gebhart/patrepeval huggingface dataset:
Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist (2005)

Promising recent developments in the therapeutic value of neuropeptide antagonists have generated renewed importance in understanding the functional role of neuropeptides in nociception and inflammation. To explore this relationship we examined behavioral changes and primary afferent neuronal plasticity following deep tissue inflammation. One hour following craniofacial muscle inflammation ipsilateral as well as contralateral head withdrawal thresholds and ipsi- and contralateral hindpaw withdrawal thresholds were lowered and remained reduced for 28 days. Elevated levels of calcitonin gene-related peptide (CGRP) within the trigeminal ganglion temporally correlated with this mechanical allodynia. Inflammation also induced an increase in the number of CGRP and substance P (SP)-immunopositive trigeminal ganglion neurons innervating inflamed muscle but did not evoke a shift in the size distribution of peptidergic muscle afferent neurons. Trigeminal proprioceptive muscle afferent neurons situated within the brainstem in the mesencephalic trigeminal nucleus did not express CGRP or SP prior to or following inflammation. Intravenous administration of CGRP receptor antagonist (8-37) two minutes prior to adjuvant injection blocked plasma extravasation and abolished both head and hindlimb mechanical allodynia. Local injection of CGRP antagonist directly into the masseter muscle prior to CFA produced similar, but less pronounced, effects. These findings indicate that unilateral craniofacial muscle inflammation produces mechanical allodynia at distant sites and upregulates CGRP and SP in primary afferent neurons innervating deep tissues. These data further implicate CGRP and SP in deep tissue nociceptive mechanisms and suggest that peptide antagonists may have therapeutic potential for musculoskeletal pain.
Unified derivation of phase-field models for alloy solidification from a grand-potential functional (2011)

In the literature, two quite different phase-field formulations for the problem of alloy solidification can be found. In the first, the material in the diffuse interfaces is assumed to be in an intermediate state between solid and liquid, with a unique local composition. In the second, the interface is seen as a mixture of two phases that each retain their macroscopic properties, and a separate concentration field for each phase is introduced. It is shown here that both types of models can be obtained by the standard variational procedure if a grand-potential functional is used as a starting point instead of a free energy functional. The dynamical variable is then the chemical potential instead of the composition. In this framework, a complete analogy with phase-field models for the solidification of a pure substance can be established. This analogy is then exploited to formulate quantitative phase-field models for alloys with arbitrary phase diagrams. The precision of the method is illustrated by numerical simulations with varying interface thickness.
Intracellular expression of a single-chain antibody directed to the EGFR leads to growth inhibition of tumor cells. (1996)

A gene encoding a single-chain antibody (scFv) which specifically binds the epidermal growth factor receptor (EGFR) has been constructed from hybridoma cells producing the R1 monoclonal antibody. The gene, designated scFv-R1R, was introduced into EGFR transformed NIH3T3 cells via retroviral infection. scFv-R1R was directed to the lumen of the endoplasmic reticulum (ER) where it bound the extracellular domain of the receptor inhibiting its appearance on the plasma membrane. In these cells, EGF induced tyrosine phosphorylation of the EGFR and several substrates was greatly reduced. Furthermore, intracellular retention of EGFR caused a partial inhibition in the transformed growth of the cells. Intracellular expression of receptor tyrosine kinase directed scFvs is a novel approach for affecting tumor cell growth. We have recently shown that scFv-5R directed to ErbB2, another member of the ErbB family, blocks the anchorage independent growth of ErbB2 transformed cells. In order to examine the effects of scFv-R1R and scFv-5R on the long-term growth of tumor cells overexpressing either EGFR or ErbB2, retroviruses encoding the two scFvs were used to infect various human tumor cell lines. Intracellular expression of the scFvs resulted in a marked inhibition of stable colony formation in some of the cell lines. In general, inhibition was observed when overexpressed receptor was targeted. However, in some cases expression of both scFvs was incompatible with long term cell growth suggesting that heterodimers of ErbB2 and EGFR are essential for the growth of some human tumor cell lines.
A Hydrophobic Domain of Ca -modulating Cyclophilin Ligand Modulates Calcium Influx Signaling in T Lymphocytes (1996)

