UK PubMed Central (United Kingdom)

The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)₂ or...Full Text Available

UK PubMed Central (United Kingdom)

The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both...Full Text Available

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To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer ...

UK PubMed Central (United Kingdom)

Background:Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.Patients...Full Text Available

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available

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No abstract prepared.

UK PubMed Central (United Kingdom)

In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two...Full Text Available

UK PubMed Central (United Kingdom)

The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate...Full Text Available

UK PubMed Central (United Kingdom)

SUMMARYTestosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior...Full Text Available

UK PubMed Central (United Kingdom)

The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

UK PubMed Central (United Kingdom)

Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available

UK PubMed Central (United Kingdom)

Osteoblasts are the primary cells responsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available

UK PubMed Central (United Kingdom)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available

Science.gov (United States)

Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. ...

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A study was made of the kinetics of L-(/sup 3/H)quinuclidinyl benzilate binding with membrane-bound muscarine cholinoreceptors from the rat brain. Determination was made of the rate constants of this process, and constants as a function of ligand concentration was investigated, indicating that there is a complex mechanism of interaction of antagonists with muscarine receptor. With up to 3.5 nM concentrations of L-(/sup 3/H)quinuclidinyl benzilate, the binding reaction occurs in two stages: rapid equilibrated binding is followed by a slow process of conformational isomerization of the receptor-ligand complex. At higher ligand concentrations, there is additional drastic increase in constant of rate of ligand binding a new plateau is reached. Such dependence of rate constant on ligand concentration is indicative of the cooperative nature of interaction between antagonists and muscarine ...

UK PubMed Central (United Kingdom)

Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor β superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available

Science.gov (United States)

HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, ...

UK PubMed Central (United Kingdom)

α₁-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available

UK PubMed Central (United Kingdom)

Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A₁R, A_2AR, A_2BR, and A₃R)....Full Text Available

UK PubMed Central (United Kingdom)

In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available

UK PubMed Central (United Kingdom)

Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions...Full Text Available

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Incorporation of /sup 32/P from (gamma-32P)ATP into tyrosine residues of the insulin-like growth factor (IGF)-II receptor was observed in a Triton X-100-insoluble fraction of rat adipocyte plasma membranes. IGF-II receptor phosphorylation proceeded to a stoichiometry of approximately 0.5 mol of phosphate/IGF-II binding site after 10 min of incubation at 4 degrees C. A Km for ATP of 6 microM was calculated for this phosphorylation reaction. Addition of IGF-II caused an approximately 2-fold increase in tyrosine phosphorylation of the IGF-II receptor in this preparation. In contrast, phosphorylation of angiotensin II by the Triton X-100 washed membranes was not stimulated by IGF-II. Incubation of purified receptor immobilized on IGF-II agarose or of receptor-enriched low density microsomal membranes with (gamma-32P)ATP did not result in appreciable incorporation of ...

UK PubMed Central (United Kingdom)

The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available

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Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl`s ...

UK PubMed Central (United Kingdom)

BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available

UK PubMed Central (United Kingdom)

Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available

UK PubMed Central (United Kingdom)

Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available

UK PubMed Central (United Kingdom)

Mechanisms regulating sexual differentiation of the zebra finch song system appear to include both genetic and hormonal factors. Sorting Nexin 2 (SNX2), which is involved in trafficking proteins...Full Text Available

UK PubMed Central (United Kingdom)

Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter,...Full Text Available

UK PubMed Central (United Kingdom)

Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulate cell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling....Full Text Available

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Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in ...

International Nuclear Information System (INIS)

The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) ...

British Library Electronic Table of Contents (United Kingdom)

Background: Thyroid-stimulating autoantibodies (TSAb) bind to the thyrotropin receptor (TSHR) extracellular domain, or ectodomain (ECD), comprising a leucine-rich repeat domain (LRD) linked by a hinge region to the transmembrane domain (TMD). The LRD (residues 22???260; signal peptide 1???21) contains two disulfide-bonded loops at its N-terminus. In the crystal structure of the isolated LRD complexed with human TSAb monoclonal antibody (mAb) M22, N-terminal disulfide loop 1 (residues 22???30) could not be determined because of crystal disorder. Nevertheless, present crystal structure data are interpreted to exclude a role for the LRD N-terminal disulfide loops in the TSAb epitope(s), contradicting prior functional evidence of a role for these loops in TSAb function. Materials and Methods: ...

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Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal ...

Science.gov (United States)

Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf promoters to drive the ...

UK PubMed Central (United Kingdom)

Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.

UK PubMed Central (United Kingdom)

The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction...Full Text Available

International Nuclear Information System (INIS)

Targeted studies completed include the evaluation of tritiated N-0437, evaluation of "3"5S-cysteamine, evaluation of "1"8F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic ...

British Library Electronic Table of Contents (United Kingdom)

Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...

British Library Electronic Table of Contents (United Kingdom)

Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater struct...

British Library Electronic Table of Contents (United Kingdom)

Endogenous opioid peptides (EOP) are molecules affecting many biological functions influencing productive and reproductive performance. They increase in stress conditions and interact with specific opioidergic receptors (OR): delta, kappa and mu. Several studies in other animal species suggest that they can also affect sperm cell motility. In fish the ionic external environment modulates the increase of intracellular calcium ion that is required to activate sperm motility after spawning. In mammals OR are functionally associated to calcium channels and in fishes calcium is highly required for fish sperm activation. In this study the presence of OR on spermatozoa of two Perciform fish, the sharpsnout seabream (Diplodus puntazzo, family Sparidae) and the European sea bass (Dicentrarchus labr...

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The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.

International Nuclear Information System (INIS)

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A ...

British Library Electronic Table of Contents (United Kingdom)

Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...

International Nuclear Information System (INIS)

We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. ...

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Investigations of cadmium toxicity to microorganisms are now more concerned with the interactions of cadmium with different environmental factors and other metals. The interactions are complex and have not been thoroughly studied yet. Metal interactions may assume the form of synergism characterized by increase in toxicity, but also of antagonism in which one metal reduces the toxicity of another. Apart from cadmium interactions with such toxic metals as mercury and lead, interactions of cadmium with the essential trace elements seem to be very interesting because it has been assumed that algal cells take up cadmium by the system transporting these elements. A previous study showed that cadmium transport into Stichococcus bacillaris cells was inhibited by Mn/sup 2 +/ ions. Thus, it can be supported that there exist some possibilities of using those ions ...

