gebhart/patrepeval huggingface dataset:
Beta‐catenin regulates wound size and mediates the effect of TGF‐beta in cutaneous healing (2006)

After cutaneous injury, a variety of cell types are activated to reconstitute the epithelial and dermal components of the skin. beta-Catenin plays disparate roles in keratinocytes and fibroblasts, inhibiting keratinocyte migration and activating fibroblast proliferation, suggesting that beta-catenin could either inhibit or enhance the healing process. How beta-catenin functions in concert with other signaling pathways important in the healing process is unknown. Wound size was examined in mice expressing conditional null or conditional stabilized alleles of beta-catenin, regulated by an adenovirus expressing cre-recombinase. The size of the wounds in the mice correlated with the protein level of beta-catenin. Using mice expressing these conditional alleles, we found that the wound phenotype imparted by Smad3 deficiency and by the injection of TGFbeta before wounding is mediated in part by beta-catenin. TGFbeta was not able to regulate proliferation in beta-catenin null fibroblasts, whereas keratinocyte proliferation rate was independent of beta-catenin. When mice are treated with lithium, beta-catenin-mediated signaling was activated in cutaneous wounds, which healed with a larger size. These results demonstrate a crucial role for beta-catenin in regulating cutaneous wound size. Furthermore, these data implicate mesenchymal cells as playing a critical role regulating wound size.
Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia (2002)

The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL. It improved patients' CAD risk status significantly more than each drug alone.
Steering of optical beams using true-time delay based on the white cell (2005)

We propose a true-time delay approach for steering optical beams over wide angles (approaching /spl plusmn/57/spl deg/), without dispersion or sidelobes. A white cell with reflecting piston actuators provides delays from 1/500 to 3001.
Retinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region. (1994)

The Oct-3/4 gene product, which belongs to the POU family of transcription factors, is a good candidate for regulating initial differentiation decisions. It is expressed in the earliest stages of embryogenesis and repressed in subsequent stages. Retinoic acid (RA)-induced differentiation of embryonal carcinoma (EC) cells is accompanied by decreased expression of the Oct-3/4 gene. Previous findings show that sequences in the Oct-3/4 enhancer region (designated RARE1) are targets for RA-mediated repression (H. Okazawa, K. Okamoto, F. Ishino, T. Ishino-Kaneko, S. Takeda, Y. Toyoda, M. Muramatsu, and H. Hamada, EMBO J. 10:2997-3005, 1991). Our present results demonstrate conclusively that the TATA-less Oct-3/4 promoter is also a target for RA-induced repression. We identified a novel cis element in the Oct-3/4 promoter harbors a putative Sp1 binding site and a RA-responsive element (designated RAREoct), which are juxtaposed to one another. Protein binding to the Sp1 site is independent of protein binding to the RAREoct sequence. Unlike the RARE1 situated in the Oct-3/4 enhancer which does not contain a typical RAR recognition site, the RAREoct identified in this study consists of three directly repeated motifs that exhibit extensive homology to RARE sequences located in RA-responsive genes. Moreover, the RAREoct shows different DNA-binding characteristics and DNase I footprint patterns with nuclear proteins isolated from undifferentiated versus RA-differentiated EC cells. This suggests that the RAREoct element binds different nuclear proteins in RA-treated and untreated EC cells which most probably belong to the RA receptor, retinoid X receptor, or orphan receptor families of transcription factors. Using site-directed mutagenesis, we show that the RAREoct contributes to the transcriptional activation of Oct-3/4 promoter in P19 cells and, most interestingly, mediates the RA-induced repression in RA-differentiated EC cells. Thus, the RAREoct element could be one of the points of integration of several signalling pathways influencing Oct-3/4 expression. In accordance with the suggestion that suppression of Oct-3/4 expression is a crucial step during embryogenesis, the Oct-3/4 upstream region contains multiple targets for RA-induced repression, probably to ensure accurate and prompt repression of Oct-3/4 expression. It is possible that these repressors are differentially used at specific stages of development in response to various signals.
Global Surveillance for Antituberculosis-Drug Resistance, 1994–1997 (1998)

Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.
GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice (1990)

We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity.
Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily. (1989)

The leukocyte function-associated molecule 1 (LFA-1, CD11a/CD18) is a membrane glycoprotein which functions in cell-cell adhesion by heterophilic interaction with intercellular adhesion molecule 1 (ICAM-1). LFA-1 consists of an alpha subunit (Mr = 180,000) and a beta subunit (Mr = 95,000). We report the molecular biology and protein sequence of the alpha subunit. Overlapping cDNAs containing 5,139 nucleotides were isolated using an oligonucleotide specified by tryptic peptide sequence. The mRNA of 5.5 kb is expressed in lymphoid and myeloid cells but not in a bladder carcinoma cell line. The protein has a 1,063-amino acid extracellular domain, a 29-amino acid transmembrane region, and a 53-amino acid cytoplasmic tail. The extracellular domain contains seven repeats. Repeats V-VII are in tandem and contain putative divalent cation binding sites. LFA-1 has significant homology to the members of the integrin superfamily, having 36% identity with the Mac-1 and p150,95 alpha subunits and 28% identity with other integrin alpha subunits. An insertion of approximately 200 amino acids is present in the NH2-terminal region of LFA-1. This "inserted/interactive" or I domain is also present in the p150,95 and Mac-1 alpha subunits but is absent from other integrin alpha subunits sequenced to date. The I domain has striking homology to three repeats in human von Willebrand factor, two repeats in chicken cartilage matrix protein, and a region of complement factor B. These structural features indicate a bipartite evolution from the integrin family and from an I domain family. These features may also correspond to relevant functional domains.
Mechanism and specificity of succinyl-CoA:3-ketoacid coenzyme A transferase. (1976)

(a) The reactivity of substituted acetates as substrates for CoA transferase increases sharply with increasing basicity and exhibits a slope of 1.0 in a plot of either log kappacat or log (kappacat/Km) against pKa (betanuc = 1.0). This result shows that the catalyzed reaction, which involves both carboxylate activation and leaving group transfer, does not proceed through a fully concerted reaction mechanism in the rate-determining step. The result is consistent with a stepwise reaction mechanism that proceeds through an anhydride intermediate. (b) Equilibrium constants for thiol ester formation, either bound to the enzyme or free in solution, show the same dependence on the basicity of carboxylate ions (betaeq = 1.0) and are independent of acidity when expressed in terms of the carboxylic acid. Thus, the polar environment around substituents on the acyl group is the same for carboxylic acids, thiol esters, and oxygen esters. (c) The interaction of the terminal CH3CO group of acetoacetate with the active site causes a 200,000-fold increase in kappacat/Km, corresponding to a decrease in delta G++ OF 7.2 kcal/mol compared with an unsubstituted acid of the same pK. The binding energy of the coenzyme A moiety of the substrate is utilized to interact with the active site and cause a 10(4) to 10(6)-fold increase in kappacat, corresponding to a decrease in delta G++ of 6 to 9 kcal/mol, compared with fragments of the coenzyme A moiety added separatly or together. (d) The exchange of labeled coenzyme A into acyl-CoA substrates was found to be greater than or equal to 10(5) slower than substrate turnover.
Field-based angle-resolved light-scattering study of single live cells (2008)

We perform field-based angle-resolved light-scattering measurements from single live cells. We use a laser interferometer to acquire phase and amplitude images of cells at the image plane. The angular scattering spectrum is calculated from the Fourier transform of the field transmitted through the cells. A concurrent 3D refractive index distribution of the same cells is measured using tomographic phase microscopy. By measuring transient increases in light scattering by single cells during exposure to acetic acid, we correlate the scattering properties of single cells with their refractive index distributions and show that results are in good agreement with a model based on the Born approximation.
Proteome analysis of human colon cancer by two‐dimensional difference gel electrophoresis and mass spectrometry (2004)

