Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

SHANK3 controls maturation of social reward circuits in the VTA.

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy

Mineralogical and geochemical analysis of Fe-phases in drill-cores from the Triassic Stuttgart Formation at Ketzin CO₂ storage site before CO₂ arrival

Reactive iron (Fe) oxides and sheet silicate-bound Fe in reservoir rocks may affect the subsurface storage of CO2 through several processes by changing the capacity to buffer the acidification by CO2 and the permeability of the reservoir rock: (1) the reduction of three-valent Fe in anoxic environments can lead to an increase in pH, (2) under sulphidic conditions, Fe may drive sulphur cycling and lead to the formation of pyrite, and (3) the leaching of Fe from sheet silicates may affect silicate diagenesis. In order to evaluate the importance of Fe-reduction on the CO2 reservoir, we analysed the Fe geochemistry in drill-cores from the Triassic Stuttgart Formation (Schilfsandstein) recovered from the monitoring well at the CO2 test injection site near Ketzin, Germany. The reservoir rock is a porous, poorly to moderately cohesive fluvial sandstone containing up to 2–4 wt% reactive Fe. Based on a sequential extraction, most Fe falls into the dithionite-extractable Fe-fraction and Fe bound to sheet silicates, whereby some Fe in the dithionite-extractable Fe-fraction may have been leached from illite and smectite. Illite and smectite were detected in core samples by X-ray diffraction and confirmed as the main Fe-containing mineral phases by X-ray absorption spectroscopy. Chlorite is also present, but likely does not contribute much to the high amount of Fe in the silicate-bound fraction. The organic carbon content of the reservoir rock is extremely low (<0.3 wt%), thus likely limiting microbial Fe-reduction or sulphate reduction despite relatively high concentrations of reactive Fe-mineral phases in the reservoir rock and sulphate in the reservoir fluid. Both processes could, however, be fuelled by organic matter that is mobilized by the flow of supercritical CO2 or introduced with the drilling fluid. Over long time periods, a potential way of liberating additional reactive Fe could occur through weathering of silicates due to acidification by CO2

Plant cell culture technology in the cosmetics and food industries : current state and future trends

The production of drugs, cosmetics, and food which are derived from plant cell and tissue cultures has a long tradition. The emerging trend of manufacturing cosmetics and food products in a natural and sustainable manner has brought a new wave in plant cell culture technology over the past 10 years. More than 50 products based on extracts from plant cell cultures have made their way into the cosmetics industry during this time, whereby the majority is produced with plant cell suspension cultures. In addition, the first plant cell culture-based food supplement ingredients, such as Echigena Plus and Teoside 10, are now produced at production scale. In this mini review, we discuss the reasons for and the characteristics as well as the challenges of plant cell culture-based productions for the cosmetics and food industries. It focuses on the current state of the art in this field. In addition, two examples of the latest developments in plant cell culture-based food production are presented, that is, superfood which boosts health and food that can be produced in the lab or at home

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Search for charged Higgs bosons through the violation of lepton universality in t¯t events using pp collision data at ps = 7 TeV with the ATLAS experiment

In several extensions of the Standard Model, the top quark can decay into a bottom quark and a light charged Higgs boson H+, t → bH+, in addition to the Standard Model decay t → bW. Since W bosons decay to the three lepton generations equally, while H+ may predominantly decay into τν, charged Higgs bosons can be searched for using the violation of lepton universality in top quark decays. The analysis in this paper is based on 4.6 fb−1 of proton-proton collision data at √s = 7 TeV collected by the ATLAS experiment at the Large Hadron Collider. Signatures containing leptons (e or μ) and/or a hadronically decaying τ (τhad) are used. Event yield ratios between e+τhad and e+μ, as well as between μ+τhad and μ+e, final states are measured in the data and compared to predictions from simulations. This ratio-based method reduces the impact of systematic uncertainties in the analysis. No significant deviation from the Standard Model predictions is observed. With the assumption that the branching fraction B(H+ → τν) is 100%, upper limits in the range 3.2%–4.4% can be placed on the branching fraction B(t → bH+) for charged Higgs boson masses mH+ in the range 90–140GeV. After combination with results from a search for charged Higgs bosons in t¯t decays using the τhad+jets final state, upper limits on B(t → bH+) can be set in the range 0.8%–3.4%, for mH+ in the range 90–160GeV

An evoked potential mapping of transcallosal projections in the cat

In ten adult cats anesthetized with ketamine hydrochloride the neocortex was exposed and rectangular pulses (1msec, 0.5 Hz and variable intensity) were applied to discrete points of one side and transcallosal evoked potentials were recorded from the other. The stimulation and recording positions were determined on a cartesian map of most of the exposable neocortical areas and the potentials were analysed as to their components, voltage and latency. Passive spread and electrotonic potentials and the effects of increasing frequency were also analysed. The results showed large transcallosal potentials in some areas and an increase of potentials in the caudorostral direction, attaining the highest values in anteromedial areas of the suprasylvian gyrus. Confirming anatomical studies, a few silent spots were found in the motor and somesthetic cortex and in restricted posterior regions of the visual cortex, where small or zero voltages occurred. While causing weak contralateral potentials, stimulation of some posterior sites provoked high voltage potentials in anterior regions of the side being stimulated and in the corresponding area of the opposite site. These posterior sites are. poorly interconnected by the corpus callosum. The L-shaped indirect connection described in this work may be involved in some types of epilepsy and may explain the effectiveness of partial callosotomy in their treatment

Bayesian Based Comment Spam Defending Tool

Spam messes up user's inbox, consumes network resources and spread worms and viruses. Spam is flooding of unsolicited, unwanted e mail. Spam in blogs is called blog spam or comment spam.It is done by posting comments or flooding spams to the services such as blogs, forums,news,email archives and guestbooks. Blog spams generally appears on guestbooks or comment pages where spammers fill a comment box with spam words. In addition to wasting user's time with unwanted comments, spam also consumes a lot of bandwidth. In this paper, we propose a software tool to prevent such blog spams by using Bayesian Algorithm based technique. It is derived from Bayes' Theorem. It gives an output which has a probability that any comment is spam, given that it has certain words in it. With using our past entries and a comment entry, this value is obtained and compared with a threshold value to find if it exceeds the threshold value or not. By using this concept, we developed a software tool to block comment spam. The experimental results show that the Bayesian based tool is working well. This paper has the major findings and their significance of blog spam filter.Comment: 14 Pages,4 Figures, International Journal of Network Security & Its Applications (IJNSA), Vol.2, No.4, October 201