UK PubMed Central (United Kingdom)

Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic...Full Text Available

UK PubMed Central (United Kingdom)

AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the...Full Text Available

UK PubMed Central (United Kingdom)

CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available

UK PubMed Central (United Kingdom)

Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable...Full Text Available

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A micro-mechanistic understanding of bone fracture thatencompasses how cracks interact with the underlying microstructure anddefines their local failure mode is lacking, despite extensive research nthe response of bone to a variety of factors like aging, loading, and/ordisease.

UK PubMed Central (United Kingdom)

Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate...Full Text Available

Science.gov (United States)

We discuss elastic electron-deuteron (ed) scattering beyond the Born approximation. The reaction amplitude contains six generalized form factors, but only three linearly independent combinations of them (generalized charge, quadrupole, and magnetic form factors) contribute to the reaction cross section in second-order perturbation theory. We examine the two-photon exchange and find that it includes two types of diagrams, where two virtual photons are interacting with the same nucleon and where the photons are interacting with different nucleons. It is shown that the two-photon-exchange amplitude is strongly connected with the deuteron wave function at short distances.

UK PubMed Central (United Kingdom)

Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat...Full Text Available

Science.gov (United States)

PMID:19469866

Science.gov (United States)

Acute Asthma

International Nuclear Information System (INIS)

The interaction of the herbicide paraquat dichloride (P Q, substrate) with p-tert-butylcalix arenas (L, receptor) was investigated in both the solution and solid states. The isolated paraquat calixarene complexes were characterised by UV-visible, 1H NMR, ESI-Ms, Luminescence and IR spectroscopies and elemental analysis. The stoichiometry of complexes 1 and 2 was 1:1 (1 herbicide: 1 calixarene) and both revealed a biexponential luminescence decay with lifetimes depending on the size and the conformational particularity of the calixarenes. Molecular modelling suggested that both calixarenes interact with the herbicide through cation-? interaction. P Q in included in the p-tert butylcalix a rene cavity, a situation favoured by its pinched conformation in polar solvent while it is partially included in the p-tert butylcalix a rene cavity because of its in-out cone conformation. The theoretical results, in ...

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The LAHET code system calculations and experimental results for proton interactions with an energy <50 MeV are compared. For these energies, the theories behind the LAHET models are not applicable. Three quantities compared are (a) the magnitude of the neutron yield generated through proton interactions, (b) the energy and angular distributions of the resultant neutrons, and (c) the residual nuclei produced by proton interactions (spallation products). The comparisons are for protons incident on iron and copper, except in the case of the energy and angular distributions, which are calculated only for iron. The neutron yields predicted by LAHET agree with published measurements to within 50% for both materials. For iron, the predicted energy and angular distributions agree to within a factor of 3. Finally, the predicted spallation product yields of both materials agree with measurements to within a ...

UK PubMed Central (United Kingdom)

Arf GTPases control vesicle formation from different intracellular membranes and are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their conserved catalytic domains, known...Full Text Available

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The decays of charmed mesons into two body nonleptonic final states are investigated. Weak interaction amplitudes of interest in these decays are extracted from lattice four-point correlation functions using a effective weak Hamiltonian including effects to order G{sub f} in the weak interactions yet containing effects to all orders in the strong interactions. The lattice calculation allows a quantitative examination of non-spectator processes in charm decays helping to elucidate the role of effects such as color coherence, final state interactions and the importance of the so called weak annihilation process. For D {yields} K{pi}, we find that the non-spectator weak annihilation diagram is not small, and we interpret this as evidence for large final state interactions. Moreover, there is indications of a resonance in the isospin {1/2} channel to which the weak annihilation process ...

Science.gov (United States)

The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as ...

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Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of (/sup 125/I)EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM (/sup 125/I)EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium ...

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Gamma-aminobutyric acid type A receptor-associated protein (GABARAP) belongs to a family of small ubiquitin-like adaptor proteins implicated in intracellular vesicle trafficking and autophagy. We have used diffusion-ordered nuclear magnetic resonance spectroscopy to study the temperature and concentration dependence of the diffusion properties of GABARAP. Our data suggest the presence of distinct conformational states and provide support for self-association of GABARAP molecules. Assuming a monomer-dimer equilibrium, a temperature-dependent dissociation constant could be derived. Based on a temperature series of {sup 1}H{sup 15}N heteronuclear single quantum coherence nuclear magnetic resonance spectra, we propose residues potentially involved in GABARAP self-interaction. The possible biological significance of these observations is discussed with respect to alternative scenarios of oligomerization.

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In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of the study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input ...

Science.gov (United States)

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at ...

International Nuclear Information System (INIS)

The properties of negative-ion beams are very important for designing negative-ion apparatus and applications of negative-ion beams, especially, electron detachment cross-sections at the interaction between negative-ion beams and gas particles in the transport system, and secondary-electron emission factors when negative ions are incident on solid surfaces. These properties of negative-ion beams were investigated experimentally as a function of the ion energy under 50 keV. The single electron detachment cross-sections are almost constant in the other of 10"-"1"5 cm"2 in this energy range, but double electron detachment cross-sections increase in proportion to the ion velocity and much smaller than the single one. As for the secondary-electron emission factor, the emission factors for negative-ion beam are found to be larger by 1 than those for positive-ion beams. (author).

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The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.

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Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucl2048 These connections are made via membrane-bound ...

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Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen ...

International Nuclear Information System (INIS)

Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.

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This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Host-microorganism interactions in the intestinal tract are complex, and little is known about specific nonpathogenic microbial factors triggering host responses in the gut. In this study, mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using an in situ pig Small Intestinal Segment Perfusion model. The effects of L. plantarum 299v wild-type strain were compared with those of two corresponding mutant strains either lacking the gene encoding for the mannose-specific adhesin (msa) or sortase (srtA; responsible for anchoring of cell surface proteins like Msa to the cell wall). A slight enrichment of the wild-type strain associated with the intestinal surface could be observed after 8 h of perfusion when a mixture of wild-type and...

