp) of 343 microM). At 100 degrees C, the enzyme displayed some tolerance to sodium dodecyl sulfate treatment. Stability of PEPase over time was dependent on protein concentration; at temperatures above 65 degrees C, dilute samples retained most of their activity after 24 h while the activity of concentrated preparations diminished significantly. This decrease was found to be due, in part, to autoproteolysis. Partially purified PEPase from P. furiosus exhibited the same temperature optimum, molecular weight, and kinetic characteristics as the enzyme overexpressed in E. coli. Extracts from P. furiosus cultures grown in the presence of maltose were approximately sevenfold greater in PEPase activity than those grown without maltose. Activity could not be detected in clarified medium obtained from maltose-grown cultures. We conclude that mlr-2, now called prpA, encodes PEPase; the physiological role of this protease is presently unknown.
Stochastic neural computation. I. Computational elements (2001)

This paper examines a number of stochastic computational elements employed in artificial neural networks, several of which are introduced for the first time, together with an analysis of their operation. We briefly include multiplication, squaring, addition, subtraction, and division circuits in both unipolar and bipolar formats, the principles of which are well-known, at least for unipolar signals. We have introduced several modifications to improve the speed of the division operation. The primary contribution of this paper, however, is in introducing several state machine-based computational elements for performing sigmoid nonlinearity mappings, linear gain, and exponentiation functions. We also describe an efficient method for the generation of, and conversion between, stochastic and deterministic binary signals. The validity of the present approach is demonstrated in a companion paper through a sample application, the recognition of noisy optical characters using soft competitive learning. Network generalization capabilities of the stochastic network maintain a squared error within 10 percent of that of a floating-point implementation for a wide range of noise levels. While the accuracy of stochastic computation may not compare favorably with more conventional binary radix-based computation, the low circuit area, power, and speed characteristics may, in certain situations, make them attractive for VLSI implementation of artificial neural networks.
High-Dimensional ODEs Coupled With Mixed-Effects Modeling Techniques for Dynamic Gene Regulatory Network Identification (2011)

Gene regulation is a complicated process. The interaction of many genes and their products forms an intricate biological network. Identification of this dynamic network will help us understand the biological process in a systematic way. However, the construction of such a dynamic network is very challenging for a high-dimensional system. In this article we propose to use a set of ordinary differential equations (ODE), coupled with dimensional reduction by clustering and mixed-effects modeling techniques, to model the dynamic gene regulatory network (GRN). The ODE models allow us to quantify both positive and negative gene regulations as well as feedback effects of one set of genes in a functional module on the dynamic expression changes of the genes in another functional module, which results in a directed graph network. A five-step procedure, Clustering, Smoothing, regulation Identification, parameter Estimates refining and Function enrichment analysis (CSIEF) is developed to identify the ODE-based dynamic GRN. In the proposed CSIEF procedure, a series of cutting-edge statistical methods and techniques are employed, that include non-parametric mixed-effects models with a mixture distribution for clustering, nonparametric mixed-effects smoothing-based methods for ODE models, the smoothly clipped absolute deviation (SCAD)-based variable selection, and stochastic approximation EM (SAEM) approach for mixed-effects ODE model parameter estimation. The key step, the SCAD-based variable selection of the proposed procedure is justified by investigating its asymptotic properties and validated by Monte Carlo simulations. We apply the proposed method to identify the dynamic GRN for yeast cell cycle progression data. We are able to annotate the identified modules through function enrichment analyses. Some interesting biological findings are discussed. The proposed procedure is a promising tool for constructing a general dynamic GRN and more complicated dynamic networks.
Interleukin-31 promotes pathogenic mechanisms underlying skin and lung fibrosis in scleroderma (2020)

IL-31/IL-31RA is confirmed as a candidate pro-fibrotic pathway, which may contribute to skin and lung fibrosis in a subset of scleroderma patients.
From Reservoir Through Process, From Today to Tomorrow—The Integrated Asset Model (2006)

Abstract Simulation technology from reservoir through process facility has advanced so much, that field development strategies can be developed within a new systematic workflow, using existing applications from many E&amp;P departments. Detailed production data from many sources can be used within simulation models to give a good representation of future field wide behavior. In this paper a fictional case study of a reservoir that has been producing for some 12 years will be examined. The wells are all producing into a sub-sea manifold and then tied back via a 60km flow line and riser system. The reservoir is in severe decline with field production well below the original design capacity of the production system and surface facilities. Hence, further development options are being investigated for this asset. A new, nearby, reservoir has been discovered. A reservoir simulation model has been constructed for the new discovery. This second reservoir is a gas condensate system, much smaller than the existing reservoir and located 90 kms to the east. The current development plan shows six wells drilled and brought into production over an 18 month period. Reservoir 2 is a marginal development, the viability of producing this reservoir will depend on quantification of the reservoir uncertainty and finding a cost effective development strategy with existing processing facilities. The Business Development Team has suggested a number of possible options for developing this new reservoir; Option 1 involves tying in the new reservoir to the existing sub-sea infrastructure. Option 2 is to install a complete new flow line from the sub-sea template of the new reservoir and run this directly to the existing platform. But how do these options effect reservoir management and surface facilities performance? Evaluation is achieved by constructing an integrated asset model of the entire field, allowing the reservoir through facilities interaction to be evaluated in detail.
Anti-tumour necrosis factor (TNF)-alpha therapy in undifferentiated spondyloarthropathy. (2003)