Ca2+-modulating cyclophilin ligand (CAML) was originally described as a cyclophilin B-binding protein whose overexpression in T cells causes a rise in intracellular calcium, thus activating transcription factors responsible for the early immune response. As reported here, structure-function analysis of the CAML gene in Jurkat T cells indicates that two of CAML's putative membrane-spanning domains are necessary and sufficient for the modulation of intracellular calcium. We propose that the hydrophobic C-terminal tail of CAML forms its effector domain, thus implicating the N-terminal hydrophilic domain in a regulatory role. These findings define a novel protein motif that functions in intracellular calcium signaling.
In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA (2001)

Nasal administration of plasmid DNA is emerging as a new route of delivery for therapeutic genes and DNA vaccines. To improve the intranasal absorption of plasmid DNA, we designed delivery systems composed of in situ gelling and mucoadhesive polymers. Poloxamers (Pol) were used to provide in situ gelling property. Polycarbophil (PC) or polyethylene oxide (PEO) was used as mucoadhesive polymers. The gelation temperatures of the formulations slightly decreased by the mucoadhesive polymers, but not by plasmid DNA. The in vitro release of plasmid DNA from the gels followed Fickian diffusion. The absorption of plasmid DNA varied with the contents and type of mucoadhesive polymers. Of vehicles, Pol/PC 0.2% showed the highest absorption with an area under the curve value 11-fold higher than saline, the conventional vehicle. The nasal retention of plasmid DNA was highly prolonged by mucoadhesive polymers. At 3 h postdose, the nasal tissue levels of plasmid DNA given in Pol/PC and Pol/PEO 0.8% were 10- and 40-fold higher relative to saline. The histopathology of nasal tissues was not altered after repeated dosing over 2 weeks. The mRNA expression of plasmid DNA delivered by Pol or Pol/PEO 0.4% was observed in the nasal tissues. These results indicate that the nasal absorption of plasmid DNA can be effectively and safely enhanced by using in situ gelling and mucoadhesive polymer-based vehicles.
Influence of buffer-layer surface morphology on the self-organized growth of InAs on InP(001) nanostructures (2000)

We have studied the influence of InP buffer-layer morphology in the formation of InAs nanostructures grown on InP(001) substrates by solid-source molecular-beam epitaxy. Our results demonstrate that when InP buffer layers are grown by atomic-layer molecular-beam epitaxy, InAs quantum dot-like structures are formed, whereas InP buffer layers grown by MBE produce quantum-wire-like structures. The optical properties of these corrugated structures make them potential candidates for their use in light-emitting devices at 1.55 μm.
Efficient Enantioselective Reduction of Ketones with Daucus carota Root (2002)

A novel and efficient reduction of various prochiral ketones such as acetopehones, alpha-azido aryl ketones, beta-ketoesters, and aliphatic acyclic and cyclic ketones to the corresponding optically acive secondary alcohols with moderate to excellent chemical yield was achieved by using Daucus carota, root plant cells under extremely mild and environmentally benign conditions in aqueous medium, has been described. Many of these optically active alcohols are the potential chiral building blocks for the synthesis of pharmaceutically important molecules and asymmetric chiral ligands. Hence, this biocatalytic approach is found to be the most suitable for the preparation of a wide range of chiral alcohols and gave inspiration for the development of a new biotechnological process.
The FBXO4 Tumor Suppressor Functions as a Barrier to BrafV600E-Dependent Metastatic Melanoma (2013)

