This paper describes the development of an intense positron source with the hybrid target. A series of experiments on positron generation with the hybrid target has been carried out with a 8-GeV electron beam at the KEKB linac. We observed that positron yield from the hybrid target increased when the incident electron MK2206 beam was aligned to the crystal axis and exceeded the one from the conventional target with the converter target of the same thickness, when its thickness is less than about
2 radiation length. The measurements in the temperature rise of the amorphous converter target was successfully carried out by use of thermocouples. These results lead to establishment to the evaluation of the hybrid target as an intense
find more positron source. (C) 2013 Elsevier B.V. All rights reserved.”
“Clovers (Trifolium) may possess a significant therapeutic potential, but the effects of compounds from these plants on blood platelets and haemostasis have been poorly recognized. The present study was designed to evaluate the antioxidative action of extracts from three species of clovers: Trifolium pratense, Trifolium pallidum and Trifolium scabrum in the protection of human blood platelets in vitro. Platelet suspensions were pre-incubated with crude extract and phenolic fraction of T. pratense or phenolic fractions of T. scabrum and T. pallidum, at the final concentrations
of 0.5-50 mu g/ml. Then, for the induction of oxidative stress, 100 mu M peroxynitrite was added. The antioxidative activity of plant extracts was assessed by measurements of the level of 3-nitrotyrosine, thiol groups and lipid peroxidation products (hydroperoxides and thiobarbituric acid-reactive substances). Despite the significant differences in the composition of the investigated extracts, we observed antioxidative effects of all used mixtures. The presence of Trifolium extracts considerably see more reduced the peroxynitrite-mediated modifications of proteins and diminished peroxidation of lipids in platelets. Our results indicate on a strong antioxidative activity of the tested extracts-statistically significant effects were found even for the lowest concentrations (0.5 mu g/ml) of all extracts. This action may be useful in the protection of blood components, very susceptible to oxidative modifications. The obtained results suggest that the examined clovers are a promising source of compounds, valuable for the protection against oxidative stress-induced damage to blood platelets.”
“The surface layer of the oceans and other aquatic environments contains many bacteria that range in activity, from dormant cells to those with high rates of metabolism. However, little experimental evidence exists about the activity of specific bacterial taxa, especially rare ones.
Glutamate receptors therefore represent exciting targets for the development of novel pharmacological therapies for PD.”
“The GABARAPL1 (GABARAP-LIKE 1) gene was first described
as an early estrogen-regulated gene that shares a high sequence homology with GABARAP and is thus a part of the GABARAP family. GABARAPL1, like GABARAP, interacts with the GABA A receptor and tubulin and promotes tubulin polymerization. The GABARAP family members (GABARAP, GABARAPL1 and GABARAPL2) and their close homologs (LC3 and Atg8) are not only involved in the transport of proteins or vesicles but are also implicated in various mechanisms such as autophagy, cell death, cell proliferation and tumor progression. However, despite these similarities, GABARAPL1 displays a complex regulation that is different from that Selleck BTSA1 of other GABARAP family members. Moreover, it presents a regulated tissue expression and is the most highly expressed gene among the family in the central nervous system. In this review article, we will outline the specific functions of this protein and also hypothesize about the roles that GABARAPL1 might have in several important biological processes such as cancer or neurodegenerative diseases.”
“Background: Metabolic syndrome (MetS) is associated with an increased risk of the development of atherosclerotic cardiovascular disease (CVD). Interleukin-18 (IL-18), which
is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response system, plays a crucial role selleck compound in vascular pathologies. IL-18 is also a predictor of cardiovascular death in patients with CVD and is involved in atherosclerotic plaque destabilization.\n\nResults:
In order to determine if circulating levels of IL-18 can serve as a specific biomarker for distinguishing MetS patients from pre-MetS subjects, we studied 78 patients with visceral fat deposition and 14 age-matched control subjects. Increased levels of IL-18 were observed more frequently in patients with MetS than in pre-MetS subjects and were positively associated with waist circumference. Serum levels of IL-18 were significantly reduced by a change in weight caused by lifestyle modifications. There was a significant interaction between waist circumference and serum IL-18 concentration. buy EVP4593 Weight loss of at least 5% of the body weight caused by lifestyle modification decreased IL-18 circulating levels relative to the reduction in waist circumference and blood pressure, suggesting that this degree of weight loss benefits the cardiovascular system.\n\nConclusion: IL-18 may be a useful biomarker of the clinical manifestations of MetS and for the management of the risk factors of CVD.”
