gebhart/patrepeval huggingface dataset:
Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats (2012)

These findings demonstrate that Leu content is a critical factor for evaluating the quantity and quality of proteins necessary at a meal for stimulation of MPS.
Solubilizing Coelenterazine in Water with Hydroxypropyl-β-cyclodextrin (1997)

Coelenterazine is poorly soluble in water except at alkaline pH values that promote auto-oxidation. The solubility is markedly increased by adding hydroxypropyl-p-cyclodextrin in a neutral buffer solution, the solubilization being most effective in the pH range of 6.5 to 7.0. The concentration of coelenterazine dissolved in a pH 7.0 buffer containing 50 mM hydroxypropyl-p-cyclodextrin was about 280-fold higher than that without the additive.
Visualization and Spectroscopy of a Metal-Molecule-Metal Bridge (2003)

Artificial nanostructures, each composed of a copper(II) phthalocyanine (CuPc) molecule bonded to two gold atomic chains with a controlled gap, were assembled on a NiAl(110) surface by manipulation of individual gold atoms and CuPc molecules with a scanning tunneling microscope. The electronic densities of states of these hybrid structures were measured by spatially resolved electronic spectroscopy and systematically tuned by varying the number of gold atoms in the chains one by one. The present approach provides structural images and electronic characterization of the metal-molecule-metal junction, thereby elucidating the nature of the contacts between the molecule and metal in this junction.
Global Analysis of Smad2/3-Dependent TGF-β Signaling in Living Mice Reveals Prominent Tissue-Specific Responses to Injury (2005)

Smad2 and Smad3 (Smad2/3) proteins are key signaling molecules for TGF-beta and some related family members regulating the transcription of several hundred genes. TGF-beta have key roles in development, tissue homeostasis, and the pathogenesis of many human diseases, including cancer, fibrotic disorders, developmental defects, and neurodegeneration. To study the temporal and spatial patterns of Smad2/3-dependent signaling in normal and pathological conditions in the living organism, we engineered transgenic mice with a Smad-responsive luciferase reporter construct (SBE-luc mice). Using bioluminescent imaging, we assessed Smad2/3 signaling activity noninvasively in living mice. At baseline, this activity was highest in brain, intestine, heart, and skin, and correlated with biochemical measurements of reporter activity. Primary astrocytes cultured from SBE-luc mice showed specific activation of the reporter in response to Smad2/3-activating TGF-beta family members. Treatment of mice with the endotoxin LPS resulted in a fast and vigorous, but transient activation of the reporter in the intestine. Although the response was similarly rapid in brain, it remained increased, indicating important but different cellular responses to endotoxin challenge in these organs. Traumatic brain injury with a needle stab resulted in local activation of Smad2/3-dependent genes and a severalfold increase in bioluminescence in living mice. SBE-luc mice can therefore be used to study temporal, tissue-specific activation of Smad2/3-dependent signaling in living mice in normal or pathological conditions as well as for the identification of endogenous or synthetic modulators of this pathway.
Genotyping Single Nucleotide Polymorphisms by Multiplex Minisequencing Using Tag-Arrays (2009)

The need for multiplexed methods for SNP genotyping has rapidly increased during the last decade. We present here a flexible system that combines highly specific genotyping by minisequencing single-base extension with the advantages of a microarray format that allows highly multiplexed and parallel analysis of any custom selected SNPs.Cyclic minisequencing reactions with fluorescently labeled dideoxynucleotides (ddNTPs) are performed in solution using multiplex PCR product as template and detection primers, designed to anneal immediately adjacent and upstream of the SNP site. The detection primers carry unique Tag-sequences at their 5' ends and oligonucleotides complementary to the Tag-sequence, cTags, are immobilized on a microarray. After extension, the tagged detection primers are allowed to hybridize to the cTags, and the fluorescent signals from the array are measured and the genotypes are deduced by cluster analysis of the incorporated labels. The "array of arrays" format of the system, accomplished by a silicon rubber grid to form separate reaction chambers, allows either 80 or 16 samples to be analyzed for up to 200 or 600 SNPs, respectively on a single microscope slide.
Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint (2000)

Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes. By gene disruption, we show that CHK1 deficiency results in a severe proliferation defect and death in embryonic stem (ES) cells, and peri-implantation embryonic lethality in mice. Through analysis of a conditional CHK1-deficient cell line, we demonstrate that ES cells lacking Chk1 have a defective G(2)/M DNA damage checkpoint in response to gamma-irradiation (IR). CHK1 heterozygosity modestly enhances the tumorigenesis phenotype of WNT-1 transgenic mice. We show that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU). Overexpression of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced by UV treatment. Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1.
Synthesis and Antifouling Activity of 3‐Isocyanotheonellin and Its Analogues. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Fabrication and applications of large arrays of multifunctional rolled-up SiO/SiO2microtubes (2011)

Biocompatible, multifunctional large arrays of transparent SiO/SiO2 microtubes are fabricated by rolled-up nanotech. The outer tubular diameter as a function of thicknesses of SiO and SiO2 has been systematically studied and the roll-up parameters have been optimized to deterministically achieve a yield of nearly 100%. A macroscopic continuum mechanical model is in good agreement with the experimental data. The relative ease in functionalization of the “glass” microtubes with different biomaterials renders rolled-up nanotech an excellent option for various on- and off-chip applications, including optofluidic sensors, micro-engines and pre-patterned 3D scaffolds for cell culturing.
Acid-based hydrolysis processes for ethanol from lignocellulosic materials: A review (2007)

Bioethanol is nowadays one of the main actors in the fuel market. It is currently produced from sugars and starchy materials, but lignocelluloses can be expected to be major feedstocks for ethanol production in the future. Two processes are being developed in parallel for conversion of lignocelluloses to ethanol, “acid-based” and “enzyme-based” processes. The current article is dedicated to review of progress in the “acid-based-hydrolysis” process. This process was used industrially in the 1940s, during wartime, but was not economically competitive afterward. However, intensive research and development on its technology during the last three decades, in addition to the expanding ethanol market, may revive the process in large scale once again. In this paper the ethanol market, the composition of lignocellulosic materials, concentrated- and dilute-acid pretreatment and hydrolysis, plug-flow, percolation, counter-current and shrinking-bed hydrolysis reactors, fermentation of hexoses and pentoses, effects of fermentation inhibitors, downstream processing, wastewater treatment, analytical methods used, and the current commercial status of the acid-based ethanol processes are reviewed.
Longitudinal Assessment of Cytomegalovirus (CMV)–Specific Immune Responses in Liver Transplant Recipients at High Risk for Late CMV Disease (2007)

Cytomegalovirus (CMV)-seronegative recipients (R(-)) of a liver transplant from CMV-positive donors (D(+)) are at high risk for developing late CMV disease after discontinuation of antiviral prophylaxis. Levels of viremia and CMV-specific interferon (IFN)- gamma -producing CD4(+) and IFN- gamma -producing CD8(+) T cell responses were prospectively measured from discontinuation of antiviral prophylaxis until 1 year after transplantation in 17 consecutive D(+)/R(-) patients. CMV loads of >1000 copies/mL were strongly associated with CMV disease in the 6 symptomatic patients. Despite immunosuppression, broadly diverse T cells specific for CMV lysate or peptide libraries spanning pp65 and immediate early (IE) 1 immunodominant CMV antigens developed in all patients. A vigorous CD8(+) T cell response to pp65 and IE1 antigens characterized the D(+)/R(-) cohort. Unexpectedly, none of these responses were predictive of CMV disease or viremia. No significant lymphopenia or functional impairment of CMV-specific T cells was detected in the symptomatic patients, whose morbidity was resolved after antiviral treatment while measurable CMV immunity was maintained during the 1-year observation period.
Elevated serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer (2005)

