Schizophrenia gene expression profile reverted to normal levels by antipsychotics

BACKGROUND: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. METHODS: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. RESULTS: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics. CONCLUSIONS: These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs

A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector

A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fb−1 − 1 of √ s = 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, ̃ t ~ , which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV<̃<410 100 GeV < m t ~ < 410 GeV GeV are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV<̃<470 100 GeV < m t ~ < 470 GeV GeV and 480 GeV<̃<610 480 GeV < m t ~ < 610 GeV GeV . Additional limits are set on the pair-production of massive colour-octet resonances

Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

The rejection of forward jets originating from additional proton–proton interactions (pile-up) is crucial for a variety of physics analyses at the LHC, including Standard Model measurements and searches for physics beyond the Standard Model. The identification of such jets is challenging due to the lack of track and vertex information in the pseudorapidity range |η| &gt; 2.5. This paper presents a novel strategy for forward pile-up jet tagging that exploits jet shapes and topological jet correlations in pile-up interactions. Measurements of the per-jet tagging efficiency are presented using a data set of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV collected with the ATLAS detector. The fraction of pile-up jets rejected in the range 2.5 &lt; |η| &lt; 4.5 is estimated in simulated events with an average of 22 interactions per bunch-crossing. It increases with jet transverse momentum and, for jets with transverse momentum between 20 and 50 GeV, it ranges between 49% and 67% with an efficiency of 85% for selecting hard-scatter jets. A case study is performed in Higgs boson production via the vector-boson fusion process, showing that these techniques mitigate the background growth due to additional proton–proton interactions, thus enhancing the reach for such signatures

Multiple-peak switching current distribution in Tl-Ba-Ca-Cu-O intrinsic Josephson junctions

We have fabricated series arrays of intrinsic Josephson junctions of area (2 mum)(2) in thin films of Tl2BaCaCu2O8 grown on vicinal substrates. Measurements of the distribution of the bias current at which a voltage first appears across the array show two peaks in the temperature range between 14 and 20 K. Fitting the data to a simple thermal activation model for a small Josephson junction shows that these peaks correspond to phase-locked switching of two or three junctions respectively. Below 14 K the distribution broadens significantly which we attribute to a crossover to long-junction behaviour. Intrinsic junctions of smaller area (0.5 x 0.7 mum(2)) display no such fluctuations down to 4.2 K, confirming this interpretation. (C) 2002 Elsevier Science B.V. All rights reserved

In-plane magnetic field dependence of intrinsic Josephson junctions in Tl-Ba-Ca-Cu-O thin films

We have fabricated intrinsic Josephson bridges using Tl-Ba-Ca-Cu-O thin films grown on vicinal lanthanum aluminate substrates, Measurements of the lock-in transition allow us align a magnetic field of up to 4T with the copper oxide planes to better than 0.3 degrees. This allows us to study the dynamics of Josephson fluxons in the films, For fields above 1.4T and at low currents we observe Josephson flux creep. Above a field-dependent threshold current we observe free flow of the fluxons with a flux-flow resistance which is proportional to field. The fluxons reach a field-independent velocity before the jump to the quasiparticle branch occurs. Our results suggest that the development of a sub-mm-wave oscillator using these bridges will require sub-micron patterning

Josephson effects in misaligned Tl-2212 films

We have measured Josephson RSJ-like static current-voltage characteristics in 2-mu m-wide bridges patterned in the [cos 20 degrees 0 sin 20 degrees] direction in 200 degrees misaligned thin films of Tl2Ba2CaCu2O8 grown on vicinal LaAlO3 substrates. The temperature dependence of the critical current of the bridge is well-described by Josephson SIS tunnelling between two BCS superconductors, with IcRn equal to 26 mV at 4.4 K. Conversely, the current-voltage characteristics of bridges patterned in the orthogonal [0 1 0] direction in the same films show flux-flow behaviour. This, coupled with the insensitivity of the inter-plane critical current to a small magnetic field, strongly suggests that the Josephson behaviour we have observed is due to intrinsic Josephson coupling between adjacent copper oxide planes, and not to extrinsic inter-grain coupling. (C) 1999 Elsevier Science B.V. All rights reserved

Properties of Tl2Ba2CaCu2O8 thin film intrinsic Josephson junctions in an in-plane magnetic field

We have performed transport measurements on intrinsic Josephson junctions in misaligned thin films of Tl2Ba2CaCu2O8. This has been done in both zero field and in-plane aligned magnetic fields of up to 5 T. We have compared wet-etched and ion-milled devices and find that the more precise structure produced by ion-milling gives superior results. In the case of ion-milled devices we are able to individually switch on up to 50 junctions. For an n-plane field of 3 T there is complete suppression of the critical current. We have seen displaced branches for in-plane fields above 1.5 T. This branching is due to Josephson flux flow. For in-plane fields greater than 2 T the relationship between the maximum flux-flow voltage and the applied field is linear. (C) 2001 Elsevier Science B.V. All rights reserved

Fabrication and measurement of intrinsic Josephson junctions in misaligned films of Tl2Ba2CaCu2O8

Instrinsic Josephson bridges have been patterned in films of Tl2Ba2CaCu2O8. Due to our device geometry we have used films that are misaligned at 20 degrees to the substrate surface. This misalignment has been confirmed using four-circle x-ray diffraction and cross-sectional transmission electron microscopy, Our films still retain a high critical temperature (108K) despite their misalignment, The resistive anisotropy of the film is comparable to single crystal data. The product of the critical current and normal state resistance is equal to 14mV at 4.2K and is independent of the critical current density, These two achievements are attributed to the lack of engineered interfaces in our intrinsic junctions. A run-to-run variation in the critical current is explained by the presence of non-Josephson shunts in the junction, Junctions with fewer non-Josephson shunts show greater hysteresis

Alternating current Josephson effect in intrinsic Josephson bridges in Tl2Ba2CaCu2O8 thin films

We have performed transport measurements on bridges patterned in misaligned thin films of the superconductor Tl2Ba2CaCu2O8. There is a c-axis component of current flow along the bridge, giving rise to hysteretic Josephson-like current-voltage curves. The temperature dependence of the critical current follows the Ambegaokar-Baratoff theory with IcRN up to 26 mV at 4.2 K. Microwave emission from the Josephson junctions near Tc (≈103 K) has been detected using an X-band detector. We show that 700±15 junctions in the bridge are actively oscillating, confirming that the junctions are "intrinsic" junctions formed by adjacent copper oxide planes in the Tl2Ba2CaCu2O8 crystal structure. © 2000 American Institute of Physics

Josephson fluxon flow and phase diffusion in thin-film intrinsic Josephson junctions

The transport properties of intrinsic Josephson junction arrays as a function of both temperature and magnetic field were measured. The magnetic field was applied perpendicular to the transport current. The transport properties were dominated by Josephson vortex flow for widths greater than the Josephson penetration depth and the zero-field dissipation was dominated by Josephson phase diffusion. The results show that in an applied in-plane magnetic field the fluxons are pinned up to a sample-dependent depinning field and the fluxon-flow resistance increases linearly with field