“Background: The accurate diagnosis of dysplasia or carcinoma within ampullary lesions can be difficult, but, when possible, identifies patients who require endoscopic or surgical resection, respectively.
38 +/- 0.03 vs 0.67 +/- 0.05, P < .05). Preincubation with CXCR4-Ab, AMD3100, or LY294002 significantly attenuated the enhanced in vitro and in vivo effects of Foxc2-EPCs.\n\nConclusions: Our findings indicate that Foxc2 overexpression increases CXCR4 expression of EPCs and efficiently enhances the homing potential of EPCs, thereby improving EPCs-mediated therapeutic benefit after endothelial injury. Foxc2 may be a novel molecular target for
improving the therapeutic efficacy of EPCs transplantation. (J Vase Surg 2011;53:1668-78.)”
“MicroRNA alterations and axonopathy have been reported in patients with Alzheimer’s disease (AD) and in AD mouse models. We now report that miR-342-5p is upregulated in APP/PS1, PS1 Delta E9, and PS1-M146V transgenic AD mice, and that this upregulation is mechanistically linked to elevated BAY 80-6946 beta-catenin, c-Myc, and interferon regulatory factor-9. The increased miR-342-5p downregulates
the expression of ankyrin G (AnkG), a protein that is known to play a critical role at the axon initial segment. Thus, a specific miRNA alteration may contribute to AD axonopathy by downregulating AnkG.”
“Spatial and temporal isolation and environmental variability are important factors explaining variation in plant species composition. The effect of fragmentation and disturbance on woody plant species composition was studied using data from 32 remnant church forest patches in northern Ethiopia. The church forests
are remnants of dry Afromontane forest, selleck screening library https://www.selleckchem.com/products/gant61.html embedded in a matrix of intensively used crop and grazing lands. We used canonical correspondence analysis and partial canonical correspondence analysis to analyze the effects of fragmented and isolated forest-patch identity, environmental and spatial variables on woody plant species composition in different growth stages. The dominance of late successional species was higher at the adult growth stage than seedlings and saplings growth stages. In the adult stages, late successional species like Olea europaea subsp. cuspidate had high frequency of occurrence. Forest patch identity was more important in explaining woody plant assemblages than environmental and spatial variables. For all growth stages combined, environmental variables explained more of the explained total fraction of variation in species composition than spatial variables. Topographic variables best explained variations in species composition for saplings, adults and all growth stages combined, whereas the management regime was most important for seedlings species composition. Our results show that in a matrix of cultivated and grazing land, fragmented and isolated forest patches differ in woody plant species assemblages. Some species are widely distributed and occurred in many patches while other occurred only in one or a few forest patches.
Here, we focus on the problem of conformational sampling. The current state of the art solution is based on fragment assembly methods, which construct plausible conformations by stringing together short fragments obtained from experimental structures. However, the discrete nature of the fragments necessitates the use of carefully tuned, unphysical energy functions, and their
non-probabilistic nature impairs unbiased sampling. We offer a solution to the sampling problem that removes these important limitations: a probabilistic model of RNA structure that allows efficient sampling of RNA conformations in continuous space, and with associated probabilities. We show that the model captures several key LY2090314 features of RNA structure, such as its rotameric nature and the distribution of the helix lengths. Furthermore, the model readily generates native-like 3-D conformations for 9 out of 10 test structures, solely using coarse-grained base-pairing information. In conclusion, the method provides a theoretical and practical Bioactive Compound Library supplier solution for a major bottleneck on the way to routine prediction and simulation of RNA structure and dynamics in atomic detail.”
