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 ...
Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine...Full Text Available
BackgroundActivation of the signal transducer and activator of transcription 3 (STAT3) within antigen presenting cells (APCs) is linked to abnormal APCs differentiation and function....Full Text Available
Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study...Full Text Available
IntroductionTyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine...Full Text Available
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
IL-4-induced Stat6 signaling is active in a variety of cell types and plays a role in cell proliferation/growth and resistance to apoptosis. Using EMSA, we identified differential IL-4/Stat6 activities in colorectal cancer cell lines, HT-29 being active Stat6"h"i"g"h phenotype and Caco-2 being defective Stat6"n"u"l"l phenotype, respectively. Active Stat6"h"i"g"h HT-29 cells exhibited resistance to apoptosis by flowcytometry and aggressive metastasis by Transwell assay compared with defective Stat6"n"u"l"l Caco-2 cells. Comparing one another using RT-PCR, Stat6"h"i"g"h HT-29 cells expressed more mRNA of anti-apoptotic and pro-metastatic genes Survivin, MDM2, and TMPRSS4, while Stat6"n"u"l"l Caco-2 cells expressed more mRNA of pro-apoptotic and anti-metastatic genes BAX, CAV1, and P53, respectively. This is the first study ...
The effects of low concentrations (10 nm or less) of indoleacetic acid and abscisic acid on the phytochrome-mediated attachment of barley root (Hordeum vulgare L., var. Compana)...Full Text Available
Social organisms that cooperate with some members of their own species, such as close relatives, may fail to cooperate with other genotypes of the same species. Such noncooperation may take the form...Full Text Available
BackgroundThe effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate (AMP) challenge...Full Text Available
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
The endophytic fungus Trichothecium roseum LZ93 from Maytenus hookeri was found to antagonize other pathogenic fungi in vitro. To identify which compound contributed substantially to the antagonism, we fermented the strain and purified its fermentation products. Eleven compounds were obtained, including two trichothecenes, five rosenonolactones, two cardiotonic cyclodepsipeptides, and two sterols. Compound 11?-hydroxyrosenonolactone (1) was assigned according to 1D and 2D-NMR data for the first time. At the same time, the 1H and 13C-NMR assignments for 6?-hydroxyrosenonolactone (2) were revised. Of all of them, only trichothecin (6) showed strong antifungal activity. Based on our observations of the antagonistic activity and the other experimental results, we suggest that the antifungal co...
AimsIt is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus.MethodsA...Full Text Available
The effect of A1-adenosine receptor antagonism via 8-cyclopentyl-1,3-dipropyl-xanthine (CPDPX) on the stimulation of skeletal muscle glucose uptake by...Full Text Available
The phytochrome-mediated attachment of mung bean (Phaseolus vulgaris L., var. Oklahoma 612) root tips on glass is quickly affected by indoleactic acid and abscisic acid at concentrations...Full Text Available
Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available
RooStats is a project to create advanced statistical tools required for the analysis of LHC data, with emphasis on discoveries, confidence intervals, and combined measurements. The idea is to provide the major statistical techniques as a set of C++ classes with coherent interfaces, which can be used on arbitrary model and datasets in a common way. The classes are built on top of RooFit, which provides a very convenient functionality for modeling the probability density functions or the likelihood functions, required as inputs for any statistical technique. Furthermore, RooFit provides the functionality for easily creating models, for analysis combination and for digital publication of the likelihood function and the data. We will present in detail the design and the implementation of the different statistical methods of RooStats. These include various classes for interval estimation and for hypothesis test depending on different statistical ...
Objective: : Evaluate expression of inducible negative regulators of JAK/STAT pathway and their target proteins during the course of ligature-induced experimental periodontal disease in rats. Design: : Rats were sacrificed 07, 15 and 30days after disease induction for histological evaluation of periodontal inflammation and macroscopic analysis of alveolar bone loss. SOCS expression and the activation status of STAT1 and STAT3 were evaluated in gingival biopsies by real time PCR and Western blot. Results: : Ligature-induced model presented significant progressive bone loss from 7 to 30days. Inflammation was evident and similar for 07 and 15days; however, a decrease on severity at the end of the experimental period was observed. There was a significant (p<0.05) increase on SOCS1 and SOCS3 ge...
