High temperature dielectric ceramics: a review of temperature-stable high-permittivity perovskites

Recent developments are reviewed in the search for dielectric ceramics which can operate at temperatures >200 °C, well above the limit of existing high volumetric efficiency capacitor materials. Compositional systems based on lead-free relaxor dielectrics with mixed cation site occupancy on the perovskite lattice are summarised, and properties compared. As a consequence of increased dielectric peak broadening and shifts to peak temperatures, properties can be engineered such that a plateau in relative permittivity–temperature response (εr–T) is obtained, giving a ±15 %, or better, consistency in εr over a wide temperature range. Materials with extended upper temperature limits of 300, 400 and indeed 500 °C are grouped in this article according to the parent component of the solid solution, for example BaTiO3 and Na0.5Bi0.5TiO3. Challenges are highlighted in achieving a lower working temperature of −55 °C, whilst also extending the upper temperature limit of stable εr to ≥300 °C, and achieving high-permittivity and low values of dielectric loss tangent, tan δ. Summary tables and diagrams are used to help compare values of εr, tan δ, and temperature ranges of stability for different material

Phthiocerol Dimycocerosates of M. tuberculosis Participate in Macrophage Invasion by Inducing Changes in the Organization of Plasma Membrane Lipids

Phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), in particular during the early step of infection when bacilli encounter their host macrophages. However, their cellular and molecular mechanisms of action remain unknown. Using Mtb mutants deleted for genes involved in DIM biosynthesis, we demonstrated that DIM participate both in the receptor-dependent phagocytosis of Mtb and the prevention of phagosomal acidification. The effects of DIM required a state of the membrane fluidity as demonstrated by experiments conducted with cholesterol-depleting drugs that abolished the differences in phagocytosis efficiency and phagosome acidification observed between wild-type and mutant strains. The insertion of a new cholesterol-pyrene probe in living cells demonstrated that the polarity of the membrane hydrophobic core changed upon contact with Mtb whereas the lateral diffusion of cholesterol was unaffected. This effect was dependent on DIM and was consistent with the effect observed following DIM insertion in model membrane. Therefore, we propose that DIM control the invasion of macrophages by Mtb by targeting lipid organisation in the host membrane, thereby modifying its biophysical properties. The DIM-induced changes in lipid ordering favour the efficiency of receptor-mediated phagocytosis of Mtb and contribute to the control of phagosomal pH driving bacilli in a protective niche

A Computational Profiling of Changes in Gene Expression and Transcription Factors Induced by vFLIP K13 in Primary Effusion Lymphoma

Infection with Kaposi's sarcoma associated herpesvirus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), a rare lymphoproliferative disorder that is characterized by loss of expression of most B cell markers and effusions in the body cavities. This unique clinical presentation of PEL has been attributed to their distinctive plasmablastic gene expression profile that shows overexpression of genes involved in inflammation, adhesion and invasion. KSHV-encoded latent protein vFLIP K13 has been previously shown to promote the survival and proliferation of PEL cells. In this study, we employed gene array analysis to characterize the effect of K13 on global gene expression in PEL-derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate that K13 upregulates the expression of a number of NF-κB responsive genes involved in cytokine signaling, cell death, adhesion, inflammation and immune response, including two NF-κB subunits involved in the alternate NF-κB pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes downregulated by K13. A comparison with K13-induced genes in human vascular endothelial cells revealed that although there was a considerable overlap among the genes induced by K13 in the two cell types, chemokines genes were preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which was induced in both cell types. Functional studies confirmed that K13 activated the RANTES/CCL5 promoter through the NF-κB pathway. Taken collectively, our results suggest that K13 may contribute to the unique gene expression profile, immunophenotype and clinical presentation that are characteristics of KSHV-associated PEL

Viral Mimicry of Cdc2/Cyclin-Dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress

The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser22). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser22 is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

TMEM120A and B: Nuclear Envelope Transmembrane Proteins Important for Adipocyte Differentiation

<div><p>Recent work indicates that the nuclear envelope is a major signaling node for the cell that can influence tissue differentiation processes. Here we present two nuclear envelope trans-membrane proteins TMEM120A and TMEM120B that are paralogs encoded by the <i>Tmem120A</i> and <i>Tmem120B</i> genes. The TMEM120 proteins are expressed preferentially in fat and both are induced during 3T3-L1 adipocyte differentiation. Knockdown of one or the other protein altered expression of several genes required for adipocyte differentiation, <i>Gata3</i>, <i>Fasn</i>, <i>Glut4</i>, while knockdown of both together additionally affected <i>Pparg</i> and <i>Adipoq</i>. The double knockdown also increased the strength of effects, reducing for example <i>Glut4</i> levels by 95% compared to control 3T3-L1 cells upon pharmacologically induced differentiation. Accordingly, TMEM120A and B knockdown individually and together impacted on adipocyte differentiation/metabolism as measured by lipid accumulation through binding of Oil Red O and coherent anti-Stokes Raman scattering microscopy (CARS). The nuclear envelope is linked to several lipodystrophies through mutations in lamin A; however, lamin A is widely expressed. Thus it is possible that the TMEM120A and B fat-specific nuclear envelope transmembrane proteins may play a contributory role in the tissue-specific pathology of this disorder or in the wider problem of obesity.</p></div

Observation of the diphoton decay of the Higgs boson and measurement of its properties

Peer reviewe

Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

Peer reviewe

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

Measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))in pp collisions at √s=8TeV

A measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))σ(χb2(1P))/σ(χb1(1P)) is presented. The χb1(1P)χb1(1P) and χb2(1P)χb2(1P) bottomonium states, promptly produced in pp collisions at View the MathML sources=8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays χb1,2(1P)→ϒ(1S)+γχb1,2(1P)→ϒ(1S)+γ. The emitted photons are measured through their conversion to e+e−e+e− pairs, whose reconstruction allows the two states to be resolved. The ϒ(1S)ϒ(1S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb−120.7 fb−1 is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |ηγ|<1.0|ηγ|<1.0; the ϒ(1S)ϒ(1S) rapidity, |yϒ|<1.5|yϒ|<1.5; and the ϒ(1S)ϒ(1S) transverse momentum, View the MathML source7<pTϒ<40 GeV. The cross section ratio shows no significant dependence on the ϒ(1S)ϒ(1S) transverse momentum, with a measured average value of View the MathML source0.85±0.07(stat+syst)±0.08(BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χbχb branching fractions