The cytokine tumour necrosis factor (TNF)-alpha plays a major role in the spinal inflammatory process of spondyloarthropathy. In contrast to rheumatoid arthritis, disease modifying antirheumatic drugs have not been proved effective against inflammation and progressive ankylosis. Initial studies on TNFalpha inhibitors in ankylosing spondylitis are promising and raise the question as to whether early stages of the disease, mostly classified as "undifferentiated spondyloarthropathy" (uSpA), should also be treated with TNFalpha inhibitors. This article summarises the preliminary results of 11 uSpA patients in 4 different trials treated with TNFalpha inhibitors.
Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix (2007)

The conjunctive presence of mechanical stress and active transforming growth factor beta1 (TGF-beta1) is essential to convert fibroblasts into contractile myofibroblasts, which cause tissue contractures in fibrotic diseases. Using cultured myofibroblasts and conditions that permit tension modulation on the extracellular matrix (ECM), we establish that myofibroblast contraction functions as a mechanism to directly activate TGF-beta1 from self-generated stores in the ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with Triton X-100 releases active TGF-beta1 from the ECM. This process is inhibited either by antagonizing integrins or reducing ECM compliance and is independent from protease activity. Stretching myofibroblast-derived ECM in the presence of mechanically apposing stress fibers immediately activates latent TGF-beta1. In myofibroblast-populated wounds, activation of the downstream targets of TGF-beta1 signaling Smad2/3 is higher in stressed compared to relaxed tissues despite similar levels of total TGF-beta1 and its receptor. We propose activation of TGF-beta1 via integrin-mediated myofibroblast contraction as a potential checkpoint in the progression of fibrosis, restricting autocrine generation of myofibroblasts to a stiffened ECM.
Application of environmental scanning electron microscopy to determine biological surface structure (2009)

The use of environmental scanning electron microscopy in biology is growing as more becomes understood about the advantages and limitations of the technique. These are discussed and we include new evidence about the effect of environmental scanning electron microscopy imaging on the viability of mammalian cells. We show that although specimen preparation for high-vacuum scanning electron microscopy introduces some artefacts, there are also challenges in the use of environmental scanning electron microscopy, particularly at higher resolutions. This suggests the two technologies are best used in combination. We have used human monocyte-derived macrophages as a test sample, imaging their complicated and delicate membrane ruffles and protrusions. We have also explored the possibility of using environmental scanning electron microscopy for dynamic experiments, finding that mammalian cells cannot be imaged and kept alive in the environmental scanning electron microscopy. The dehydration step in which the cell surface is exposed causes irreversible damage, probably via loss of membrane integrity during liquid removal in the specimen chamber. Therefore, mammalian cells should be imaged after fixation where possible to protect against damage as a result of chamber conditions.
Students' Perceived Usefulness and Relevance of Communication Skills in the Basic Course: Comparing University and Community College Students (2001)

Communication skills training is extremely important in terms of students’ career choices. However, few studies have been conducted regarding differences between community colleges and four-year universities in terms of students’ perceived usefulness and relevance of the study of communication in relation to career choice. The present study extends extant research by examining students’ perceptions of this issue. The participants in Study 1 were 155 community college and 291 four-year university students and the participants in Study 2 were 205 community college students.
A Prospective, Randomized Study: Switch Off the Sacral Nerve Stimulator During the Night? (2008)

It could be considered to recommend compliant patients to "switch off" the pacemaker during the night to extend the lifetime of the pacemaker. One-third experienced increased soiling, and they should turn the pacemaker on all day and night. Among the remaining, only a minor proportion will be motivated for turning the pacemaker off.
CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl–positive human leukemia cells to apoptosis due to antileukemic drugs (2000)