The influence of low-frequency electromagnetic field irradiating by high-voltage transmission lines on signal transduction of cell in spleen cells of the rates have been studied by molecular-biology techniques. The spleen cells are extracted from skilled rates, which are exposed in the electromagnetic field of high-voltage transmission lines with 4000 V/m and 0.09-0.1 G about 400 days. The quantity or level of phosphorylation of signal transducer and activator of transcription (STAT3) in JAK-STAT signal transduction pathway of spleen cells, which are stimulated and unstimulated by IL-2, respectively, are detected by the immunoblotting and immunobiochemistry. The results show that the expression of phospho-STAT3 in spleen cell stimulated by IL-2 differ not from that in the unstimulated cell. The former is significantly large than the latter. This shows that signal transduction of cell is affected by this electromagnetic ...
Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that...Full Text Available
Jul 16, 2011 ... The standard filtering applies to all the existing distribution methods/media. ... needed to allow your data point(s) to be added to the MOA lightcurve. .... name="t1" value="0.00" unit="sigma" ucd="stat.snr" />
The GBM location uncertainties range from 5-15deg (radius, 1 sigma, stat+sys). ... The site's dis/enabling on Notice types and their other filter criteria .... Fermi Pointing Direction Notice gives the current pointing direction of the ...
The authors describe an effect of suppression of invasion of the guinea pig eye conjunctiva and the HEp-2 epithelial cells by virulent Sh. flexneri bacilli, with a simultaneous administration of the same dose of avirulent shigella mutants, genetically connected with them. The data of morphological study and experiments with 3H-glucose labeled shigellae carried out on the cell species model indicated that the bacterial competition for the specific sites for absorption on the epithelial cells underlay the observed phenomenon. PMID:331774
The resistance to microbe damages of aqueous solutions of cutting fluids (SOZh), which contain dual and more complex mixtures of known compounds, is studied. Lauric acid, myristic and tridecanic acid give microbic resistance to the compositions of synthetic cutting fluids. A complexing of the compositions as a rule does not support precisely expressed effects of synergism or antagonism.
This bibliographical study compiles and analyzes findings about the metabolism and resorption of molybdenum. Besides including studies on the physiology of molybdenum 99, a general survey is given on molybdenum in the environment and on its physiological behaviour. In particular, information on the dependence of molybdenum resorption on various factors, such as the chemical form, antagonisms etc., are gathered from literature. These factors have to be considered for sensibly carrying out necessary experiments.
Evidence is reported for a narrow structure near the J/{psi}{phi} threshold in exclusive B{sup +} {yields} J/{psi}{phi}K{sup +} decays produced in {bar p}p collisions at {radical}s = 1.96 TeV. A signal of 14 {+-} 5 events, with statistical significance in excess of 3.8 standard deviations, is observed in a data sample corresponding to an integrated luminosity of 2.7 fb{sup -1}, collected by the CDF II detector. The mass and natural width of the structure are measured to be 4143.0 {+-} 2.9(stat) {+-} 1.2(syst) MeV/c{sup 2} and 11.7{sub -5.0}{sup +8.3}(stat) {+-} 3.7(syst) MeV/c{sup 2}.
A data analysis based on an artificial neural network classifier is proposed to identify cosmic ray antiprotons detected with the CAPRICE silicon-tungsten imaging calorimeter against electron background in the energy range 1.2-4.0 GeV. A set of new physical variables, describing the events inside the calorimeter on the base of their different patterns, are introduced in order to discriminate between hadronic and electromagnetic showers. The ability of the artificial neural network classifier to perform a careful multidimensional analysis gives the possibility to identify antiprotons with an electron rejection 408{+-}85 (stat) at 95.0{+-}0.2 (stat)% of signal detection efficiency. The high accuracy achieved by this method improves substantially the efficiency in the evaluation of the cosmic ray antiproton spectrum. (orig.).
This study reports the observation of the decays B{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -} and B{sup 0}{yields}D{sup (*)-}K{sup +} in a sample of 230 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} events collected with the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} storage ring, located at the Stanford Linear Accelerator Center. The branching fractions {beta}(B{sup 0} {yields} D{sup +}{sub S}{pi}{sup -}) = (1.3 {+-} 0.3 (stat) {+-} 0.2 (syst)) x 10{sup -5}, {beta}(B{sup 0} {yields} D{sup +}{sub S}K{sup +}) = (2.5 {+-} 0.4 (stat) {+-} 0.4 (syst)) x 10{sup -5}, {beta}(B{sup 0}{yields}D{sup (*)+}{sub S}{pi}{sup -}) = (2.8 {+-} 0.6 (stat) {+-} 0.5 (syst)) x 10{sup -5}, and {beta}(B{sup 0}{yields}D{sup (*)-}K{sup +}) = (2.0 {+-} 0.5 (stat) {+-} 0.4 (syst)) x 10{sup -5} are measured. The significance of the measurements to differ from zero are 5, 9, 6, and 5 standard deviations, ...