Myocardial infarct heterogeneity indices including peri-infarct gray zone are predictors for spontaneous ventricular arrhythmias events after ICD implantation in patients with ischemic heart disease. In this study we hypothesize that the extent of peri-infarct gray zone and papillary muscle infarct scores determined by a new multi-contrast late enhancement (MCLE) method may predict appropriate ICD therapy in patients with ischemic heart disease.\n\nMethods: The cardiovascular magnetic resonance (CMR) protocol included LV functional parameter assessment and late gadolinium enhancement (LGE) CMR using the conventional method and MCLE post-contrast. The proportion of
peri-infarct gray zone, core infarct, total infarct relative to LV myocardium mass, papillary muscle infarct scores, and LV functional parameters were statistically compared between groups with and without appropriate ICD therapy during follow-up.\n\nResults: ACY-738 order Twenty-five patients with prior myocardial infarct for planned ICD implantation (age 64 +/- 10 yrs, 88% men, average LVEF 26.2 +/- 10.4%) were enrolled. All patients completed the CMR protocol and 6-46 months follow-up at the ICD clinic. Twelve patients had at least one appropriate ICD therapy for ventricular arrhythmias at follow-up. Only the proportion of gray zone measured with MCLE and papillary muscle infarct scores demonstrated a statistically significant difference (P < 0.05) between patients with and without appropriate ICD therapy for ventricular arrhythmias; other CMR derived parameters such as LVEF, core infarct and total infarct did not show a statistically significant difference between these two groups.
These different environments are modeled by a unique “water” scaling factor that decreases or
increases the strength of hydrogen bonds depending on whether water contacts the acceptor or donor atoms or the bond is fully desolvated, respectively. Our empirical energies are fully consistent with mobile water molecules having a strong polarization effect in direct intermolecular interactions. Proteins 2010; 78:3226-3234. (C) 2010 Wiley-Liss, Inc.”
“Tuberculosis this website (113) is an important public health problem in Nepal. The aim of this study was to investigate the spatial and temporal variations in TB incidence in Nepal. Data regarding TB cases were obtained from the Nepal National Tuberculosis Center (NTC) for 2003-2010
and analyzed. Models were developed for TB incidence by gender, year and location using linear regression of log-transformed incidence rates. Apart from a relatively small number of outliers, these models provided a good fit, as indicated by residual plots and the r-squared statistic (0.94). The overall incidence of TB was 1.31 cases per 1,000 population with a male to female incidence rate ratio of 1.83. There were trends of increasing FG-4592 order incidence in TB for recent years among both sexes. There were marked variations by location with higher rates occurring in the Terai region and relatively moderate and low rates of TB in the Hill and Mountain regions, respectively. TB incidence was also higher in the capital city Kathmandu and other metropolitan Selleck BEZ235 cities. A log-linear regression model can be used as a simple method to model TB incidence rates that vary by location and year. These findings provide information for health authorities to help establish effective prevention programs in specific areas where the disease burden is relatively high.”
“Hot wire chemical vapor deposition (HWCVD), also referred
to as catalytic CVD (Cat-CVD), has been used to produce Si-containing thin films, nanomaterials, and functional polymer coatings that have found wide applications in microelectronic and photovoltaic devices, in automobiles, and in biotechnology. The success of HWCVD is largely due to its various advantages, including high deposition rate, low substrate temperatures, lack of plasma-induced damage, and large-area uniformity. Film growth in HWCVD is induced by reactive species generated from primary decomposition on the metal wire or from secondary reactions in the gas phase. In order to achieve a rational and efficient optimization of the process, it is essential to identify the reactive species and to understand the chemical kinetics that govern the production of these precursor species for film growth. In this Account, we report recent progress in unraveling the complex gas-phase reaction chemistry in the HWCVD growth of silicon carbide thin films using organosilicon compounds as single-source precursors.