Despite improved results gained by the combination of neoadjuvant chemotherapy and radiotherapy with surgery, the prognosis for the esophageal carcinoma patient remains poor. There is a need for prognostic markers that can help improve patient selection. The aim of this study was to evaluate whether serum levels of C-reactive protein (CRP) have any influence on the patient prognosis in terms of prediction of chemoradiosensibility, and overall and disease-free survival. Blood samples were obtained at the time of diagnosis in 67 patients with biopsy-proven primary carcinoma of the esophagus. Although not significantly, the mean CRP level was higher than that of 20 patients with benign esophageal pathology who served as controls. No significant correlation could be found between CRP levels and baseline characteristics such as age, gender, histology, cancer localization, tumor depth, lymph node status or metastatic spread. However, patients with CRP levels higher than 6 mg/L were more frequently non-responders to chemoradiotherapy (P = 0.035), had a shorter overall survival (P = 0.061) and a shorter disease-free survival (P = 0.016). It is concluded from these results that pretreatment measurement of serum CRP levels in patients with esophageal cancer could to be used in routine practice as indicators of chemoradiosensibility and prognosis.
An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3-mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation. (1991)

The synthetic peptide Gly-Arg-Gly-Asp-Tyr (GRGDY), which contains the RGD sequence of several adhesion molecules, was covalently grafted to the surface of otherwise poorly adhesive glass substrates and was used to determine the minimal number of ligand-receptor interactions required for complete spreading of human foreskin fibroblasts. Well-defined adhesion substrates were prepared with GRGDY between 10(-3) fmol/cm2 and 10(4) fmol/cm2. As the adhesion ligand surface concentration was varied, several distinct morphologies of adherent cells were observed and categorized. The population of fully spread cells at 4 h reached a maximum at 1 fmol/cm2, with no further increases up to 10(4) fmol/cm2. Although maximal cell spreading was obtained at 1 fmol/cm2, focal contacts and stress fibers failed to form at RGD surface concentrations below 10 fmol/cm2. The minimal peptide spacings obtained in this work correspond to 440 nm for spreading and 140 nm for focal contact formation, and are much larger than those reported in previous studies with adsorbed adhesion proteins, adsorbed RGD-albumin conjugates, or peptide-grafted polyacrylamide gels. Vitronectin receptor antiserum specific for integrin alpha V beta 3 blocked cell adhesion and spreading on substrates containing 100 fmol/cm2 of surface-bound GRGDY, while fibronectin receptor antiserum specific for alpha 5 beta 1 did not. Furthermore, alpha V beta 3 was observed to cluster into focal contacts in spread cells, but alpha 5 beta 1 did not. It was thus concluded that a peptide-to-peptide spacing of 440 nm was required for alpha V beta 3-mediated cellular spreading, while 140 nm was required for alpha V beta 3-mediated focal contact formation and normal stress fiber organization in human foreskin fibroblasts; these spacings represent much fewer ligands than were previously thought to be required.
A New Approach to Automatic History Matching Using Kernel PCA (2007)

Abstract Efficient history matching of geologically complex reservoirs is important in many applications, but it is central in closed-loop reservoir modeling, in which real-time model updating is required. Within the context of closed-loop reservoir modeling, the two approaches receiving the most attention to date are ensemble Kalman filtering and gradient-based methods using Karhunen-Loeve representations (eigen-decomposition) of the permeability field. Both of these procedures are technically appropriate only for random fields (e.g., permeability) characterized by two-point geostatistics (multi-Gaussian random fields). Realistic systems are much better described by multipoint geostatistics, which is capable of representing key geological structures such as channels. History matching algorithms that are able to reproduce realistic geology provide enhanced predictive capacity and are therefore more suitable for use with field optimization. In this work, we apply a new parameterization, referred to as a kernel principal component analysis (kernel PCA or KPCA) representation, to model permeability fields characterized by multipoint geostatistics. Kernel PCA enables preserving arbitrarily high order statistics of random fields, thereby providing the capability to reproduce complex geology. The KPCA representation is then combined with an efficient gradient-based history matching technique. The linkage of KPCA for modeling geology with gradient-based history matching is very natural as the KPCA representation is differentiable and gradients with respect to geological parameters can be readily computed. The overall procedure is then applied to several example cases, including synthetic models and a model of a real reservoir. The approach is shown to better reproduce complex geology, which leads to improved history matches and better predictions, while retaining reasonable computational requirements.
Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase (2007)