Two-dimensional difference gel electrophoresis (2-D DIGE) coupled with mass spectrometry (MS) was used to investigate tumor-specific changes in the proteome of human colorectal cancers and adjacent normal mucosa. For each of six patients with different stages of colon cancer, Cy5-labeled proteins isolated from tumor tissue were combined with Cy3-labeled proteins isolated from neighboring normal mucosa and separated on the same 2-D gel along with a Cy2-labeled mixture of all 12 normal/tumor samples as an internal standard. Over 1500 protein spot-features were analyzed in each paired normal/tumor comparison, and using DIGE technology with the mixed-sample internal standard, statistically significant quantitative comparisons of each protein abundance change could be made across multiple samples simultaneously without interference due to gel-to-gel variation. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and tandem (TOF/TOF) MS provided sensitive and accurate mass spectral data for database interrogation, resulting in the identification of 52 unique proteins (including redundancies due to proteolysis and post-translationally modified isoforms) that were changing in abundance across the cohort. Without the benefit of the Cy2-labeled 12 sample mixture internal standard, 42 of these proteins would have been overlooked due to the large degree of variation inherent between normal and tumor samples.
An Immunohistochemical Analysis of Cytokine Expression in Allergic and Irritant Contact Dermatitis: Investigative Report (2000)

The purpose of this study was to investigate whether the specific and non-specific inflammatory responses to allergens and irritants give rise to immuno-histochemical detectable differences in the cytokine profile in the skin. Skin biopsies taken at 0, 6, 24 and 72 h from contact allergic reactions to nickel and from irritant reactions to sodium lauryl sulphate were analysed. The main finding was that the dermal cells expressed similar patterns of cytokines (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6 and IL-10) in both types of contact reaction at 72 h. However, two differences were observed. Staining for the IL-1 receptor antagonist was more prominent in the dermis at the late stages of the allergic reaction compared with the late stage of the irritant reaction. The other difference was an increased interferon-gamma staining of infiltrating mononuclear inflammatory cells in the dermis in the sodium lauryl sulphate group compared with the nickel group. A more rapid general onset of cytokine production was found in the sodium lauryl sulphate group than in the nickel group. The main conclusion of this study was that after 6 h the cytokine patterns did not differ between the specific and the non-specific inflammatory responses in the skin.
Effect of bcl-2 on Fas antigen-mediated cell death. (1993)

Fas Ag is a cell surface protein that can mediate apoptosis and belongs to the TNF receptor family. The product of protooncogene bcl-2, a membrane-associated protein, has been shown to inhibit apoptosis in various hematopoietic cells including B cells and T cells. To examine the possible interaction of the Fas Ag and bcl-2, we coexpressed human Fas Ag and bcl-2 cDNA in murine IL-3-dependent FDC-P1 cell line and murine lymphoma WR19L. FDC-P1 transformants expressing bcl-2 showed a prolonged survival to IL-3 depletion. FDC-P1 transformants expressing the Fas Ag alone were killed by anti-Fas antibody in the presence of IL-3. Overexpression of bcl-2 in FDC-P1 resulted in a partial inhibition of Fas-induced cell death. WR19L transformants expressing bcl-2 were partially resistant to the cytolytic activities of the TNF-alpha and anti-Fas antibody treatment. These results suggest that the Fas Ag and TNF receptor may share the same signaling pathway, and that bcl-2 interferes with the apoptotic process mediated by the Fas Ag and TNF receptor.
Substrate Recognition by Tissue Factor-Factor VIIa (1996)