The present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined. PMID:1435078
First results are presented from an analysis of data from the DRIFT-IIa and DRIFT-IIb directional dark matter detectors at Boulby Mine in which alpha particle tracks were reconstructed and used to characterise detector performance--an important step towards optimising directional technology. The drift velocity in DRIFT-IIa was [59.3 +/- 0.2 (stat) +/- 7.5 (sys)] m/s based on an analysis of naturally-occurring alpha-emitting background. The drift velocity in DRIFT-IIb was [57 +/- 1 (stat) +/- 3 (sys)] m/s determined by the analysis of alpha particle tracks from a Po-210 source. 3D range reconstruction and energy spectra were used to identify alpha particles from the decay of Rn-222, Po-218, Rn-220 and Po-216. This study found that (22 +/- 2)% of Po-218 progeny (from Rn-222 decay) are produced with no net charge in 40 Torr CS2. For Po-216 progeny (from Rn-220 decay) the uncharged fraction is (100 +0 -35)%.
Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the h_b(1P) spin-singlet partner of the P-wave chi_b(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4 (stat.) +/- 1 (syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.0 sigma, including systematic uncertainties. We obtain the value (3.7 +/- 1.1 (stat.) +/- 0.7 (syst.))x 10^{-4} for the product branching fraction BF(Upsilon(3S) --> pi0 h_b) x BF(h_b --> gamma eta_b).
The intrinsic decay rate of orthopositronium formed in SiO/sub 2/ powder is measured using the direct 2 gamma correction method such that the time dependence of the pick-off annihilation rate is precisely determined. The decay rate of orthopositronium is found to be 7.0396+or-0.0012(stat.)+or-0.0011(sys.)/ mu s/sup -1/, which is consistent with our previous measurements with about twice the accuracy. Results agree well with the O( alpha /sup 2/) QED prediction, and also with a result reported very recently using nanoporous film.
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 antagonistic to cadmium as counterposition. Showing those possibilities was the aim of the present paper.
Mutations in sclerostin function or expression cause sclerosing bone dysplasias, involving decreased antagonism of Wnt/Lrp5 signaling. Conversely, deletion of the VHL tumor suppressor in osteoblasts, which stabilize HIF-a isoforms and thereby enables HIF-a/b-driven gene transcription, increases bone mineral content and cross-sectional area compared to wild-type controls. We examined the influence of cellular hypoxia (1% oxygen) upon sclerostin expression and canonical Wnt signaling. Osteoblasts and osteocytes cultured under hypoxia revealed decreased sclerostin transcript and protein, and increased expression and nuclear localization of activated b-catenin. Similarly, both hypoxia and the hypoxia mimetic DFO increased b-catenin gene reporter activity. Hypoxia and its mimetics increased exp...
Extraction of hafnium by 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (HL) in benzene, toluene, chloroform and tetrachloromethane from aqueous-alcoholic solutions of the formal acidity of 2M-HClO_4 was studied. Methyl, ethyl, n- and isopropyl, tert-butyl and allyl alcohol as well as ethylene glycol monomethyl ether and propylene glycol were used as organic components of the mixed aqueous-organic phase. Their presence in some cases resulted in a synergic increase in the distribution ratio of hafnium. The increase is interpreted using the results of a slope analysis and measurements of the alcohol distribution and the relative permittivity of the organic phase. It is suggested that HfL_4 molecules were solvated by alcohol molecules in the organic phase. At high alcohol concentration synergism changed into antagonism. This was caused by changes in the distribution of HL and its interaction with the alcohol in the organic phase. (author).
This article presents a hands-on web-based activity motivated by the relation between human health and ozone pollution in California. This case study is based on multivariate data collected monthly at 20 locations in California between 1980 and 2006. Several strategies and tools for data interrogation and exploratory data analysis, model fitting and statistical inference on these data are presented. All components of this case study (data, tools, activity) are freely available online at: http://wiki.stat.ucla.edu/socr/index.php/SOCR_MotionCharts_CAOzoneData. Several types of exploratory (motion charts, box-and-whisker plots, spider charts) and quantitative (inference, regression, analysis of variance (ANOVA)) data analyses tools are demonstrated. Two specific human health related questions...