UK PubMed Central (United Kingdom)

BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available

UK PubMed Central (United Kingdom)

Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article...Full Text Available

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1. The effects of stimulation of atrial receptors on hypothalamic neurosecretory cells were investigated in anaesthetized dogs and cats. Atrial receptors were activated by stretching the left and the...Full Text Available

UK PubMed Central (United Kingdom)

A specific immunoglobulin, the receptor antibody, can be found in most patients with myasthenia gravis. In order to study the kinetic properties of this antibody, serial determinations of receptor antibody,...Full Text Available

UK PubMed Central (United Kingdom)

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen...Full Text Available

Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization ...

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The report addresses the application of reverse osmosis to the treatment of radioactive liquid waste, focusing on the effects of non-radioactive cations and anions, existing in radioactive waste, on the removal of radioactive nuclides. The bivalent cations are generally about ten times as high in decontamination factor as monovalent ones. In the case of anions, the factor of SO{sub 4}{sup 2-} is about ten times that of Cl{sup -} while that of NO{sub 3}{sup -} is somewhat smaller than that of Cl{sup -}. During permeation through membrane, anions tend to accompany cations, and the decontamination factor of accompanying ions is found to increase with that of the paring ions. These results indicate that if one can select components that will remain in the liquid waste, one should consider their effects on the efficiency of its treatment. Furthermore, the interaction between two anions or between two cations ...

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Histamine and the histamine receptors are important regulators of a plethora of biological processes, including immediate hypersensitivity reactions and acid secretion in the stomach. In these...Full Text Available

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CD44, a transmembrane receptor for hyaluronic acid, is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Recent studies demonstrated that CD44 expressed in cancer cells can be proteolytically cleaved at the ectodomain by membrane type 1-matrix metalloproteinase (MT1-MMP) to form soluble CD44 and that CD44 cleavage plays a critical role in cancer cell migration. Here, we show that transforming growth factor-b (TGF-b), a multifunctional cytokine involved in cell proliferation, differentiation, migration and pathological processes, induces MT1-MMP expression in MDA-MB-435s cells. TGF-b-induced MT1-MMP expression was blocked by the specific extracellular regulated kinase-1/2 (ERK1/2) inhibitor PD98059 and the specific pho...

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The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available

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Transforming growth factor (TGF)-βs are secreted in large latent complexes consisting of TGF-β, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-β...Full Text Available

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This book contains nomographs for analysis and design of signalized intersections and thoroughly explains how to use them. The nomographs simplify and reduce the work that otherwise would have to be done by hand. The nomograph method for computing capacity has a significant advantage over computerized methods: it provides insight into the interaction between the various factors in the solution process for design analysis.

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We compare standard nuclear polarization mechanisms, ..delta..-hole-polarization and meson-exchange-current effects in the q-dependent quenching of isovector spin transitions. Calculations are performed for the M1-transition form factors of the 1/sup +/ states in /sup 48/Ca (10.23 MeV) and /sup 88/Sr (3.48 MeV). We obtain a satisfactory description of both form factors if the repulsive part of the residual interaction in the ..delta..-hole channel is of similar strength to that in the nucleon-hole channel. Meson-exchange currents lead to an enhancement of M1 transitions by an amount which is small in general, but sensitive to the particular nuclear state involved. 44 references.

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The g factors of the 2/sub 1//sup +/ states in sup(84,86,88)Sr have been deduced using the thin-foil transient field technique with the field calibration of the Rutgers group. The values are g(/sup 84/Sr)= + 0.419(47), g(/sup 86/Sr)= + 0.273(50) and g(/sup 88/Sr)= + 1.15(17). The mean lifetimes of the 2/sub 1//sup +/ states in sup(86,88)Sr were determined by the Doppler-shift attenuation method to be 2.10(22) ps and 0.219(23) ps respectively. The g factor and lifetime results are compared with shell model and interacting boson model predictions.

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In the hypothetical event of a severe accident in a Light Water Reactor, scenarios in which the reactor pressure vessel (RPV) fails and the core melt mixture (called corium) relocates into the reactor cavity, cannot be excluded. The viscosity (in fact, corium rheological behaviour) plays a major role in many phenomena such as core melt down, discharge from reactor pressure vessel, interaction with structural materials (concrete,...) and spreading in a core-catcher. For these reasons, it is important to be able to predict the rheological behaviour of corium melts of different compositions (essentially based on UO{sub 2}, ZrO{sub 2}, Fe{sub x}O{sub y} and Fe for in-vessel scenarios, plus SiO{sub 2} and CaO for ex-vessel scenarios) at temperatures above solidus temperature. In the case of corium-concrete mixtures, the increase of viscosity depends not only on the increase of particles in the melts but also on the increase of the residual liquid phase viscosity (due to ...

International Nuclear Information System (INIS)

The report addresses the application of reverse osmosis to the treatment of radioactive liquid waste, focusing on the effects of non-radioactive cations and anions, existing in radioactive waste, on the removal of radioactive nuclides. The bivalent cations are generally about ten times as high in decontamination factor as monovalent ones. In the case of anions, the factor of SO_4"2"- is about ten times that of Cl"- while that of NO_3"- is somewhat smaller than that of Cl"-. During permeation through membrane, anions tend to accompany cations, and the decontamination factor of accompanying ions is found to increase with that of the paring ions. These results indicate that if one can select components that will remain in the liquid waste, one should consider their effects on the efficiency of its treatment. Furthermore, the interaction between two anions or between two cations can be approximated by a ...

Science.gov (United States)

PMID:21331648

KoreaScience (Korea)

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KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

BackgroundThe orphan nuclear receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily. It was identified through a search for genes...Full Text Available

Science.gov (United States)

1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase inhibitors. 4. All three analogues reduced ligand ...

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An /alpha//sub 2/-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet /alpha//sub 2/-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet /alpha//sub 2/-adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the /alpha//sub 2/-adrenergic ligand (/sup 3/H)rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the /alpha//sub 2/B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet /alpha//sub 2/-adrenergic receptor (/alpha//sub 2/A) lies on chromosome 10. This ...

International Nuclear Information System (INIS)

Macrophage differentiation antigen associated with complement three receptor function (Mac-1) belongs to #beta#_2 subfamily of integrins that mediate important cell-cell and cell-extracellular matrix interactions. Biochemical studies have indicated that Mac-1 is a constitutive heterodimer in vitro. Here, we detected the heterodimerization of Mac-1 subunits in living cells by means of two fluorescence resonance energy transfer (FRET) techniques (fluorescence microscopy and fluorescence spectroscopy) and our results demonstrated that there is constitutive heterodimerization of the Mac-1 subunits and this constitutive heterodimerization of the Mac-1 subunits is cell-type independent. Through FRET imaging, we found that heterodimers of Mac-1 mainly localized in plasma membrane, perinuclear, and Golgi area in living cells. Furthermore, through analysis of the estimated physical distances between cyan fluorescent protein (CFP) and yellow fluorescent ...