The multiphoton fluorescence technology perceived the tissue-covered subgingival calculus that cannot be observed by the
one-photon confocal fluorescence method. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3593150]“
“During wakefulness, pyramidal neurons in the intact brain are bombarded by synaptic input that causes tonic depolarization, increased membrane KU-57788 chemical structure conductance (i.e., shunting), and noisy fluctuations in membrane potential; by comparison, pyramidal neurons in acute slices typically experience little background input. Such differences in operating conditions can compromise extrapolation of in vitro data to explain neuronal operation in vivo. For instance, pyramidal neurons have been identified as integrators (i. e., class 1 neurons according to Hodgkin’s classification of intrinsic excitability) based on in vitro experiments but that classification is inconsistent MEK inhibition with the ability
of hippocampal pyramidal neurons to oscillate/resonate at theta frequency since intrinsic oscillatory behavior is limited to class 2 neurons. Using long depolarizing stimuli and dynamic clamp to reproduce in vivo-like conditions in slice experiments, we show that CA1 hippocampal pyramidal cells switch from integrators to resonators, i. e., from class 1 to class 2 excitability. The switch is explained by increased outward current contributed by the M-type potassium current I(M), which shifts the balance of inward
and outward currents active at perithreshold potentials and thereby converts the spike-initiating mechanism as predicted by dynamical analysis of our computational model. Perithreshold activation of I(M) is enhanced by the depolarizing shift in spike threshold caused by shunting and/or sodium channel inactivation secondary to tonic depolarization. Our conclusions were validated by multiple comparisons between simulation and experimental data. Thus even so-called “intrinsic” properties may differ qualitatively between in vitro and in vivo conditions.”
“A OICR-9429 coarse-grained molecular model, which consists of a spherical particle and an orientation vector, is proposed to simulate lipid membrane on a large length scale. The solvent is implicitly represented by an effective attractive interaction between particles. A bilayer structure is formed by orientation-dependent (tilt and bending) potentials. In this model, the membrane properties (bending rigidity, line tension of membrane edge, area compression modulus, lateral diffusion coefficient, and flip-flop rate) can be varied over broad ranges. The stability of the bilayer membrane is investigated via droplet-vesicle transition. The rupture of the bilayer and worm-like micelle formation can be induced by an increase in the spontaneous curvature of the monolayer membrane. (C) 2011 American Institute of Physics. [doi: 10.1063/1.
Using a mouse model of breast cancer,
we tested the importance of the senescence response in solid cancer and identified genetic pathways regulating this response. Mammary expression of activated Ras led to the formation of senescent cellular foci in a majority of mice. Deletion of the p19(ARF), p53, or p21(WAF1) tumor suppressors but not p16(lNK4a) prevented senescence and permitted tumorigenesis. Id1 has been implicated in the control of senescence in vitro, and elevated expression of Id1 is found in a number of solid cancers, so we tested whether overexpression of Id1 regulates senescence in vivo. Although overexpression of Id1 in the mammary epithelium was not sufficient for tumorigenesis, mice with expression of both Id1 and activated Ras developed metastatic cancer. These tumors expressed high levels of p(19Arf), GDC-0941 in vivo p53, and p21(Waf1), demonstrating that Id1 acts find more to make cells refractory to p21(Waf1)-dependent cell cycle arrest. Inactivation of the conditional Id1 allele in established tumors led to widespread senescence
within 10 days, tumor growth arrest, and tumor regression in 40% of mice. Mice in which Id1 expression was inactivated also exhibited greatly reduced pulmonary metastatic load. These data demonstrate that established tumors remain sensitive to senescence and that Id1 may be a valuable target for therapy.”
“We report a new strategy towards the control of carbon nanotube (CNT) structure and continuous fibre formation using a floating catalyst direct spinning CVD process. Combretastatin A4 purchase In the procedures used to date, a sulphur promoter
precursor is added to significantly enhance the rate of CNT formation in the floating catalyst synthesis. Within the reaction zone, the rapidly grown nanotubes self-assemble into bundles, followed by their continuous spinning into fibres, yarns, films or tapes. In this paper we demonstrate a catalyst control strategy in the floating catalyst system, where the CNT formation process is independent of the presence of a promoter but leads to successful spinning of the macroscopic carbon nanotube assemblies with specific morphology, high purity (Raman D/G 0.03) and very narrow diameter range (0.8-2.5 nm). This can be achieved by the control of catalyst precursor decomposition and subsequent formation of homogeneous nano-sized catalyst particles.”
