gebhart/patrepeval huggingface dataset:
Activation of the ATR-mediated DNA Damage Response by the HIV-1 Viral Protein R (2003)

DNA damage is a universal inducer of cell cycle arrest at the G2 phase. Infection by the human immunodeficiency virus type 1 (HIV-1) also blocks cellular proliferation at the G2 phase. The HIV-1 accessory gene vpr encodes a conserved 96-amino acid protein (Vpr) that is necessary and sufficient for the HIV-1-induced block of cellular proliferation. In the present study, we examined a recently identified DNA damage-signaling protein, the ATM- and Rad3-related protein, ATR, for its potential role in the induction of G2 arrest by Vpr. We show that inhibition of ATR by pharmacological inhibitors, by expression of the dominant-negative form of ATR, or by RNA interference inhibits Vpr-induced cell cycle arrest. As with DNA damage, activation of ATR by Vpr results in phosphorylation of Chk1. This study provides conclusive evidence of activation of the ATR-initiated DNA damage-signaling pathway by a viral gene product. These observations are important toward understanding how HIV infection promotes cell cycle disruption, cell death, and ultimately, CD4+ lymphocyte depletion.
Asymmetric Michael Addition of Arylthiols to α,β‐Unsaturated Carbonyl Compounds Catalyzed by Bifunctional Organocatalysts. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Can Monitoring of Intrathoracic Impedance Reduce Morbidity and Mortality in Patients with Chronic Heart Failure? Rationale and Design of the Diagnostic Outcome Trial in Heart Failure (DOT-HF) (2008)

Approximately 2400 patients will be randomised in a 1:1 fashion to a management strategy with access to the diagnostic information from the implantable device ("access arm"), or a "control arm", where this information is not made available. Study subjects fulfil standard indications for CRT and/or ICD as outlined in current guidelines. In the access arm, a fluid alert algorithm is used to give early warning of decreasing intrathoracic impedance indicating a high risk of an impending volume-overload decompensation. The primary endpoint of DOT-HF is the composite of all-cause mortality or heart failure hospitalisation. Secondary and exploratory endpoints include all-cause mortality, the impact on total health care utilization, quality of life and cost effectiveness. The study is expected to close recruitment during 2010 and to report in 2012.
The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer (2014)

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription.
3D Electron Diffraction: The Nanocrystallography Revolution (2019)

Crystallography of nanocrystalline materials has witnessed a true revolution in the past 10 years, thanks to the introduction of protocols for 3D acquisition and analysis of electron diffraction data. This method provides single-crystal data of structure solution and refinement quality, allowing the atomic structure determination of those materials that remained hitherto unknown because of their limited crystallinity. Several experimental protocols exist, which share the common idea of sampling a sequence of diffraction patterns while the crystal is tilted around a noncrystallographic axis, namely, the goniometer axis of the transmission electron microscope sample stage. This Outlook reviews most important 3D electron diffraction applications for different kinds of samples and problematics, related with both materials and life sciences. Structure refinement including dynamical scattering is also briefly discussed.
Successful treatment of therapy-resistant atopic dermatitis with clobetasol propionate and a hydrocolloid occlusive dressing. (1992)

During recent years, 48 patients with therapy-resistant chronic skin lesions of atopic dermatitis have been treated once a week with clobetasol propionate lotion left under Duoderm occlusive patches. They had previously failed to respond, or responded only sparsely, to topical corticosteroids. The lesions resolved completely in 44 patients, while partial remission was observed in the remaining 4. The mean time needed to obtain complete remission was, for lichenifications, 2 weeks; pruriginous lichenoid papules, 12 days; chronic hand eczema, 2.5 weeks; nummular eczema, 8 days; perioral eczema, 11 days, and breast eczema, 10 days. Adverse experiences were mild and infrequent. The amount of topical corticosteroid required was reduced to at most one-twentieth and to as little as one-hundredth of the amount of common topical steroid treatment needed. We conclude that clobetasol propionate and Duoderm once a week is the best treatment for resistant lesions of atopic dermatitis.
New <i>Secale cereale</i> (rye) DNA derivatives for the detection of rye chromosome segments in wheat (1990)

Subcloning of a clone of the 120-bp family of rye, pSc119, has produced two extremely useful probes. pSc119.1 assays rye-specific dispersed repetitive sequence families. It is present on all seven rye chromosomes and hybridizes to the entire length of each chromosome, with the exception of some telomeres and the nucleolar organiser region. pSc119.2, in contrast, hybridizes predominantly to the telomeric regions of rye chromosomes, with some interstitial sites. Unlike pSc119.1, it assays similar repetitive sequence families in both wheat and rye chromosomes.
Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis (2017)

ClinicalTrials.gov Identifier: NCT01230424.
Sociocultural Aspects of Tuberculosis Control in Ethiopia (1997)