Science.gov (United States)

Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the ?(2)?(1) integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS-BBB penetration. Our results suggest that the ...

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In a forthcoming paper we describe a new approach to rapidity gap survival (RGS) in the production of high-mass systems (H = dijet, Higgs, etc.) in exclusive double-gap diffractive pp scattering, pp -> p + H + p. It is based on the idea that hard and soft interactions are approximately independent (QCD factorization), and allows us to calculate the RGS probability in a model-independent way in terms of the gluon generalized parton distributions (GPDs) in the colliding protons and the pp elastic scattering amplitude. Here we focus on the transverse momentum dependence of the cross section. By measuring the ''diffraction pattern'', one can perform detailed tests of the interplay of hard and soft interactions, and even extract information about the gluon GPD in the proton from the data.

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Eugenol, the principal chemical component of clove oil from Eugenia aromatica has been long known for its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects. The interaction of the eugenol with ten different hydrophobic and hydrophilic antibiotics was studied against five different Gram negative bacteria. The MIC of the combination was found to decrease by a factor of 5-1000 with respect to their individual MIC. This synergy is because of the membrane damaging nature of eugenol, where 1mM of its concentration is able to damage nearly 50% of the bacterial membrane. Eugenol was also able to enhance the activities of lysozyme, Triton X-100 and SDS in damaging the bacterial cell membrane. The hydrophilic antibiotics such as vancomycin and b-lactam antibiotics which have ...

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The existence of multipole components in the dipole and quadrupole magnets is one of the factors limiting the beam stability in the RHIC operations. So, a realistic non-linear model is crucial for understanding the beam behavior and to achieve the ultimate performance in RHIC. A procedure is developed to build a non-linear model using the available multipole component data obtained from measurements of RHIC magnets. We first discuss the measurements performed at different stages of manufacturing of the magnets in relation to their current state in RHIC. We then describe the procedure to implement these measurement data into tracking models, including the implementation of the multipole feed down effect due to the beam orbit offset from the magnet center. Finally, the field quality analysis in the RHIC interaction regions (IR) is presented.

British Library Electronic Table of Contents (United Kingdom)

The expression of motor activity levels in response to novel situations is under complex genetic and environmental control. Several genetic loci have been implicated in the regulation of this behavioral phenotype, but their relationship to epigenetic and epistatic interactions is relatively unknown. Here, we report on a quantitative trait locus (QTL) on mouse chromosome 1 for novelty-induced motor activity in the open field, using chromosome substitution strains derived from a high active host strain (C57BL/6J) and a low active donor strain (A/J). The QTL for open field (horizontal distance moved) peaked at the location of Kcnj9, however, QTL detection was initially masked by an interplay of both grandparent genetic origin and genetic co-factors influencing behavior on chromosome 1. Our fi...

International Nuclear Information System (INIS)

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U-"1"4C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10"5 cells/ml) were incubated with either ["1"2"5I]insulin or ["1"2"5I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and "1"4C-incorporation into lipids. Insulin, hGH and PGF ...

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Results of an investigation aiming to study the effects of the burner cap design factors on flame stability are presented in this paper. Flame stability is an essential part of the operation of all domestic burners, including natural gas-fired cooktops. At high thermal inputs flame lifts are encountered above certain levels of primary aeration, whereas flashback only takes place at low thermal inputs, due to natural gas low flame speed, above certain levels of primary aeration. In this work, flame lift limits were measured at 3.3 kW thermal input and the highest primary aeration above which flame lifts started to become visible was the stability limit at this thermal input. Around 60% primary aeration was desired to minimize pollutant emissions. Turndown tests were done at 40% primary aeration. The `Factorial Experimental Design` method with statistical analysis was used. This enabled detection of interactions between ...

British Library Electronic Table of Contents (United Kingdom)

The treatment of peat with the solutions of phosphoric, citric, and oxalic acids in concentrations of 10???4 and 10???2 mol/l at solid phase to liquid ratios of 1: 2.5 and 1: 5 increased the absorption of ammonia by 6.4???39.7%. The absorption of ammonia was higher than the concentration of doping ion-exchange groups by a factor of 5???2000. With the use of EPR and IR spectroscopy, it was found that this phenomenon was caused by the transformation of polyconjugation systems as a result of the interaction of acids with the organic matrix of peat by a macrocoordination mechanism, which also improved the technological characteristics of the resulting sorbents. The absence of the destruction of organic matter with the use of low concentrations of weak acids makes it possible to use these sorbe...

International Nuclear Information System (INIS)

We compare standard nuclear polarization mechanisms, #DELTA#-hole-polarization and meson-exchange-current effects in the q-dependent quenching of isovector spin transitions. Calculations are performed for the M1-transition form factors of the 1"+ states in "4"8Ca (10.23 MeV) and "8"8Sr (3.48 MeV). We obtain a satisfactory description of both form factors if the repulsive part of the residual interaction in the #DELTA#-hole channel is of similar strength to that in the nucleon-hole channel. Meson-exchange currents lead to an enhancement of M1 transitions by an amount which is small in general, but sensitive to the particular nuclear state involved. (orig.).

International Nuclear Information System (INIS)

The magnetic scattering spectra of RAgSb_2 (R = Ho, Er, Tm) intermetallic compounds are measured and their crystal electric field parameters are determined using inelastic neutron scattering. It is revealed that the ground state is a nonmagnetic singlet for the HoAgSb_2 compound, a Kramers doublet with a strongly anisotropic g factor for the ErAgSb_2 compound, and a quasi-doublet (random doublet) characterized by an extremely anisotropic g factor for the TmAgSb_2 compound. The exchange interaction is estimated in the molecular field approximation. The magnetic properties of the RAgSb_2 compounds are analyzed in terms of the energy level schemes and eigenfunctions determined in this study. The calculated anisotropic magnetic susceptibilities for all compounds are in good agreement with the experimental data obtained for single crystals.

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A clone encoding a human D{sub 2} dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D{sub 2} receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.

Energy Technology Data Exchange (ETDEWEB)

Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.