“To investigate the hyphal-form transition of Trichosporon asahii (T. asahii) of different sources under different temperatures, media and cultural times; eleven T. asahii strains were isolated and maintained in RPMI-1640 medium, YPD liquid medium, Tween yeast bouillon (TYB) medium and 50% (v/v) fetal calf serum (FBS) medium independently to induce the hyphal growth. Culture was performed at 15, 25 and 37 degrees C for 1, 2, 3, 6, 12 and 24 h and the hyphal formation (growth) rate was calculated. The mean hyphal formation rate was (0.15 +/- 0.42)% at 15, (5.75 +/- 3.48)% at 25 degrees C and (33.81 +/- 15.39)% at 37 degrees C (P<0.
This study provides evidence to support the use of 3D multi-shot acquisition sequences in lieu of single-shot EPI for ultra high field BOLD fMRI at 7 T. (C) 2011 Elsevier Inc. All rights
“Purpose of review\n\nThe prevalence of atrial fibrillation is increasing because of an aging population. Vitamin K antagonists have been the standard therapy for stroke prevention in atrial fibrillation but are underutilized Selleckchem C59 wnt and often poorly managed because of their inherent limitations. This study critically reviews the recently completed phase 3 randomized controlled trials of new oral anticoagulants (OACs) for stroke prevention in patients with nonvalvular atrial fibrillation: RE-LY (dabigatran), AVERROES (apixaban), ARISTOTLE (apixaban) and ROCKET-AF (rivaroxaban).\n\nRecent findings\n\nOn the basis of their favorable pharmacological characteristics and excellent efficacy and safety profile as demonstrated by the results of the randomized controlled trials, the new OACs have the potential to replace vitamin K antagonists as the first-line treatment for LY2603618 order stroke prevention in atrial fibrillation, with warfarin reserved for patients
with contraindications to the new OACs and those unable to afford them.\n\nSummary\n\nThe new OACs represent a major advance for patients with atrial fibrillation with the potential to reduce morbidity and mortality due to cardioembolic stroke.”
“Oil-bee/oil-flower mutualism evolved through multiple gains and H 89 order losses of the ability to produce floral oil in plants and
to collect it in bees. Around 2000 plant species are known to produce floral oils that are collected by roughly ’450 bee species, which use them for the construction of nests and for the larval food. The Plantaginaceae contain several Neotropical species that produce floral oils, the main reward offered by these plants. In the genera Angelonia, Basistemon, Monopera and Monttea, mainly associated with Centris bees, the floral oil is produced in trichomes that are located in the inner corolla. The pollinators of a few species in this neotropical clade of Plantaginaceae are known, and the role of flower morphology as well as the requirements from pollinators and the role of other groups of bees in the pollination of these flowers remains unclear. In this paper we provide a list of the flower visitors of seven Plantaginaceae species (six Angelonia species and Basistemon silvaticus) analyzing their behavior to highlight the legitimate pollinators and illustrating little known aspects of flower morphology and oil-collecting apparatuses of the bees. Two general morphological patterns were observed in the Angelonia flowers: deep corolla tube with short lobes, and short corolla tube with long lobes. Corolla tubes of different length result in pollen adherence to different parts of the insect body. The six Angelonia species and B.
\n\nThe optical characteristics of these pyramids depend on particle orientation, wavevector direction, and polarization direction and can be tuned. Using the multipolar surface plasmon resonances of large (> 250 nm) pyramids, imaging and spectral identification
of pyramid orientation in condensed media was possible. We were also able to direct pyramids to assemble into one- and two-dimensional arrays with interesting optical properties. Furthermore, modification of the PEEL fabrication scheme allowed the production of multimaterial pyramidal structures KU-57788 clinical trial with complex attributes, highlighting the power of this platform for exacting nanometer-scale control over particle structure and composition.”