This article examines ethnomedical knowledge and practices related to tuberculosis conceptualization and management in a rural southern Ethiopian community. An adult health-status survey, administered to 217 adults selected through quota sampling procedures, investigated prevailing nosological structures. Additionally, disease-enhancing behaviors were identified through qualitative-research methods. The findings show that while symptomatological concepts coincide with biomedicine, the local etiological model postulates empirically based causational factors unrelated to tubercle bacilli. Therapeutic preference hinges on the utilization of ethnobotanical remedies and their expected emetic effects. The relevance of tuberculosis-related ethnomedical knowledge and management practices is discussed in relation to primary health care and disease-control programs in Ethiopia. It is recommended that health-education interventions, illustrating the nature and transmission avenues of tuberculosis and the effects of biomedical therapies, precede and/or accompany vaccination campaigns or chemotherapy. Teaching materials should valorize existing ethnomedical notions that emphasize contagion as an avenue of disease transmission, and the importance of nutritional adequacy in fighting the disease.
유전 및 육종 : 홀스타인 젖소의 체형형질과 생산형질들에 대한 유전모수 추정 (1996)

This study utilized 9,881 records of linear type scores consisting of 15 primary traits and 12,304 production records of Holsteins from 1984 to 1995 in Korea to estimate genetic parameters for production and type traits using animal models. The results obtained were as follows:1. The heritabilities for type traits prior to 1990 was higher than those after 1990. The heritabilities for body type and udder traits ranged from 0.101 to 0.209 and from 0.082 to 0.281 respectively. 2. The means of rear udder height and rear udder width were 21.56 and 20.25cm. These results suggested that ganetic improvement of these traits should be needed. The skewedness for type traits was not proper, more accurate measurement for type trait is required. 3. General appearances which had the highest genetic correlation with udder traits were dairy foam, sump angle, and rump width. The udder depth had the highest ganetic correlation with fore udder attachment and body depth. 4. All of the type traits except for rump angle and udder cleft had positive genetic correlations with final score, and rear udder width had the highest ganetic correlation with final score. 5. The heritabilities for milk and milkfat were 0.278 and 0.194, and the repeatabilities for these traits were 0.467 and 0.434. 6. The order of type traits which had the highest genetic correlation with production traits was rear udder height, rear udder width, dairy form and final score.
Synthesis of Tetracyclic Heterocompounds as Selective Estrogen Receptor Modulators. Part 2. Process Improvement for Scale-Up Of 2,5,8-Substituted 11,12-Dihydro-5<i>H</i>-6,13-dioxabenzo[3,4]cyclohepta-[1,2-<i>a</i>]naphthalene Derivatives (2007)

An improved, reproducible nonchromatographic process for scale-up synthesis of 2,5,8-substituted 11,12-dihydro-5H-6,13-dioxabenzo[3,4]cyclohepta[1,2-a]naphthalene derivatives as selective estrogen receptor modulators (SERMs) is described. The titled compounds were prepared in 9−21% overall yield with high chemical purity (>97%) after nine consecutive synthetic steps.
IRBL: An Implicitly Restarted Block-Lanczos Method for Large-Scale Hermitian Eigenproblems (2003)

The irbleigs code is an implementation of an implicitly restarted block-Lanczos method for computing a few selected nearby eigenvalues and associated eigenvectors of a large, possibly sparse, Hermitian matrix A. The code requires only the evaluation of matrix-vector products with A; in particular, factorization of A is not demanded, nor is the solution of linear systems of equations with the matrix A. This, together with a fairly small storage requirement, makes the irbleigs code well suited for large-scale problems. Applications of the irbleigs code to certain generalized eigenvalue problems and to the computation of a few singular values and associated singular vectors are also discussed. Numerous computed examples illustrate the performance of the method and provide comparisons with other available codes.
Pyroglutamate Formation Influences Solubility and Amyloidogenicity of Amyloid Peptides (2009)

N-Terminally truncated and pyroglutamate (pGlu) modified amyloid beta (Abeta) peptides are major constituents of amyloid deposits in sporadic and inherited Alzheimer's disease (AD). Formation of pGlu at the N-terminus confers resistance against cleavage by most aminopeptidases, increases toxicity of the peptides, and may seed Abeta aggregate formation. Similarly, the deposited amyloid peptides ABri and ADan, which cause a very similar histopathology in familial British dementia (FBD) and familial Danish dementia (FDD), are N-terminally blocked by pGlu. Triggered by the coincidence of pGlu-modified amyloid peptides and similar pathology in AD, FBD, and FDD, we investigated the impact of N-terminal pGlu on biochemical and biophysical properties of Abeta, ABri, and ADan. N-Terminal pGlu increases the hydrophobicity and changes the pH-dependent solubility profile, rendering the pGlu-modified peptides less soluble in the basic pH range. The pGlu residue increases the aggregation propensity of all amyloid peptides as evidenced by ThT fluorescence assays and dynamic light scattering. The far-UV CD spectroscopic analysis points toward an enhanced beta-sheet structure of the pGlu-Abeta. Importantly, changes in fibril morphology are clearly caused by the N-terminal pGlu, resulting in the formation of short fibers, which are frequently arranged in bundles. The effect of pGlu on the morphology is virtually indistinguishable between ABri, ADan, and Abeta. The data provide evidence for a comparable influence of the pGlu modification on the aggregation process of structurally different amyloid peptides, thus likely contributing to the molecularly distinct neurodegenerative diseases AD, FBD, and FDD. The main driving force for the aggregation is apparently an increase in the hydrophobicity and thus an accelerated seed formation.
A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2‐Arachidonoylglycerol (2008)