British Library Electronic Table of Contents (United Kingdom)

Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptor activator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...

International Nuclear Information System (INIS)

Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in ...

International Nuclear Information System (INIS)

In recent years it has become evident from epidemiological and experimental data that a large number of environmental factors, including diet, play a role in modifying the incidence of cancer. Cell culture systems in which oncogenic transformation serves as an end point are powerful tools for evaluating these questions. Using such systems it has been shown recently that pyrolysis products from charred surfaces of broiled meat and fish can transform hamster embryo cells in vitro as well as produce tumors in the animal. Our studies in vitro have demonstrated the oncogenic potential of ionizing radiation in both hamster and human cells and have established in hamster cells the dose response relationship at doses ranging from 1 to 600 rad for x-rays and 0.1 to 150 rad for neutrons. The present work was aimed at evaluating whether there exists a cocarcinogenic interaction between a pyrolysis product and x-rays in their ability to transform hamster ...

International Nuclear Information System (INIS)

The magnon dispersion curve of Gd metal has been determined from first principles by use of augmented-plane-wave energy bands and wave functions. The exchange matrix elements I (k,k') between the 4f electrons and the conduction electrons from the first six energy bands were calculated under the assumption of an unscreened Coulomb interaction. The results are in good overall agreement with experiment provided the I (k,k') are diminished by a constant scale factor of about 2 which may be caused by screening.

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Transforming growth factor beta (TGF-@b) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-@b and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-@b and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role i...

Science.gov (United States)

This investigation concerns the nonlinear dynamics of heat transfer from a surface using an upstream eddy promoter. A numerical model is developed for the coupled fluid flow and heat transfer process based on a modified MacCormack scheme. Numerical simulations are carried out to determine the response and heat transfer enhancement due to the promoter. The average heat transfer from a cavity floor is seen to be increased by a factor of approximately five over the unpromoted'' flow. Another interesting feature of the study is the nonlinear viscous flow dynamics from the cylinder-wall interaction which differ significantly from the familiar cylinder-free stream patterns.

British Library Electronic Table of Contents (United Kingdom)

Purpose ? The Islamic social capital is characterised by a desire for moral values in production and networking which promotes opportunities for innovative interactions between sets of agents thus forwarding the Islamic ethics. The aim of this paper is to explore the factors that drive alliance formation between labour and capital in both financial and technological forms. Design/methodology/approach ? An in-depth study was made of developmental interventions within the Muslim community life of a village in the Birbhum district of West Bengal province in India. Findings ? Evidence shows that the strengthening of informal co-operative networks through the inputs of technology, financial, and human capital from across different sectors constitutes an essential element in forwarding sustainab...

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Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed in human peripheral blood monocytes and histiocytic leukemia ...

Science.gov (United States)

In this paper we review and classify the various patterns of isosteric heat versus loading for adsorption of gases on graphitised thermal carbon black at temperatures ranging from below the 3D triple point to temperatures above it, but less than the 3D critical point. We have identified the features of heat curve and highlighted the microscopic origin of these features. The patterns vary with temperature and with the relative strength of the fluid-fluid interaction and solid-fluid interaction. For simple adsorptives (by simple we meant there is no strong association between fluid particles), the heat curve is typified by fluid-fluid attraction and layering phenomena. For adsorptives showing strong association such as water, ammonia and methanol, the heat curve essentially begins below the condensation heat and then approaches it as loading is increased. This is mainly due to the strong hydrogen bonding in these fluids. A third group includes ...

UK PubMed Central (United Kingdom)

The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABA_A and Drosophila melanogaster...Full Text Available

UK PubMed Central (United Kingdom)

The plant hormone cytokinin is perceived by membrane-located sensor histidine kinases. Arabidopsis (Arabidopsis thaliana) possesses three cytokinin receptors: ARABIDOPSIS HISTIDINE...Full Text Available

UK PubMed Central (United Kingdom)

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation...Full Text Available

UK PubMed Central (United Kingdom)

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M₃ subtype, with the M₂...Full Text Available

UK PubMed Central (United Kingdom)

We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice....Full Text Available

UK PubMed Central (United Kingdom)

The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to...Full Text Available

UK PubMed Central (United Kingdom)

The presence of albumin structures with the capacity to bind to a surface receptor in group C and G streptococci was studied in serum samples from 45 mammalian species representing 15 different orders,...Full Text Available

UK PubMed Central (United Kingdom)

Antagonists for kainate receptors (KARs), a family of glutamate-gated ion channels, are efficacious in a number of animal models of neuropathologies, including epilepsy, migraine pain, and anxiety....Full Text Available

UK PubMed Central (United Kingdom)

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available

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Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor...Full Text Available

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The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous...Full Text Available

UK PubMed Central (United Kingdom)

TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated...Full Text Available

UK PubMed Central (United Kingdom)

OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available

UK PubMed Central (United Kingdom)

Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable...Full Text Available

UK PubMed Central (United Kingdom)

Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available

UK PubMed Central (United Kingdom)

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased κ-opioid receptor (KOR)...Full Text Available

UK PubMed Central (United Kingdom)

Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine...Full Text Available

UK PubMed Central (United Kingdom)

BACKGROUNDOff-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1...Full Text Available

International Nuclear Information System (INIS)

... carbon 14 cholera gels labelling membranes molecules proteins receptors

UK PubMed Central (United Kingdom)

P2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells...Full Text Available

UK PubMed Central (United Kingdom)

Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized....Full Text Available

Energy Technology Data Exchange (ETDEWEB)

Statistically based experimental designs were applied to optimize the fermentation process parameters for hydrogen (H{sub 2}) production by co-culture of Clostridium acidisoli and Rhodobacter sphaeroides with sucrose as substrate. An initial screening using the Plackett-Burman design identified three factors that significantly influenced H{sub 2} yield: sucrose concentration, initial pH, and inoculum ratio. These factors were considered to have simultaneous and interdependent effects. A central composite design and response surface analysis were adopted to further investigate the mutual interactions among the factors and to identify the values that maximized H{sub 2} production. The optimal substrate concentration, initial pH, and inoculum ratio of C. acidisoli to R. sphaeroides were 11.43 g/L sucrose, 7.13, and 0.83, respectively. Using these optimal culture conditions, substrate conversion efficiency ...

International Nuclear Information System (INIS)

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that ...