Tissue factor (TF) is the protein cofactor for factor VIIa (FVIIa), the first serine protease of the clotting cascade. Previous studies using alanine mutagenesis have identified TF residues Lys165 and Lys166 as important for factor X (FX) activation, hypothesizing either that these residues interact with phospholipid head groups or that they directly or indirectly promote macromolecular substrate binding. In the recently reported x-ray crystal structure of the isolated extracellular domain of TF, both Lys165 and Lys166 are solvent-exposed and predicted to be near the phospholipid surface in intact TF. We hypothesized that these residues may in fact be ideally positioned to interact with the 4-carboxyglutamate-rich domain (Gla domain) of FX. We therefore predicted that mutations at Lys165 and Lys166 should have no effect on the activation of Gla domainless FX. To test this hypothesis, we mutated both residues Lys165 and Lys166 of TF to Ala, Glu, or Gln and examined the ability of these double mutants to support FVIIa-mediated activation of FX, Gla domainless FX, and factor IX (FIX). Each TF mutant was equivalent to wild-type TF in both FVIIa binding and promotion of FVIIa amidolytic activity. However, all three mutants were markedly deficient in supporting FIX and FX activation, with FX activation rates decreased more than FIX activation rates. In both reactions, the TF mutants exhibited different extents of activity: Gln165-Gln166 > Ala165-Ala166 > Glu165-Glu166. In sharp contrast, all three TF mutants were equivalent to wild-type TF in supporting activation of Gla domainless FX by FVIIa. Interestingly, the deficiency of the mutants in FX activation was less pronounced when Gla domainless FVIIa was used in place of native FVIIa. Together, these findings suggest that TF residues Lys165 and Lys166 contribute to a binding site for the Gla domain of FX (and perhaps other substrates) and that this interaction may be facilitated by the presence of the Gla domain of FVIIa.
A high conductivity oxide–sulfide composite lithium superionic conductor (2014)

A composite of LLZO and LPS inherits the excellent processability of the sulfide and exceeds the conductivity of parent components.
Synthesis of (5′S)-5′-C-Alkyl-2′-deoxynucleosides (2001)

We describe the synthesis of (5′S)-5′-C-butylthymidine (5a), of the (5′S)-5′-C-butyl- and the (5′S)-5′-C-isopentyl derivatives 16a and 16b of 2′-deoxy-5-methylcytidine, as well as of the corresponding cyanoethyl phosphoramidites 9a, b and 14a, b, respectively. Starting from thymidin-5′-al 1, the alkyl chain at C(5′) is introduced via Wittig chemistry to selectively yield the (Z)-olefin derivatives 3a and 3b (Scheme 2). The secondary OH function at C(5′) is then introduced by epoxidation followed by regioselective reduction of the epoxy derivatives 4a and 4b with diisobutylaluminium hydride. In the latter step, a kinetic resolution of the diastereoisomer mixture 4a and 4b occurs, yielding the alkylated nucleoside 2a and 2b, respectively, with (5′S)-configuration in high diastereoisomer purity (de=94%). The corresponding 2′-deoxy-5-methylcytidine derivatives are obtained from the protected 5′-alkylated thymidine derivatives 7a and 7b via known base interconversion processes in excellent yields (Scheme 3). Application of the same strategy to the purine nucleoside 2′-deoxyadenine to obtain 5′-C-butyl-2′-deoxyadenosine 25 proved to be difficult due to the sensitivity of the purine base to hydride-based reducing agents (Scheme 4).
Probabilistic spatial context models for scene content understanding (2003)

Scene content understanding facilitates a large number of applications, ranging from content-based image retrieval to other multimedia applications. Material detection refers to the problem of identifying key semantic material types (such as sky, grass, foliage, water, and snow in images). In this paper, we present a holistic approach to determining scene content, based on a set of individual material detection algorithms, as well as probabilistic spatial context models. A major limitation of individual material detectors is the significant number of misclassifications that occur because of the similarities in color and texture characteristics of various material types. We have developed a spatial context-aware material detection system that reduces misclassification by constraining the beliefs to conform to the probabilistic spatial context models. Experimental results show that the accuracy of materials detection is improved by 13% using the spatial context models over the individual material detectors themselves.
Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity (1999)