The endocannabinoid system is the signaling network hijacked by the active component of marijuana, tetrahydrocannibinol (THC), which elicits its effects by activating the cannabinoid (CB) receptors. The endogenous ligands of the CB receptors (“endocannabinoids”) include the lipid transmitters anandamide and 2‐arachidonoyl glycerol (2‐AG). Endocannabinoids have been implicated a wide range of physiological processes including appetite, pain, anxiety and cognition. Endocannabinoid levels in the central nervous system are tightly controlled by enzymatic biosynthesis and degradation. Inactivation of anandamide by fatty acid amide hydrolase (FAAH) has been well characterized, but less is known about the degradation of 2‐AG, which can be hydrolyzed by multiple enzymes in vitro including FAAH and monoacylglyceride lipase (MAGL). We adopted a functional proteomic strategy including activity‐based protein profiling (ABPP) and pharmacological inhibition studies to comprehensively profile 2‐AG hydrolases in the mouse brain. Our results reveal that ~85% of 2‐AG hydrolase activity in mouse brain membranes is performed by MAGL, with the remaining ~15% being catalyzed by two previously uncharacterized enzymes ABHD6 and ABHD12. We determined that MGL, ABHD6, and ABHD12 occupy distinct subcellular localizations, suggesting that they may be responsible for regulating distinct pools of 2‐AG in the nervous system. This work was supported by the National Institutes of Health grants DA015197 and DA017259 (B.F.C), a Fletcher Jones Foundation Scholarship (J.L.B.), the Daniel Koshland Fellowship in Enzyme Biochemistry (G.M.S.), the Skaggs Institute for Chemical Biology, and the Helen L. Dorris Institute for the Study of Neurological and Psychiatric Disorders of Children and Adolescents.
Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors from <i>Morinda citrifolia</i> (Noni) and Their Insulin Mimetic Activity (2013)

As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.
Inhibitory action of insulin‐sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea‐pig (1998)

1. The actions of troglitazone, pioglitazone, metformin and bezafibrate, agents that improve insulin-resistance, on voltage-dependent Ca2+ channels in arterial smooth muscle cells were examined by use of the conventional and nystatin-perforated whole-cell clamp methods. Single cells were freshly isolated from resistance mesenteric arteries of guinea-pigs. The actions of these agents on 77 mM K+-induced contraction of the isolated arteries were also examined with the use of isometric tension recording. 2. The thiazolidinedione derivatives, troglitazone and pioglitazone, inhibited whole-cell Ca2+ currents in a dose-dependent manner with dissociation constants of 3.0 microM and 44.9 microM and Hill coefficients of 0.61 and 0.68, respectively. These two agents inhibited the 77 mM K+-induced contraction with similar potencies as those inhibiting the Ca2+ currents. Metformin and bezafibrate had no apparent effects on the Ca2+ current or high K+-induced contraction. 3. The inhibitory action of troglitazone on Ca2+ currents was not affected by the command potential, the holding potential, or the stimulation frequency, suggesting that its mode of the action differs from that of known organic Ca2+ channel antagonists. 4. The inhibitory action of troglitazone on Ca2+ currents was not affected by the addition of insulin to, or the removal of glucose from, the solutions. 5. In conclusion, the thiazolidinedione derivatives directly inhibited the voltage-dependent Ca2+ channels in a different manner from that of organic Ca2+ channel antagonists. This inhibitory action on Ca2+ channels was not a common feature of insulin-sensitizing agents.
Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis (2007)

This meta-analysis shows a clear association between exposure to antibiotics and MRSA isolation. This information may be useful for researchers in designing future studies and for policy decision-making on the appropriate management of antibiotic therapies.
Modeling the detailed kinetics of mitochondrial cytochrome<i>c</i>oxidase: Catalytic mechanism and nitric oxide inhibition (2016)