International Nuclear Information System (INIS)

We have measured the transverse asymmetry A_T_"' in the quasielastic "3He-vector(e-vector,e"') process with high precision at Q"2 values from 0.1 to 0.6 (GeV/c)"2. The neutron magnetic form factor G_M"n was extracted at Q"2 values of 0.1 and 0.2 (GeV/c)"2 using a nonrelativistic Faddeev calculation which includes both final-state interactions (FSI) and meson-exchange currents (MEC). Theoretical uncertainties due to the FSI and MEC effects were constrained with a precision measurement of the spin-dependent asymmetry in the threshold region of "3He-vector(e-vector,e"'). We also extracted the neutron magnetic form factor G_M"n at Q"2 values of 0.3 to 0.6 (GeV/c)"2 based on plane wave impulse approximation calculations.

Energy Technology Data Exchange (ETDEWEB)

Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone ...

Energy Technology Data Exchange (ETDEWEB)

This analysis report is one of a series of technical reports that document the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the geologic repository at Yucca Mountain. This report is one of the five biosphere reports that develop input parameter values for the biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes the conceptual model, as well as the mathematical model and its input parameters. Figure 1-1 is a graphical representation of the documentation hierarchy for the ERMYN. This figure shows relationships among the products (i.e., scientific analyses and model reports) developed for biosphere modeling and biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan for Biosphere Modeling and Expert Support'' (BSC 2005 [DIRS 172782]). The purpose of this ...

International Nuclear Information System (INIS)

In order to practice design-by-analysis of thermohydraulics design of BWR fuel rod bundles, the subchannel analysis would play a major role. There, one of the immediate concerns is improvement in its predictive capability of boiling transition phenomena on the fuel rod surface. This capability strongly depends on the modeling of thermohydraulics phenomena of interests: 1) vapor-liquid redistribution by inter-subchannel exchanges due to the diversion cross flow, turbulent mixing and void drift, 2) liquid film behaviors, 3) transition of two-phase flow regimes, 4) droplet entrainment and deposition and 5) spacer-droplet interactions. These are considered to be five key factors in understanding the BT in BWR fuel rod bundles. This paper describes a progress and current status in the second year of the three year project on developing generalized boiling transition models with the above five key factors being focused on. A ...

Energy Technology Data Exchange (ETDEWEB)

During outbreaks, Microdiprion pallipes (Fall.) is the most destructive of the pine sawflies in Sweden. Its distribution includes most provinces, but damaging outbreaks have until recently occurred only in two inland areas in northern Sweden. These areas are characterised by high elevation, a harsh climate, and slow tree growth. The four recorded outbreak periods showed a 10 year periodicity. Outside these areas, a lesser outbreak occurred in 1988 to 1990, on the east coast (province of Uppland). Outbreak patterns, life history variation, and mortality factors were studied. Factors that may explain the distribution of outbreaks and the population patterns were identified.Experimental and observational evidence on the potential of various factors to influence fecundity, dispersal, and survival was evaluated. In the outbreak areas, there were few major population factors. Parasitism by Rhorus substitutor ...

International Science & Technology Center (ISTC)

Research of Cumulative Jets Interaction with Spent Nuclear Fuel

CERN Document Server

An Introduction to the Standard Theory of Electroweak Interactions (3/4)

International Nuclear Information System (INIS)

Single-crystal neutron diffraction has been used to observe the interactions between deuterated ethanol (CD3CD2OH) and lysozyme in triclinic crystals of hen egg white lysozyme soaked in 25% (v/v) ethanol solutions. A total of 6047 observed reflections to a resolution of 2 A were used, and 13 possible ethanol sites were identified. The three highest occupied sites are close to locations for bromoethanol found in an earlier study by Yonath et al. [Yonath, A., Podjarny, A., Honig, B., Traub, W., Sielecki, A., Herzberg, O., and Moult, J. (1978) Biophys. Struct. Mech. 4, 27-36]. Structure refinements including a model for the flat solvent lead to a final crystallographic agreement factor of 0.097. Comparison with earlier neutron studies on triclinic lysozyme showed that neither the molecular structure nor the thermal motions were affected significantly by the ethanol. A detailed analysis of the ethanol-lysozyme contacts showed 61% of these to be ...

CERN Document Server

Neutrino emission drives neutron star cooling for the first several hundreds of years after its birth. Given the low energy ($\\sim$ keV) nature of this process, one expects very few nonstandard particle physics contributions which could affect this rate. Requiring that any new physics contributions involve light degrees of freedom, one of the likely candidates which can affect the cooling process would be a nonzero magnetic moment for the neutrino. To illustrate, we compute the emission rate for neutrino pair bremsstrahlung in neutron-neutron scattering through photon-neutrino magnetic moment coupling. We also present analogous differential rates for neutrino scattering off nucleons and electrons that determine neutrino opacities in supernovae. Employing current upper bounds from collider experiments on the tau magnetic moment, we find that the neutrino emission rate can exceed the rate through neutral current electroweak interaction by a ...

Energy Technology Data Exchange (ETDEWEB)

A micro-mechanistic understanding of bone fracture that encompasses how cracks interact with the underlying microstructure and defines their local failure mode is lacking, despite extensive research on the response of bone to a variety of factors like aging, loading, and/or disease. Micro-mechanical models for fracture incorporating such local failure criteria have been widely developed for metallic and ceramic materials systems; however, few such deliberations have been undertaken for the fracture of bone. In fact, although the fracture event in mineralized tissues such as bone is commonly believed to be locally strain controlled, until recently there has been little experimental evidence to support this widely held belief. In the present study, a series of in vitro experiments involving a double-notch bend test geometry are performed in order to shed further light on the nature of the local cracking events that precede catastrophic fracture ...

CERN Document Server

While sharing resources the efficiency is substantially degraded as a result of the scarceness of availability of the requested resources in a multiclient support manner. These resources are often aggravated by many factors like the temporal constraints for availability or node flooding by the requested replicated file chunks. Thus replicated file chunks should be efficiently disseminated in order to enable resource availability on-demand by the mobile users. This work considers a cross layered middleware support system for efficient delay-sensitive streaming by using each device's connectivity and social interactions in a cross layered manner. The collaborative streaming is achieved through the epidemically replicated file chunk policy which uses a transition-based approach of a chained model of an infectious disease with susceptible, infected, recovered and death states. The Gossip-based stateful model enforces the mobile nodes whether to ...