In light of the recent discovery of the importance of the isovector EMC effect for the interpretation of the NuTeV determination of sin^2 theta_W, it seems timely to reassess the central value and the errors on this fundamental Standard Model parameter derived from the NuTeV data. We also include earlier work on charge symmetry violation and the recent limits on a possible asymmetry between s and \\bar{s} quarks. With these corrections we find a revised NuTeV result of sin^2 theta_W = 0.2232 \\pm 0.0013(stat) \\pm 0.0024(syst), which is in excellent agreement with the running of sin^2 theta_W predicted by the Standard Model.
AbstractTrends in Nanotechnology (TNT2009) This special issue of Physica Status Solidi presents representative contributions describing the main topics covered at the 10th Trends in Nanotechnology (TNT2009) International Conference, held in Barcelona (Spain), September 07 11, 2009. During the last years many international or national conferences have emerged in response to the growing awareness of the importance of nanotechnology as key issue for the future scientific and technological development. Among these, the conference series Trends in Nanotechnology has become one of the most important meeting points in the nano technology field: it provides fresh organisation ideas, brings together well known speakers, and promotes a suitable environment for discussions, exchanging ideas, enhancin...
The photon-proton total cross section has been measured in the process e{sup +}p{yields}e{sup +}{gamma}p{yields}e{sup +}X with the ZEUS detector at HERA. Events were collected with photon virtuality Q{sup 2}<0.02 GeV{sup 2} and average {gamma}p center-of-mass energy W{sub {gamma}}{sub p}=209 GeV in a dedicated run, designed to control systematic effects, with an integrated luminosity of 49 nb{sup -1}. The measured total cross section is {sigma}{sub tot}{sup {gamma}}{sup p}=174{+-}1 (stat.){+-}13 (syst.) {mu}b. The energy dependence of the cross section is compatible with parameterizations of high-energy pp and pp-bar data.
Limestone dissolution rate was measured by a pH-stat method with CO(2) sparging and dissolved sulfite. The dissolution rate of limestone under these conditions was found to be controlled by mass transfer and surface kinetics. As can be seen from the results, in the presence of sulfite, limestone dissolution rate increases with increasing stirring speed, reaction temperature and CO(2) partial pressure. The crystallinity of limestone has a great impact on the dissolution rate: The lower the value of the crystallinity of limestone is, the higher the dissolution rate is. The presence of sulfite promotes the dissolution rate when pH value is below 5.5 but inhibits it when pH value is above 5.5. PMID:19359093
The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC"5"0 0.83-24@mg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-pho...
Abstract Sam68 (Src-associated protein in mitosis 68-kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein,...
The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Each time this trait evolves, novel solutions to the problem posed by vertebrate hemostasis are generated. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Molecular approaches (termed 'sialomics') to characterize the full inventory of mRNAs transcribed in salivary glands have revealed a surprising level of complexity within a single species. Multiple salivary proteins may be ...
We report the first observation of the radiative decay B^0 -> \\phi K^0 \\gamma using a data sample of 772 x 10^6 B B-bar pairs collected at the \\Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^+e^- collider. We observe a signal of 37+/-8 events with a significance of 5.4 standard deviations including systematic uncertainties. The measured branching fraction is ${\\cal B}(B^0 -> \\phi K^0 \\gamma) = (2.74\\pm 0.60 \\pm 0.32) \\times 10^{-6}$, where the uncertainties are statistical and systematic, respectively. We also report the first measurements of time-dependent CP violation parameters: ${\\mathcal S}_{\\phi K_S^0 \\gamma} = +0.74^{+0.72}_{-1.05} (stat)^{+0.10}_{-0.24} (syst)$ and ${\\mathcal A}_{\\phi K_S^0 \\gamma} = +0.35 +/- 0.58 (stat)^{+0.23}_{-0.10} (syst)$. Furthermore, we measure ${\\mathcal B}(B^+ -> \\phi K^+ \\gamma) = (2.48 +/- 0.30 +/- 0.24) x 10^{-6}$, ${\\mathcal A}_{CP} = -0.03 +/- ...