Cytochrome c oxidase (CcO) catalyzes the exothermic reduction of O<sub>2</sub> to H<sub>2</sub>O by using electrons from cytochrome c, and hence plays a crucial role in ATP production. Although details on the enzyme structure and redox centers involved in O<sub>2</sub> reduction have been known, there still remains a considerable ambiguity on its mechanism of action, e.g., the number of sequential electrons donated to O<sub>2</sub> in each catalytic step, the sites of protonation and proton pumping, and nitric oxide (NO) inhibition mechanism. In this work, we developed a thermodynamically constrained mechanistic mathematical model for the catalytic action of CcO based on available kinetic data. The model considers a minimal number of redox centers on CcO and couples electron transfer and proton pumping driven by proton motive force (PMF), and accounts for the inhibitory effects of NO on the reaction kinetics. The model is able to fit well all the available kinetic data under diverse experimental conditions with a physiologically realistic unique parameter set. The model predictions show that: 1) the apparent K<sub>m</sub> of O<sub>2</sub> varies considerably and increases from fully reduced to fully oxidized cytochrome c depending on pH and the energy state of mitochondria, and 2) the intermediate enzyme states depend on pH and cytochrome c redox fraction and play a central role in coupling mitochondrial respiration to PMF. The developed CcO model can easily be integrated into existing mitochondrial bioenergetics models to understand the role of the enzyme in controlling oxidative phosphorylation in normal and disease conditions.
Multiple access interference plus noise constrained least mean square algorithm (2008)

In this work, a constrained least-mean-square (LMS) algorithm, which incorporates the knowledge of the number of users, spread-ing sequence length and additive noise variance, is developed sub-ject to the new combined constraint comprising both the MAI and noise variance. The novelty of this constraint resides in the fact that the MAI variance was never used as a constraint. This con-strained optimization technique results in an (MAI plus noise)-constrained LMS (MNCLMS) algorithm. Convergence analysis is carried out of the proposed algorithm in the presence of MAI. Fi-nally, a number of simulations are conducted to compare perfor-mance of MNC-LMS algorithm with other adaptive algorithms. 1.
Application of multigrid technique to the spatial network method (1991)

Abstract Recently, with the rapid development in the speed and memory of digital computers, simulation has become available in many fields. However, huge calculation is required to acquire good accuracy and an efficient method of calculation should be used so that the time and memory limitations of the computers may be utilized effectively. The authors have already applied the spatial network method to many electromagnetic problems to find the three‐dimensional time response including the transient response. In this method, basically, the region of analysis is divided into equal intervals. However, when the whole region of analysis is divided into equal intervals, the spatial difference interval should be fixed in such a way that the smallest part of the region may be expressed correctly. Hence, for the analysis models including a thin slab, a large number of variables and, consequently, a large amount of memory are involved. To overcome this problem, this paper introduces the application of the multigrid technique to the spatial network method where the division of a part of the region can be refined further. The validity of this method is checked by analyzing the dielectric‐loaded rectangular waveguide.
Reformatsky Reaction on Aroylketene<i>S</i>,<i>N</i>-Acetals: A Facile Route to 4-Amino-6-aryl-2<i>H</i>-pyran-2-ones (1988)

The aroylketene S,N-acetals 1a-j are shown to undergo regioselective conjugate 1,4-addition with Reformatsky reagent derived from ethyl bromoacetate, followed by cyclization to give novel 4-amino-6-aryl-2H-pyran-2-ones 3a-j in good yields.
A versatile strategy for the derivatisation of the carboxy group of amphotericin B: the preparation of C-16 ketone analogues (1992)

M. J. Driver, A. R. Greenlees and D. T. MacPherson, J. Chem. Soc., Perkin Trans. 1, 1992, 3155 DOI: 10.1039/P19920003155
The Potential of Statins for Buccal Delivery (2014)

Statins minimize the endogenous synthesis of cholesterol preventing the onset and development of artherosclerosis and are therefore used as an effective treatment against primary hypercholesterolemia. Statins do exhibit antiinflammatory, vasculoprotective, and antioxidant effects. The promising delivery of statins across the buccal mucosa poses a continuing challenge as well as a great opportunity. Buccal delivery has progressed far beyond the use of traditional dosage forms with novel approaches emerging continuously. Buccal drug delivery system in which drug enters directly in systemic circulation thereby by passing the first pass effect. The buccal route has been researched for a wide variety of drugs and has gained significant attention and momentum since it offers remarkable advantages. Buccal adhesive systems offer innumerable advantages in terms of accessibility, administration and withdrawal, retentivity, enhanced bioavailability, avoid first pass effect. At the current global scenario, scientists are finding ways to develop buccal adhesive systems through various approaches to improve the bioavailability of antihyperlipidemic drugs by manipulation of the formulation strategies like inclusion of pH modifiers, enzyme inhibitors, permeation enhances. This review highlights the buccal delivery approaches of statins.