Energy Technology Data Exchange (ETDEWEB)

The murine 3T3-L1 fibroblast under appropriate incubation conditions differentiates into an adipocyte phenotype. This 3T3-L1 adipocyte exhibits many of the morphologic, biochemical, and insulin-responsive features of the normal rodent adipocyte. Using quantitative electron microscopic (EM) autoradiography we find that, when /sup 125/I-insulin is incubated with 3T3-L1 adipocytes, the ligand at early times of incubation localizes to the plasma membrane of the cell preferentially to microvilli and coated pits. When the incubation is continued at 37 degrees C, /sup 125/I-insulin is internalized by the cells and preferential binding to the villous surface is lost. With the internalization of the ligand, two intracellular structures become labeled, as determined by the method of hypothetical grain analysis. These include large clear, presumably endocytotic, vesicles and multivesicular bodies. Over the first hour of incubation the labeling of these structures increases in parallel, but in the ...

Energy Technology Data Exchange (ETDEWEB)

Most analyses of the alternative strategies used by utilities to comply with Title IV requirements have focused on factors directly related to controlling sulfur dioxide (SO{sub 2}) emissions. However, utilities must meet a number of additional environmental requirements at the same tune they comply with the acid rain program. To illuminate the potential synergies and conflicts that might exist between the other regulatory mandates and the acid rain program, a thorough examination of all the various programs and their interrelationships must be conducted. This paper reviews the environmental mandates that utilities will have to plan to meet in the next decade concurrently with the acid rain program, and it analyzes the interactions among the various programs to identify potential synergies and conflicts.

British Library Electronic Table of Contents (United Kingdom)

MINER?A is a high resolution, fully active detector designed to study neutrino interactions on nuclei in the NuMI beam at Fermi National Accelerator Laboratory. The active volume of the detector consists of 3 tons of plastic scintillator and includes embedded targets of 4He, C, H2O, Fe and Pb. The MINER?A collaboration expects to perform precision, A-dependent neutrino cross section measurements in the 1?10 GeV region, measure the axial form factor, and study nuclear shadowing of F2, quark-hadron duality and coherent pion production, among other topics. MINER?A began data taking in the fall of 2009. This paper describes the MINER?A experiment and provides an overview of the physics objectives along with estimated uncertainties of the measurements and the tentative projected schedule of dat...

International Nuclear Information System (INIS)

Measurements are made on the principal magnetic susceptibilities and anisotropies of praseodymium selenate octahydrate single crystals in the temperature range 90 to 300 K. Although the effective magnetic moment is close to the free ion value, the anisotropy is quite high at room temperature. A least sequares fit of the Curie-Weiss law to the observed average susceptibility yields -36.5 K as the paramagnetic Curie temperature. An analysis of the results with a crystal field (CF) of D_4 symmetry, explains the observed results quite well. The CF and the spin-orbit interaction matrix is block diagonalized in the complete 33 dimensional basis of the "3H term in order to obtain the Stark energies and their eigenstates. Intermediate coupling effects are also considered. The ground state being a singlet, the g-factors are absent. Some predictions on the electronic heat capacity and the electronic quadrupole splitting are made in the light of the ...

Science.gov (United States)

The kinetic rate constants for the cracking, isomerization, and disproportionation of n-heptane over a CrHNaY (32% chromium exchanged) zeolite catalyst at 400, 450, and 470/sup 0/C have been calculated. The interaction of n-heptane with a model Lewis acid such as BF/sub 3/ and progress along the reaction coordinate have been studied by means of molecular orbital calculations. From the kinetic results, i.e., activation energies and frequency factors, and the theoretical calculations, it can be concluded that the controlling step in these reactions is not the formation of the carbonium ion, but the subsequent transformation of this carbonium ion. In addition, the theoretical calculations show that the attack of a Lewis acid is more likely to occur on a carbon atom than on a C-H bond.

British Library Electronic Table of Contents (United Kingdom)

Temperature variations due to climate changes are a major cause of movements in a concrete structure, both in the longitudinal and transversal directions and between different parts of the structure. If these movements are restrained, stresses will be induced which may contribute to cracking. The movements are caused by complex interactions of several factors such as solar radiation, air temperature, long-wave heat radiation and wind speed. To predict the varying thermal conditions in a concrete structure a finite element model has been used. A validation of the model has been performed using field measurements in a concrete slab together with climate data from the Swedish Meteorological and Hydrological Institute to be able to use the model for simulations over long time periods and for s...

British Library Electronic Table of Contents (United Kingdom)

Immune thrombocytopenic purpura (ITP), Guillain-Barre syndrome (GBS), and Hashimotos thyroiditis (HT) are autoimmune disorders caused by impaired self-tolerance mechanisms triggered by interaction between genetic and environmental factors. ITP is an immune-mediated destruction of platelets resulting in mucocutaneous bleeding, GBS is an ascending motor paralysis caused by an inflammatory demyelination of peripheral nerves, and HT is characterized by autoimmune-mediated destruction of the thyroid gland. The concurrent development of ITP and GBS has only rarely been reported in the literature, and GBS itself rarely occurs with other autoimmune disorders. We present a 21 year-old patient with known Hashimotos hypothyroidism that simultaneously developed GBS and ITP after an upper respiratory t...

British Library Electronic Table of Contents (United Kingdom)

The sediment content of the Yellow River is resulted from the interactions of natural, economic, and social factors, so it includes some evolutive information of the Yellow River Basin system. Sediment contents from 1952 to 2007 on Toudaoguai, Tongguan, Huayuankou and Lijin sections along the river are chosen as the study time series, and correlation dimensions (D 2), Kolmogorov entropies (K 2), and Hurst indexes (H) of the time series were calculated. Correlation dimensions on Toudaoguai, Tongguan, Huayuankou, and Lijin sections are 3.24, 5.69, 6.57 and 7.34 respectively, and the Kolmogorov entropies are 0.13, 0.37, 0.40 and 0.38 respectively, which indicates that the systems controlled by different sections along the Yellow River are chaotic systems and the chaotic degrees increase gradu...