The renewed CDF II experiment recently re-started data taking. The data collected lately already provides insight in the heavy flavor capabilities of this p{bar p} experiment. As a benchmark of these possibilities we present two preliminary results: the measurement of the branching fractions BR(D{sup o} {yields} {pi}{sup +}{pi}{sup -}) and BR(D{sup o} {yields} K{sup +}K{sup -}) relative to BR(D{sup o} {yields} K{sup {+-}} {pi}{sup {-+}}) and the measurement of the invariant mass difference between D{sub s}{sup {+-}} {yields} {phi}{pi}{sup {+-}}, {phi} {yields} K{sup +}K{sup -} and D{sup {+-}} {yields} {phi}{pi}{sup {+-}}, {phi} {yields} K{sup +}K{sup -}. The preliminary results are BR(D{sup o} {yields} {pi}{sup +}{pi}{sup -})/BR(D{sup o} {yields} K{sup {+-}} {pi}{sup {-+}}) = 3.37 {+-} 0.20(stat) {+-} 0.16(sys)%, BR(D{sup o} {yields} K{sup +}K{sup -})/BR(D{sup o} {yields} K{sup {+-}} {pi}{sup {-+}}) = 11.17 {+-} 0.98(sys) % and {Delta}m (D{sub s} - D{sup +}) = ...
Arsenic in soils from the Asarco lead smelter in East Helena, Montana was characterized by X-ray absorption spectroscopy (XAS). Arsenic oxidation state and geochemical speciation were analyzed as a function of depth (two sampling sites) and surface distribution. These results were compared with intensive desorption/dissolution experiments performed in a pH stat reactor for samples from the site with the highest degree of As heterogeneity. The objectives of the study were to investigate the solid-phase geochemical As speciation, assess the speciation of As in solutions equilibrated with the solids under controlled pH (pH=4 or 6) and Eh (using hydrogen or air) environments, observe the effects of phosphate on the release of As into solution, and examine the effects of phosphate on metal mobility in the systems. Arsenic was predominantly found in the As(V) valence state, though there was evidence that As(III) and As(0) were present also. The dominant geochemical phase ...
Directed evolution of proteins depends on the production of molecular diversity by random mutagenesis. While a number of methods have been developed for introducing this diversity, the best ways to sample it are not always clear. Here we used simple statistics to analyse completeness and diversity in randomized libraries generated by oligonucleotide-directed mutagenesis, error-prone polymerase chain reaction (epPCR) and in vitro recombination of highly homologous sequences. For oligonucleotide-directed mutagenesis, we derive equations to estimate how complete a given library is expected to be and also to predict the size of library required to give a fixed probability of being 100% complete. We describe the statistical bases for computer programs which estimate the number of distinct variants represented in epPCR and shuffled libraries, dubbed PEDEL and DRIVeR, respectively. These programs allow the user to calculate (rather than guess) the diversity represented in a given library and ...
We present a measurement of the t{bar t} production cross section using events with one charged lepton and jets from p{bar p} collisions at a center-of-mass energy of 1.96TeV. In these events, heavy flavor quarks from top quark decay are identified with a secondary vertex tagging algorithm. From 162 pb{sup -1} of data collected by the Collider Detector at Fermilab, a total of 48 candidate events are selected, where 13.5 {+-} 1.8 events are expected from background contributions. We measure a t{bar t} production cross section of 5.6{sub -1.1}{sup _1.2}(stat.){sub -0.6}{sup +0.9}(syst.)pb.
Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms ...
In a previous study, to identify genes of importance for hepatocellular carcinogenesis, and especially for processes involved in malignant transformation, the authors investigated differences in gene expression between adenomas and carcinomas by DNA microarray. In the present study, the authors investigated AW434047, one of the sequences that was upregulated in carcinomas. The investigation led to the identification of a novel gene, which the authors named hepatocyte malignant transforming factor (HMTF), of unknown function whose expression was increased in hepatocellular carcinomas. Northern blot and in situ hybridization also demonstrated high levels of HMTF in rat hepatocellular carcinoma (HCC) cell lines, lymphocytes in the spleen, colon mucosal epithelia, spermatocytes, and granule cells of the hippocampus. Reduction of HMTF by RNA interference (RNAi) in N1 cells, an HCC cell line, caused suppression of cell proliferation, invasion, and migration. Suppression of proliferation ...