Cyclin D1-cyclin-dependent kinase 4/6 (CDK4/6) dysregulation is a major contributor to melanomagenesis. Clinical evidence has revealed that p16(INK4A), an allosteric inhibitor of CDK4/6, is inactivated in over half of human melanomas, and numerous animal models have demonstrated that p16(INK4A) deletion promotes melanoma. FBXO4, a specificity factor for the E3 ligase that directs timely cyclin D1 proteolysis, has not been studied in melanoma. We demonstrate that Fbxo4 deficiency induces Braf-driven melanoma and that this phenotype depends on cyclin D1 accumulation in mice, underscoring the importance of this ubiquitin ligase in tumor suppression. Furthermore, we have identified a substrate-binding mutation, FBXO4 I377M, that selectively disrupts cyclin D1 degradation while preserving proteolysis of the other known FBXO4 substrate, TRF1. The I377M mutation and Fbxo4 deficiency result in nuclear accumulation of cyclin D1, a key transforming neoplastic event. Collectively, these data provide evidence that FBXO4 dysfunction, as a mechanism for cyclin D1 overexpression, is a contributor to human malignancy.
SECRETION AND ABSORPTION BY COLONIC CRYPTS (2004)

The intestines play an important role in the absorption and secretion of nutrients. The colon is the final area for recapturing electrolytes and water prior to excretion, and in order to maintain this electrolyte homeostasis, a complex interaction between secretory and absorptive processes is necessary. Until recently it was thought that secretion and absorption were two distinct processes associated with either crypts or surface cells, respectively. Recently it was demonstrated that both the surface and crypt cells can perform secretory and absorptive functions and that, in fact, these functions can be going on simultaneously. This issue is important in the complexities associated with secretory diarrhea and also in attempting to develop treatment strategies for intestinal disorders. Here, we update the model of colonic secretion and absorption, discuss new issues of transporter activation, and identify some important new receptor pathways that are important modulators of the secretory and absorptive functions of the colon.
Activation of the Aryl Hydrocarbon Receptor by Structurally Diverse Exogenous and Endogenous Chemicals (2003)

The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of several chemical/ligand-dependent intracellular receptors that can stimulate gene transcription in response to xenobiotics. The ability of the AhR to bind and be activated by a range of structurally divergent chemicals suggests that the AhR contains a rather promiscuous ligand binding site. In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified. In this review, we describe evidence for the structural promiscuity of AhR ligand binding and discuss the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands.
The selenocysteine-inserting opal suppressor serine tRNA fromE.coliis highly unusual in structure and modification (1989)

Selenocysteine is cotranslationally incorporated into selenoproteins in a unique pathway involving tRNA mediated suppression of a UGA nonsense codon (1-3). The DNA sequence of the gene for this suppressor tRNA from Escherichia coli predicts unusual features of the gene product (4). We determined the sequence of this serine tRNA (tRNA(UCASer]. It is the longest tRNA (95 nt) known to date with an acceptor stem of 8 base pairs and lacks some of the 'invariant' nucleotides found in other tRNAs. It is the first E. coli tRNA that contains the hypermodified nucleotide i6A, adjacent to the UGA-recognizing anticodon UCA. The implications of the unusual structure and modification of this tRNA on recognition by seryl-tRNA synthetase, by tRNA modifying enzymes, and on codon recognition are discussed.
Development and Evaluation of a Vaccine for Human Immunodeficiency Virus (HIV) Infection (1989)

The development of a safe and effective vaccine for infection with human immunodeficiency virus (HIV) is complicated by several unique scientific, logistic, and ethical issues. These issues include a lack of understanding of protective immunity to HIV and disease development, the absence of an adequate and convenient animal model for studying HIV infection, and difficulties in phase III evaluation of candidate vaccines. Because HIV can be transmitted as either a cell-free or cell-associated virus, a protective immune response against HIV infection will likely require both humoral and cell-mediated immunity. A neutralizing antibody against HIV and an antibody involved in antibody-dependent cellular cytotoxicity have been shown in HIV-infected persons, but their precise relation to protection is unclear. Cytotoxic lymphocytes from HIV-infected persons have been shown to lyse target cells expressing HIV or its proteins. Cloned T cells have been developed that manifest HIV-specific, major histocompatibility-complex class I-restricted cytotoxic capabilities that are broadly specific. Thus far, all attempts to protect chimpanzees, currently the only suitable animal model, from HIV infection have failed. Ongoing vaccine studies in humans include phase I trials of recombinant proteins of the HIV envelope in uninfected persons as well as the administration of whole killed virus to persons already infected with HIV. Rapid progress is being made in the development of new animal models for HIV infection. The establishment of alternative animal models, both primate and small animal models, will greatly facilitate the development of a vaccine for HIV infection.
Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress (2010)