“Purpose SN 28049 (N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide) is
a DNA intercalating drug that binds selectively to GC-rich DNA and shows curative activity against the Colon 38 adenocarcinoma in mice. We wished to investigate the roles of topoisomerase (topo) I, topo II and RNA transcription in the action of SN 28049.\n\nMethods We used clonogenic assays to study the cytotoxicity of SN 28049; RNA interference and enzyme assays to examine the role of topo I in SN 28049 action; (3)H uridine incorporation and reporter assays to study its effects on transcription; and RT-PCR to examine its ability to reduce endogenous h-TERT expression.\n\nResults In clonogenic assays, SN 28049 showed a biphasic cytotoxic dose response curve in H460 cells typical of MEK pathway acridine derivatives OICR-9429 ic50 such as N-[2-(dimethylamino)ethylacridine-4-carboxamide (DACA) although it was similar to 16-fold more potent. Down-regulation of topo II alpha in HTETOP cells reduced the cytotoxicity of SN 28049, establishing its action as a topo II alpha poison. Surprisingly, down-regulation of topo I in H460 cells by RNA interference sensitised them to the actions of SN 28049 and other topo II poisons. SN 28049 also inhibited topo I-mediated relaxation
of supercoiled plasmid DNA. SN 28049 was also an inhibitor of transcription in HEK293 cells and was more potent at reducing luciferase expression from a GC-rich SP-1 binding promoter than from a non-GC-rich AP-1 binding promoter. The drug also reduced luciferase reporter gene expression driven by the SP-1-binding survivin promoter as well as reducing endogenous h-TERT expression in HEK293 cells whose promoter also contains SP-1 binding sites.\n\nConclusion We conclude that SN 28049 has a complex action that may involve poisoning of topo II alpha, suppression of topo I and inhibition of gene transcription from promoters with SP-1 sites. These actions may contribute to the promising experimental solid tumour anticancer activity of SN 28049.
Both mice lack B and T cell functions selleck screening library due to the absence of rag2. Results: Primary tumors developed in 16/16 in pfp/rag2 and 20/20 rag2 mice. At sacrifice primary tumor weight did not differ significantly. However, tumors grew faster in pfp/rag2 mice (50 days) than in pfp/rag2 mice (70 days). Circulating tumor cells (CTC) in murine blood were
nearly three times higher in pfp/rag2 (68 cells/ml) than in rag2 mice (24 cells/ml). Lung metastases occurred frequently in pfp/rag2 mice (13/16) and infrequently in rag2 mice (5/20). The mean number of metastases was 789 in pfp/rag2 mice compared to 210 in rag2 mice. Lung metastases in pfp/rag2 mice consisted of 10-100 tumor cells while those in rag2 mice were generally disseminated tumor cells (DTCs). Computer modelling showed that perforin-dependent killing of NK cells decelerates the growth of the primary tumour and kills 80% of CTCs. Furthermore, perforin-mediated cytotoxicity hampers the proliferation of the malignant cells in host tissue forcing them to stay dormant for at least 30 days. Conclusion: The results exactly quantified the effect of perforin-dependent direct cytotoxicity of NK cells on HT29 on primary tumor growth, number of CTCs in the blood and the number of metastases. The largest effects
were seen in the number of mice developing spontaneous selleck chemical lung metastases and the mean number of lung metastases. Hence, perforin-mediated cytotoxicity used for direct killing by NK cells is more important than indirect killing by secretion of death-inducing
ligands by NK cells.”
“Hexavalent chromium is a human carcinogen activated primarily by direct reduction with cellular ascorbate Quisinostat and to a lesser extent, by glutathione. Cr(III), the final product of Cr(VI) reduction, forms six bonds allowing intermolecular cross-linking. In this work, we investigated the ability of Cr(VI) to cause interstrand DNA cross-links (ICLs) whose formation mechanisms and presence in human cells are currently uncertain. We found that in vitro reduction of Cr(VI) with glutathione showed a sublinear production of ICLs, the yield of which was less than 1% of total Cr-DNA adducts at the optimal conditions. Formation of ICLs in fast ascorbate-Cr(VI) reactions occurred during a short reduction interval and displayed a linear dose dependence with the average yield of 1.3% of total adducts. In vitro production of ICLs was strongly suppressed by increasing buffer molarity, indicating inhibitory effects of ligand-Cr(III) binding on the formation of cross-linking species. The presence of ICLs in human cells was assessed from the impact of ICL repair deficiencies on Cr(VI) responses.