The NPDGamma Experiment measures the parity-violating correlation A{sub {Gamma}Y} between neutron spin and photon momentum in the reaction {rvec n} + p {yields} d + {gamma}. Knowledge of A{sub {Gamma}Y} and other parity-violating observables in few-body nuclear systems will provide constraints for a parameterized description of {Delta}S = 0 parity-violating phenomena free from complications of nuclear structure. The NPDGamma experiment uses a polarized cold pulsed neutron beam, a liquid parahydrogen target, and a cylindrical array of 48 CsI(Tl) scintillation detectors operated in current mode to search for the asymmetry. NPDGamma recently completed the first phase of the program to measure A{sub {Gamma}Y} at the Los Alamos Neutron Science Center with the preliminary result A{sub {Gamma}Y} = (-1.2 {+-} 2.1(stat.) {+-} 0.1(sys.)) x 10{sup -7}, reproducing the previous upper limit from a measurement at a reactor facility. We discuss the theoretical background and ...
A measurement of the t{bar t} production cross section at {radical}s = 1.96 TeV in the dilepton final states using a lepton+track selection and secondary vertex b-tagging is presented. One of the two leptons from the decay of the t{bar t} pair is allowed to be identified only as an isolated track to improve the selection efficiency. The result is combined with a measurement in the t{bar t} {yields} e{mu} final state. The measurements are based on 370 pb{sup -1} of data collected with the D0 experiment at the Tevatron collider. The preliminary cross section obtained in the combined lepton+track and e{mu} channel is: {sigma}{sub t{bar t}} = 8.6{sub -1.7}{sup +1.9}(stat) {+-} 1.1(syst) {+-} 0.6(lumi) pb.
n an early approach, we proposed a kinetic model with multiple translational temperature [K. Xu, H. Liu and J. Jiang, Phys. Fluids {\\bf 19}, 016101 (2007)], to simulate non-equilibrium flows. In this paper, instead of using three temperatures in $x-$, $y-$, and $z$-directions, we are going to further define the translational temperature as a second-order symmetric tensor. Based on a multiple stage BGK-type collision model and the Chapman-Enskog expansion, the corresponding macroscopic gas dynamics equations in three-dimensional space will be derived. The zeroth-order expansion gives the 10 moment closure equations of Levermore [C.D. Levermore, J. Stat. Phys {\\bf 83}, pp.1021 (1996)]. To the 1st-order expansion, the derived gas dynamic equations can be considered as a regularization of Levermore's 10 moments equations. The new gas dynamic equations have the same structure as the Navier-Stokes equations, but the stress strain relationship in the Navier-Stokes ...
Summary Background Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein 96)-peptide complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma. Methods In this open-label trial, patients were randomly assigned to receive either vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation was done in a one to one ratio by a computer-generated pseudo-random number generator, with a block size of four, and was stratified by performance score, lymph node stat...
The $\\bar{K}N$ system at threshold is a sensitive testing ground for low energy QCD, especially for the explicit chiral symmetry breaking. Therefore, we have measured the $K$-series x rays of kaonic hydrogen atoms at the DA$\\Phi$NE electron-positron collider of Laboratori Nazionali di Frascati, and have determined the most precise values of the strong-interaction energy-level shift and width of the $1s$ atomic state. As x-ray detectors, we used large-area silicon drift detectors having excellent energy and timing resolution, which were developed especially for the SIDDHARTA experiment. The shift and width were determined to be $\\epsilon_{1s} = -283 \\pm 36 \\pm 6 {(syst)}$ eV and $\\Gamma_{1s} = 541 \\pm 89 {(stat)} \\pm 22 {(syst)}$ eV, respectively. The new values will provide vital constraints on the theoretical description of the low-energy $\\bar{K}N$ interaction.
1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors ...
Efforts to assess and quantify deleterious effects from toxicants concentrate mainly on single agents whereas real world environmental and occupational exposures to natural and anthropogenic agents entail quite often the concomitant presence of several toxicants. For occupational important exposure situations, combined exposures to physical and chemical agents such as radon and smoking or asbestos and smoking, respectively, were shown to produce over-additive effects at exposure levels typical for earlier workplaces. Already the elucidation of possible health risks from a single agents, its dependence on exposure level, exposure rates, age at exposure and its expression in time is a complex endeavour. Therefore in the past and the present the main emphasis in radiation protection, toxicology, and public health is on the study and assessment of single toxicants. The existing data base on combined effect is rudimentary, mainly descriptive and rarely covers exposure ranges large enough to ...