The mucus layer coating the gastrointestinal tract is the front line of innate host defense, largely because of the secretory products of intestinal goblet cells. Goblet cells synthesize secretory mucin glycoproteins (MUC2) and bioactive molecules such as epithelial membrane-bound mucins (MUC1, MUC3, MUC17), trefoil factor peptides (TFF), resistin-like molecule beta (RELMbeta), and Fc-gamma binding protein (Fcgbp). The MUC2 mucin protein forms trimers by disulfide bonding in cysteine-rich amino terminal von Willebrand factor (vWF) domains, coupled with crosslinking provided by TFF and Fcgbp proteins with MUC2 vWF domains, resulting in a highly viscous extracellular layer. Colonization by commensal intestinal microbiota is limited to an outer "loose" mucus layer, and interacts with the diverse oligosaccharides of mucin glycoproteins, whereas an "inner" adherent mucus layer is largely devoid of bacteria. Defective mucus layers resulting from lack of MUC2 mucin, mutated Muc2 mucin vWF domains, or from deletion of core mucin glycosyltransferase enzymes in mice result in increased bacterial adhesion to the surface epithelium, increased intestinal permeability, and enhanced susceptibility to colitis caused by dextran sodium sulfate. Changes in mucin gene expression and mucin glycan structures occur in cancers of the intestine, contributing to diverse biologic properties involved in the development and progression of cancer. Further research is needed on identification and functional significance of various components of mucus layers and the complex interactions among mucus layers, microbiota, epithelial cells, and the underlying innate and adaptive immunity. Further elucidation of the regulatory mechanisms involved in mucin changes in cancer and inflammation may lead to the development of novel therapeutic approaches.
Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. (1990)

The Saccharomyces cerevisiae CDC42 gene product is involved in the morphogenetic events of the cell division cycle; temperature-sensitive cdc42 mutants are unable to form buds and display delocalized cell-surface deposition at the restrictive temperature (Adams, A. E. M., D. I. Johnson, R. M. Longnecker, B. F. Sloat, and J. R. Pringle. 1990. J. Cell Biol. 111:131-142). To begin a molecular analysis of CDC42 function, we have isolated the CDC42 gene from a yeast genomic DNA library. The use of the cloned DNA to create a deletion of CDC42 confirmed that the gene is essential. Overexpression of CDC42 under control of the GAL10 promoter was not grossly deleterious to cell growth but did perturb the normal pattern of selection of budding sites. Determination of the DNA and predicted amino acid sequences of CDC42 revealed a high degree of similarity in amino acid sequence to the ras and rho (Madaule, P., R. Axel, and A. M. Myers. 1987. Proc. Natl. Acad. Sci. 84:779-783) families of gene products. The similarities to ras proteins (approximately 40% identical or related amino acids overall) were most pronounced in the regions that have been implicated in GTP binding and hydrolysis and in the COOH-terminal modifications leading to membrane association, suggesting that CDC42 function also involves these biochemical properties. The similarities to the rho proteins (approximately 60% identical or related amino acids overall) were more widely distributed through the coding region, suggesting more extensive similarities in as yet undefined biochemical properties and functions.
JSketch: sketching for Java (2015)

Sketch-based synthesis, epitomized by the Sketch tool, lets developers synthesize software starting from a partial program, also called a sketch or template. This paper presents JSketch, a tool that brings sketch-based synthesis to Java. JSketch's input is a partial Java program that may include holes, which are unknown constants, expression generators, which range over sets of expressions, and class generators, which are partial classes. JSketch then translates the synthesis problem into a Sketch problem; this translation is complex because Sketch is not object-oriented. Finally, JSketch synthesizes an executable Java program by interpreting the output of Sketch.
Cloning of an aquaporin homologue present in water channel containing endosomes of toad urinary bladder (1996)

Regulation of total body water balance in amphibians by antidiuretic hormone (ADH) contributed to their successful colonization of terrestrial habitats approximately 200-300 million years ago. In the mammalian kidney, ADH modulates epithelial cell apical membrane water permeability (Pf) by fusion and retrieval of cytoplasmic vesicles containing water channel proteins called aquaporins (AQPs). To determine the role of AQPs in ADH-elicited Pf in amphibians, we have identified and characterized a unique AQP from Bufo marinus called AQP toad bladder (AQP-TB). AQP-TB possesses many structural features common to other AQPs, AQP-TB is expressed abundantly in ADH-responsive tissues, including toad urinary bladder and skin as well as lung, skeletal muscle, kidney, and brain. In a manner identical to that reported for the mammalian ADH-elicited water channel AQP2, AQP-TB expression is increased significantly by intervals of dehydration or chronic ADH stimulation. However, expression of AQP-TB protein in Xenopus laevis oocytes does not significantly increase oocyte Pf. The lack of expression of functional AQP-TB water channels in oocytes may result from intracellular sequestration of AQP-TB due to the presence of a YXRF sequence motif present in its carboxyterminal domain.
Stoichiometry, Kinetic and Binding Analysis of the Interaction between Epidermal Growth Factor (EGF) and the Extracellular Domain of the EGF Receptor (2000)

The kinetics, binding equilibria and stoichiometry of the interaction between epidermal growth factor and the soluble extracellular domain of the epidermal growth factor receptor (sEGFR), produced in CHO cells using a bioreactor, have been studied by three methods: analytical ultracentrifugation, biosensor analysis using surface plasmon resonance detection (BIAcore 2000) and fluorescence anisotropy. These studies were performed with an sEGFR preparation purified in the absence of detergent using a mild two step chromatographic procedure employing anion exchange and size exclusion HPLC. The fluorescence anisotropy and analytical ultracentrifugation data indicated a 1:1 molar binding ratio between EGF and the sEGFR. Analytical ultracentrifugation further indicated that the complex comprised 2EGF:2sEGFR, consistent with the model proposed recently by Lemmon et al. (1997). Global analysis of the BIAcore binding data showed that a simple Langmuirian interaction does not adequately describe the EGF:sEGFR interaction and that more complex interaction mechanisms are operative. Furthermore, analysis of solution binding data using either fluorescence anisotropy or the biosensor, to determine directly the concentration of free sEGFR in solution competition experiments, yielded Scatchard plots which were biphasic and Hill coefficients of less than unity. Taken together our data indicate that in solution there are two sEGFR populations; one which binds EGF with a KD of 2-20 nM and the other with a KD of 400-550 nM.
Isolation and characterization of a Streptococcus pyogenes protein that binds to basal laminae of human cardiac muscle (1993)

A 9-kDa glycosaminoglycan-binding protein (GAG-BP) was isolated from Streptococcus pyogenes and purified to homogeneity by affinity chromatography on heparin-agarose. The protein selectively bound to the basal laminae of human cardiac muscle and had an apparent dissociation constant of 2.5 x 10(-7) M. Chemical analyses indicated that the GAG-BP was rich in alanine, lysine, and arginine (pI 9.5) and devoid of tyrosine, methionine, histidine, and half-cystine. There were no detectable carbohydrate or phosphate substituents. The amino acid sequence of the N terminus of GAG-BP showed homology with those of histone-like DNA-binding proteins of several other bacteria. Circular dichroism spectroscopy indicated that the protein was made up of 50% beta-sheet and 50% beta-turn and random coil in aqueous solution; however, when the protein complexed with heparin, it adopted a more ordered structure containing 25% alpha-helix, 50% beta-sheet, and 25% beta-turn and random coil. The GAG-BP cross-reacted serologically with a component of similar size in extracts of other group A streptococci and was present in the culture medium during late logarithmic growth.