The differentiation and apoptosis-sensitizing effects of the Bcr-Abl-specific tyrosine kinase inhibitor CGP57148B, also known as STI-571, were determined in human Bcr-Abl-positive HL-60/Bcr-Abl and K562 cells. First, the results demonstrate that the ectopic expression of the p185 Bcr-Abl fusion protein induced hemoglobin in the acute myeloid leukemia (AML) HL-60 cells. Exposure to low-dose cytosine arabinoside (Ara-C; 10 nmol/L) increased hemoglobin levels in HL-60/Bcr-Abl and in the chronic myeloid leukemia (CML) blast crisis K562 cells, which express the p210 Bcr-Abl protein. As compared with HL-60/neo, HL-60/Bcr-Abl and K562 cells were resistant to apoptosis induced by Ara-C, doxorubicin, or tumor necrosis factor-alpha (TNF-alpha), which was associated with reduced processing of caspase-8 and Bid protein and decreased cytosolic accumulation of cytochrome c (cyt c). Exposure to CGP57148B alone increased hemoglobin levels and CD11b expression and induced apoptosis of HL-60/Bcr-Abl and K562 cells. CGP57148B treatment down-regulated antiapoptotic XIAP, cIAP1, and Bcl-x(L), without affecting Bcl-2, Bax, Apaf-1, Fas (CD95), Fas ligand, Abl, and Bcr-Abl levels. CGP57148B also inhibited constitutively active Akt kinase and NFkappaB in Bcr-Abl-positive cells. Attenuation of NFkappaB activity by ectopic expression of transdominant repressor of IkappaB sensitized HL-60/Bcr-Abl and K562 cells to TNF-alpha but not to apoptosis induced by Ara-C or doxorubicin. Importantly, cotreatment with CGP57148B significantly increased Ara-C- or doxorubicin-induced apoptosis of HL-60/Bcr-Abl and K562 cells. This was associated with greater cytosolic accumulation of cyt c and PARP cleavage activity of caspase-3. These in vitro data indicate that combinations of CGP57148B and antileukemic drugs such as Ara-C may have improved in vivo efficacy against Bcr-Abl-positive acute leukemia.
Synthesis of imidazo-fused bridgehead-nitrogen C-nucleosides via dehydrative coupling reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (1984)

A short, efficient synthesis of novel imidazo-fused bridgehead-nitrogen C-nucleosides has been developed. Dehydrative coupling of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (14) with a series of aminoalkyl-substituted heterocycles (6)–(8) gives the amides (15)–(17). The latter are subsequently converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-a]pyrazine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f]-1,2,4-triazine C-nucleosides (20) and (21). The synthesis of a novel adenosine isostere, 8-amino-3-β-D-ribofuranosylimidazo[1,5-a]pyrazine (32), is described.
Local vaccination with killed Streptococcus uberis protects the bovine mammary gland against experimental intramammary challenge with the homologous strain (1994)

The ability of killed streptococcus uberis to induce protection against mastitis when administered either into the cistern of the dry mammary gland (intramammary vaccination) without adjuvant or subcutaneously with adjuvant was investigated. Bacteria were never reisolated from vaccinated quarters following challenge with the same strain during the subsequent lactation, and no inflammatory response was detected. In contrast, following subcutaneous vaccination, milk from challenged quarters contained very small numbers of bacteria, but these quarters did exhibit clinical disease, whereas quarters on nonvaccinated control animals produced discolored, clotted secretion with large numbers of bacteria and somatic cells and required antibiotic therapy by 60 h postchallenge. There was a significant increase in the levels of S. uberis-specific immunoglobulin G1 (IgG1), IgG2, and IgM in milk following intramammary vaccination and in the levels of specific IgG1 and IgG2 in milk following subcutaneous vaccination. Levels of specific antibody in serum were also elevated following vaccination by either route. However, despite this, there was no increase in the opsonic activity of serum or milk. Both peripheral blood lymphocytes and dry-period mammary gland lymphocytes showed strong proliferative responses to S. uberis in vitro following subcutaneous vaccination, but only mammary gland lymphocytes responded following intramammary vaccination. It was concluded that the protection seen in vaccinated quarters did not appear to be related to levels of specific antibody or neutrophil function and was possibly brought about by the inhibition of bacterial growth.
In-vitro evaluation of nitrofurantoin as an alternative agent for metronidazole in combination antimicrobial therapy against Helicobacter pylori (1998)

Increasing metronidazole resistance suggests the need for alternative antibiotics for combination therapy of Helicobacter pylori infections. We evaluated a metronidazole-resistant and a clarithromycin-resistant strain of H. pylori under stationary growth phase conditions that favoured physiological conditions in order to determine if nitrofurantoin might be a suitable alternative for metronidazole in combination therapy. The results demonstrated that the triple combination of bismuth, tetracycline and nitrofurantoin achieved greater bactericidal activity against these two strains than did the combination of bismuth, tetracycline and metronidazole. These results suggest that further evaluation is warranted.
Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise (2015)

Skeletal muscles comprise a substantial portion of whole body mass and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength-related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi-faceted involving both intrinsic age-related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of 'anabolic resistance' to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance- and aerobic-type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle-loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. essential amino acid/leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits, that is physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age.