The glucose transporter GLUT4 and the aminopeptidase IRAP (insulin-responsive aminopeptidase) are the major cargo proteins of GSVs (GLUT4 storage vesicles) in adipocytes and myocytes. In the basal state, most GSVs are sequestered in perinuclear and other cytosolic compartments. Following insulin stimulation, GSVs undergo exocytic translocation to insert GLUT4 and IRAP into the plasma membrane. The mechanisms regulating GSV trafficking are not fully defined. In the present study, using 3T3-L1 adipocytes transfected with siRNAs (small interfering RNAs), we show that insulin-stimulated IRAP translocation remained intact despite substantial GLUT4 knockdown. By contrast, insulin-stimulated GLUT4 translocation was impaired upon IRAP knockdown, indicating that IRAP plays a role in GSV trafficking. We also show that knockdown of tankyrase, a Golgi-associated IRAP-binding protein that co-localizes with perinuclear GSVs, attenuated insulin-stimulated GSV translocation and glucose uptake without disrupting insulin-induced phosphorylation cascades. Moreover, iodixanol density gradient analyses revealed that tankyrase knockdown altered the basal-state partitioning of GLUT4 and IRAP within endosomal compartments, apparently by shifting both proteins toward less buoyant compartments. Importantly, the afore-mentioned effects of tankyrase knockdown were reproduced by treating adipocytes with PJ34, a general PARP (poly-ADP-ribose polymerase) inhibitor that abrogated tankyrase-mediated protein modification known as poly-ADP-ribosylation. Collectively, these findings suggest that physiological GSV trafficking depends in part on the presence of IRAP in these vesicles, and that this process is regulated by tankyrase and probably its PARP activity.
Roles of the Different Isozymes and Salivary Factors in the Maintenance of Optimal Conditions in the Gastrointestinal Canal (1996)

(1996). Roles of the Different Isozymes and Salivary Factors in the Maintenance of Optimal Conditions in the Gastrointestinal Canal. Scandinavian Journal of Gastroenterology: Vol. 31, No. 4, pp. 305-317.
A Multi-Compartment Single and Multiple Dose Pharmacokinetic Comparison of Rectally Applied Tenofovir 1% Gel and Oral Tenofovir Disoproxil Fumarate (2014)

This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blood, colonic biopsies and rectal and vaginal mucosal fluids were collected after the single oral TDF, the single topical TFV gel dose, and after 7 days of topical TFV gel dosing for extracellular analysis of TFV and intracellular analysis of the active metabolite tenofovir diphosphate (TFVdp) in peripheral blood mononuclear cells (PBMCs) and isolated mucosal mononuclear cells (MMC), including CD4+ and CD4- cell subsets. With a single rectal dose, TFV plasma concentrations were 24–33 fold lower and half-life was 5 h shorter compared to a single oral dose (p = 0.02). TFVdp concentrations were also undetectable in PBMCs with rectal dosing. Rectal tissue exposure to both TFV and TFVdp was 2 to 4-log10 higher after a single rectal dose compared to a single oral dose, and after 7 daily doses, TFVdp accumulated 4.5 fold in tissue. TFVdp in rectal tissue homogenate was predictive (residual standard error, RSE = 0.47) of tissue MMC intracellular TFVdp concentration, with the CD4+ cells having a 2-fold higher TFVdp concentration than CD4- cells. TFV concentrations from rectal sponges was a modest surrogate indicator for both rectal tissue TFV and TFVdp (RSE = 0.67, 0.66, respectively) and plasma TFV (RSE = 0.38). TFV penetrates into the vaginal cavity after oral and rectal dosing, with rectal dosing leading to higher vaginal TFV concentrations (p<0.01). Trial registration: ClinicalTrials.gov NCT00984971.
The Diagnosis and Management of Mild Cognitive Impairment (2014)