In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not necessarily evoke the ...
In this thesis, the potential to discover supersymmetric signatures in both e"+e"- and #gamma##gamma# colliders evaluated with a Monte Carlo analysis, is discussed. The analysis was focused on the detection of muons, essentially. First, we study the detection of #mu#"+_R#mu#"-_R in e"-e"+ collisions, whose purpose is the measurement of the #mu#_R mass. It was found that an uncertainty of 0.11 GeV (stat) can be achieved. Under the assumption of the real conditions of the ILC photon collider, a study covering the detection of #mu#"+_R#mu#"-_R and #mu#"+_L#mu#"-_L pairs for #sq root#(s_e_"-_e_"+)=0.5 and 0.6 TeV was performed. According to the simulation, a statistical error for the branching ratios of #mu#"#+-#_L#->##chi#"0_1#mu#"#+-# of 0.98% and #mu#"#+-#_L#->##chi#"0_2#mu#"#+-# of 3.97% can be reached. In order to judge the Monte Carlo results, we have used a technique based on a multidimensional fit to evaluate the impact of the branching ratio measurements ...
The authors report the observation of B{sub s}{sup 0}-{bar B}{sub s}{sup 0} oscillations from a time-dependent measurement of the B{sub s}{sup 0}-{bar B}{sub s}{sup 0} oscillation frequency {Delta}m{sub s}. Using a data sample of 1 fb{sup -1} of p{bar p} collisions at {radical}s = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron, they find signals of 5600 fully reconstructed hadronic B{sub s} decays, 3100 partially reconstructed hadronic B{sub s} decays, and 61,500 partially reconstructed semileptonic B{sub s} decays. They measure the probability as a function of proper decay time that the B{sub s} decays with the same, or opposite, flavor as the flavor at production, and they find a signal for B{sub s}{sup 0}-{bar B}{sub s}{sup 0} oscillations. The probability that random fluctuations could produce a comparable signal is 8 x 10{sup -8}, which exceeds 5{sigma} significance. They measure {Delta}m{sub s} = 17.77 {+-} 0.10(stat) {+-} 0.07(syst) ...
There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries generated by a number of these protocols. Our programmes suggested some empirical guidelines for library design; however, no information was provided regarding library diversity at the protein (rather than DNA) level. We have now updated our web server, enabling analysis of translated libraries constructed by site-saturation mutagenesis and error-prone PCR (epPCR). We introduce GLUE-Including Translation (GLUE-IT), which finds the expected amino acid completeness of libraries in which up to six codons have been independently varied (according to any user-specified randomization scheme). We provide two tools for assisting with experimental design: CodonCalculator, for assessing amino acids corresponding to given randomized codons; and AA-Calculator, for finding degenerate codons that ...
We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ...
In acute liver failure following hepatitis, toxic insults, or after major liver surgery, there is an increased bacterial translocation from the gut. This may explain some of the infectious complications seen in these conditions. To elucidate mechanisms and find possible preventive measures, we investigated the effect of rectal administration of arginine and probiotic bacteria (Lactobacillus spp.) on bacterial translocation and the extent of liver failure. Sprague-Dawley rats were used and five different Lactobacillus strains (Lb. reuteri R2LC, Lb. rhamnosus DSM 6594 (= strain 271), Lb. plantarum DSM 9843 (= strain 299v), Lb. fermentum 8704:3 (= strain 245), and Lb. reuteri (= strain 108) were administered rectally once daily for 8 days with and without 2% arginine. Acute liver injury (ALI) was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples were collected after 24 and 48 hours. Bacterial translocation was evaluated by ...
Several components of high-temperature reactor units have roller bearings in order to carry out their motions without much friction. The use of such bearings poses friction and wear problems which cannot be mastered by commercial roller bearing technology. Possible improvements of coating, cage design and bearing materials as well as of their parameters were registered and studied. The service life of dry lubricated bearings was considerably improved. With a radial or axial load on the bearing of {>=} 10% of the static load, {approx_equal} 20x10{sup 6} rolling motions/actuations can be performed. The connections between surface compression and wear were determined, and optimum conditions for the transfer of lubricants from the cage onto the bearing race were worked out. Coating of corrosion-resistant roller bearing steels with the HRB-M{sub 0}S{sub 2} running-in coating could be proved. New cage designs and materials were tested with positive results. Alternative coatings (thin ...