The protective effects of the hormones androstenediol (androstene-3beta, 17beta,-diol; AED) and dehydroepiandrosterone (5-androsten-3beta-ol-17-one; DHEA) on the pathophysiology of two lethal bacterial infections and endotoxin shock were examined. The infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginosa). Both hormones protected mice from the lethal bacterial infections and from lipopolysaccharide (LPS) challenge. Treatment of animals lethally infected with P. aeruginosa with DHEA resulted in a 43% protection whereas treatment with AED gave a 67% protection. Both hormones also protected completely animals infected with an LD50 dose of E. faecalis. Similarly, the 88% mortality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with DHEA and AED, respectively. The protective influences of both steroids were shown not to be directly antibacterial, but primarily an indirect antitoxin reaction. DHEA appears to mediate its protective effect by a mechanism that blocks the toxin-induced production of pathophysiological levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1. AED usually had greater protective effects than DHEA; however, the AED effect was independent of TNF-alpha suppression, both in vivo and in vitro. The data suggest that both DHEA and AED may have a role in the neuro-endocrine regulation of antibacterial immune resistance.
Formal intent based Flight Management System design for unmanned aerial vehicles (2014)

This paper presents a formal intent based Flight Management System (FMS) hardware and functional structure utilising multi-level autonomy modes. The novel advanced capabilities added to the UAV autopilots are envisioned to meet the requirements of the future flight operations of the UAVs integrated into national airspace. The proposed FMS structure integrates new functionalities such as a) formal intent based information exchange and collaborative tactical planning utilising air-to-air and air-to-ground data links and, b) decentralised immediate sense-and-avoid. The collaborative nominal operation mode enables the ground operator to build “shared intelligence” with the UAV through the intent sharing. In this mode, the intent sharing process benefits from the advantages of formal intent languages at different levels of abstraction and data-links. The air-to-ground data link allows the ground operator to update/modify/re-plan the flight intent (FI) of the UAV(s) in any phase of the operation according to evolving situations through ground station. The air-to-air intent sharing also continues between the surrounding aircraft through the aircraft intent (AI) (“machine-to-machine” level) communication which makes unmanned systems to be visible. The sense-and-avoid mode, the FMS recursively computes and observes the probabilities of potential immediate collisions with the other aircraft and terrain. Whenever the immediate response needs, the FMS executes the generated 3D avoidance maneuver. For technology demonstration purposes, an experimental FMS hardware has been deployed in a quadrotor UAV, and a ground operator station with GUI has been designed enabling envisioned operational experiments.
Real-Time PCR and Melting Curve Analysis for Reliable and Rapid Detection of SHV Extended-Spectrum β-Lactamases (2001)

Extended-spectrum beta-lactamases (ESBLs), e.g., ESBLs of the TEM or SHV type, compromise the efficacies of expanded-spectrum cephalosporins. An SHV non-ESBL that hydrolyzes only narrow-spectrum cephalosporins can be converted into an SHV ESBL through substitutions at three amino acid positions, 179, 238, or 238--240. In order to improve detection of SHV ESBLs, a novel method, based on real-time PCR monitored with fluorescently labeled hybridization probes and followed by melting curve analysis, was developed. It is able to (i) detect bla(SHV) genes with high degrees of sensitivity and specificity, (ii) discriminate between bla(SHV non-ESBL) and bla(SHV ESBL), and (iii) categorize the SHV ESBL producers into three phenotypically relevant subgroups. This method, termed the SHV melting curve mutation detection method, represents a powerful tool for epidemiological studies with SHV ESBLs. It even has the potential to be used in the diagnostic microbiology laboratory, because up to 32 clinical isolates can be processed in less than 1 h by starting with just a few bacterial colonies.