Cognitive decline and MCI have important implications for patients and their families and will require that primary care clinicians be skilled in identifying and managing this common disorder as the number of older adults increases in coming decades. Current evidence supports aerobic exercise, mental activity, and cardiovascular risk factor control in patients with MCI.
Characterization of a positive regulatory element in the mts1 gene. (1993)

The first intron of the mts1 gene, a gene that is selectively expressed in metastatic cells and in normal cells that are motile, was found to be highly homologous to the CD3 delta enhancer element. Because of the homology between the CD3 delta enhancer and the first intron of mts1, we analysed the first intron of the mts1 gene to determine whether it functions as a transcriptional regulatory element. Highly metastatic CSML-100 cells transfected with chloramphenicol acetyl transferase-containing plasmids demonstrated the ability of the mts1 first intron to function as a positive regulatory element. In vitro footprinting analysis using extracts from CSML-0 cells (which express mts1 at low levels) or CSML-100 cells (which express mts1 at high levels) identified a protected 16-nucleotide element in the first intron of mts1, regardless of the extract used. However, in vivo footprinting analysis of the same region identified the protected 16-nucleotide fragment only in the mts1 intron from CSML-100 cells, not from CSML-0 cells. Differences in the methylation pattern of the mts1 gene in CSML-100 cells and CSML-0 cells are known to exist, and may in part be responsible for the mts1 footprinting differences observed in vivo from the different cell lines.
Permeation of water through polar and nonpolar polymers and copolymers: Determination of the concentration-dependent diffusion coefficient (2000)

The diffusion and permeation properties of liquid water through different polar and nonpolar polymers and copolymers were studied with a highly sensitive permeameter. The transient permeation fluxes through the polar polymer films could be fitted well only with an exponential equation for the diffusivity concentration dependence; this empirical exponential equation represented the diffusion plasticization effect of water on the materials. For the hydrophobic polyolefins, this exponential equation was no longer valid, and another form of the equation was empirically found to account for the reduction of the water diffusivity with the extent of the permeation. Such a negative plasticization effect might be attributed to the formation of water clusters in the polyolefins. The values of the diffusion coefficient of water in the dry polar polymers were smaller than those in dry polyolefins, but the opposite behavior was found for the permeability because it was much more favorable for water sorption in the polar polymers than in the hydrophobic polyolefins. For the ethylene–vinylacetate copolymers, the plasticization effect of water on its own diffusion was negative for the sample with a low vinyl acetate (VA) content; it became nil at 19 wt % VA and positive at higher VA contents. This increase in the extent of the water sorption with the increase in the VA content led to a steady increase in the water permeability in the poly(ethylene-co-vinylacetate) copolymers. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1998–2008, 2000
Is H3K4me3 instructive for transcription activation? (2016)

Tri-methylation of lysine 4 on histone H3 (H3K4me3) is a near-universal chromatin modification at the transcription start site of active genes in eukaryotes from yeast to man and its levels reflect the amount of transcription. Because of this association, H3K4me3 is often described as an 'activating' histone modification and assumed to have an instructive role in the transcription of genes, but the field is lacking a conserved mechanism to support this view. The overwhelming finding from genome-wide studies is that actually very little transcription changes upon removal of most H3K4me3 under steady-state or dynamically changing conditions, including at mammalian CpG island promoters. Instead, rather than a major role in instructing transcription, time-resolved experiments provide more evidence supporting the deposition of H3K4me3 into chromatin as a result of transcription, influencing processes such as memory of previous states, transcriptional consistency between cells in a population and transcription termination.