British Library Electronic Table of Contents (United Kingdom)

There is increasing evidence that adolescence, like early life, is a sensitive period in which ongoing brain development can be influenced by environmental factors. This review describes our use of social instability as a model of mild adolescent social stress, its effects on social interactions and on hypothalamic?pituitary?adrenal function over the course of the procedure and in response to new stressors. The effects of social instability are sex-specific, with qualitative differences between the sexes on HPA function over the course of the stressor procedure, and with greater effects in males on behaviour observed during the social instability and greater effects in females on behavioural responses to drugs of abuse into adulthood, long after the stress exposure. The results from invest...

CERN Document Server

We introduce a methodology for analysis of multiwavelength data from X-ray selected BL Lac (XBL) objects detected in the TeV regime. By assuming that the radio--through--X-ray flux from XBLs is nonthermal synchrotron radiation emitted by isotropically-distributed electrons in the randomly oriented magnetic field of a relativistic blazar jet, we obtain the electron spectrum. This spectrum is then used to deduce the synchrotron self-Compton (SSC) spectrum as a function of the Doppler factor, magnetic field, and variability timescale. The variability timescale is used to infer the comoving blob radius from light travel-time arguments, leaving only two parameters. With this approach, we accurately simulate the synchrotron and SSC spectrum of flaring XBLs in the Thomson through Klein-Nishina regimes. Photoabsorption by interactions with internal jet radiation and the intergalactic background light (IBL) is included. Doppler ...

CERN Document Server

We present a fully relativistic formalism for describing neutrino-induced $\\Delta$-mediated single-pion production from nuclei. We assess the ambiguities stemming from the $\\Delta$ interactions. Variations in the cross sections of over 10% are observed, depending on whether or not magnetic-dipole dominance is assumed to extract the vector form factors. These uncertainties have a direct impact on the accuracy with which the axial-vector form factors can be extracted. Different predictions for $C_5^A(Q^2)$ induce up to 40-50% effects on the $\\Delta$-production cross sections. To describe the nucleus, we turn to a relativistic plane-wave impulse approximation (RPWIA) using realistic bound-state wave functions derived in the Hartree approximation to the $\\sigma$-$\\omega$ Walecka model. For neutrino energies larger than 1 GeV, we show that a relativistic Fermi-gas model with appropriate binding-energy correction produces ...

Science.gov (United States)

The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that ...

International Nuclear Information System (INIS)

The epithermal cross section shielding methods used in the lattice physics code EPRI-CELL (E-C) have been extensively studied to determine its major approximations and to examine the sensitivity of computed results to these approximations. The study has resulted in several improvements in the original methodology. These include: treatment of the external moderator source with intermediate resonance (IR) theory, development of a new Dancoff factor expression to account for clad interactions, development of a new method for treating resonance interference, and application of a generalized least squares method to compute best-estimate values for the Bell factor and group-dependent IR parameters. The modified E-C code with its new ENDF/B-V cross section library is tested for several numerical benchmark problems. Integral parameters computed by EC are compared with those obtained with point-cross section Monte Carlo ...

International Nuclear Information System (INIS)

The authors have been involved for the last few years in developing high affinity sigma-receptor-specific radiopharmaceuticals for use in nuclear medicine. They recently demonstrated that sigma-1 receptors are expressed in human melanoma cells and that sigma receptors could be used as external markers for non-invasive imaging. In order to determine the presence of sigma receptors in other human tumors they have screened numerous non-small cell lung carcinoma, melanoma and breast cancer cell lines. All of these cell lines expressed high sigma receptor densities using commercially available ["3H]-(+)-pentazocine or ["3H]DTG tritiated sigma ligands. Therefore, a sigma ligand with high affinity in both sigma-1 and sigma-2 subtype pharmacological assays could be potentially useful for imaging a variety of primary and metastatic sites of various origins. The authors describe recent ...

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

The rejection thresholds of Phormia regina Meigen for twenty-four glycols have been determined. A definite relationship between the concentration of the test material and the distribution...Full Text Available

Science.gov (United States)

... estrogen receptor status. Cancer Lett., 253, 291-300. 39. Xin,X ... and resistant mice. Brain Res.Bull., 52, 235-242. 40. Foster,BA ...

KoreaScience (Korea)

Full Text Available

UK PubMed Central (United Kingdom)

BackgroundWhereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development,...Full Text Available

Science.gov (United States)

... Title : ERG Expression Levels in Prostate Tumors Reflect Functional Status of the Androgen Receptor (AR) as a Consequence of Fusion of ERG ...

UK PubMed Central (United Kingdom)

OBJECTIVES:To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies...Full Text Available

Science.gov (United States)

... Naja oxiana neurotoxin 1, Bungarus multicinctus or-bungarotoxin) and short-chain group (Naja naja atra cobrotoxin, Naja oxiana neurotoxin 11. ...

International Nuclear Information System (INIS)

Objectives: To minimize movement artifacts during tracer imaging studies, the animals are generally sedated. Although many reports describe the effect of barbiturates on brain function, less is published about the general impact on the extracerebral metabolism and tracer biodistribution. This report describes the influence of pentobarbital on tumor uptake of ["1"2"3I]-2-iodo-L-phenylalanine (["1"2"3I]-2I-L-PA) using dissection and nuclear imaging. Methods: R1M tumor-bearing athymic mice were divided into two populations: untreated and pentobarbital-treated. Each group was subjected to dynamic and static planar imaging and organ dissection after ["1"2"3I]-2I-L-PA injection. Two-compartment blood modeling was performed. Analysis of variance (ANOVA), t test and clustered boxplot analyses were used to compare the results between the treatment groups and between the data acquisition methods. Results: Two-compartment blood modeling demonstrated that pentobarbital decreased the elimination ...

Energy Technology Data Exchange (ETDEWEB)

Background: In an effort to standardise radiological practices in the Republic of Ireland, current legislation states that 'written protocols for every type of standard radiological practice shall be established'. In order to fulfil this requirement the Irish Medical Council recommends the protocols issued by the Commission of European Communitees (CEC) for adoption in the country. Whilst this document does provide good guidance with regard to various radiographic factors, patient shielding instructions are notably ambiguous. The aim of this study was to remove some of this ambiguity by defining the optimal method of positioning patient shielding in antero-posterior (AP) and lateral lumbar spine radiographic examinations. These projections were chosen on the basis of their area of coverage being in close to and in some cases including the reproductive organs. They also represent the highest source of collective population dose of any conventional ...

Energy Technology Data Exchange (ETDEWEB)

To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, ...

Science.gov (United States)

Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated ...

International Nuclear Information System (INIS)

Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly ...