SmO thin films: a flexible route to correlated flat bands with nontrivial topology

Using density functional theory based calculations, we show that the correlated mixed-valent compound SmO is a 3D strongly topological semi-metal as a result of a 4$f$-5$d$ band inversion at the X point. The [001] surface Bloch spectral density reveals two weakly interacting Dirac cones that are quasi-degenerate at the M_bar-point and another single Dirac cone at the Gamma_bar-point. We also show that the topological non-triviality in SmO is very robust and prevails for a wide range of lattice parameters, making it an ideal candidate to investigate topological nontrivial correlated flat bands in thin-film form. Moreover, the electron filling is tunable by strain. In addition, we find conditions for which the inversion is of the 4f-6s type, making SmO to be a rather unique system. The similarities of the crystal symmetry and the lattice constant of SmO to the well studied ferromagnetic semiconductor EuO, makes SmO/EuO thin film interfaces an excellent contender towards realizing the quantum anomalous Hall effect in a strongly correlated electron system.Comment: Paper+supplemen

Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP kinase kinase 6.

BackgroundConventional p38α inhibitors have limited efficacy in rheumatoid arthritis, possibly because p38 blockade suppresses the counter-regulatory mechanisms that limit inflammation. In contrast, targeting the upstream MAP kinase kinases, MKK3 and MKK6, partially maintains p38-mediated anti-inflammatory responses in bone marrow-derived macrophages (BMDM). In this study, we explored the mechanisms that preserve anti-inflammatory gene expression by evaluating differential regulation of IL-10 and p38-dependent anti-inflammatory genes in MKK3-/-, MKK6-/-, and p38 inhibitor-treated wildtype cells.MethodsBMDM from wild type (WT), MKK3-/-, and MKK6-/- mice were pre-treated with p38 inhibitor SB203580 (SB), JNK inhibitor SP600125 (SP), and/or ERK inhibitor PD98059 (PD) and stimulated with LPS. Supernatant protein levels were measured by multiplex bead immunoassay. mRNA expression was determined by qPCR and protein expression by Western blot analysis. De novo IL-10 mRNA synthesis was quantified in cells treated with ethynyl-uridine and LPS followed by reverse transcription and qPCR. mRNA half-life was measured in LPS-treated cells that were then incubated with actinomycin D ± SB203580.ResultsPre-treatment of WT BMDM with p38 inhibitor significantly reduced IL-10 production in the three groups, while ERK and JNK inhibitors had minimal effects. IL-10 production was significantly decreased in MKK3-/- BMDM compared with either WT or MKK6-/- cells. IL-10 mRNA expression was modestly reduced in MKK3-/- BMDM but was preserved in MKK6-/- cells compared with WT. De novo IL-10 mRNA synthesis was inhibited in MKK3-/- and p38 inhibitor pre-treated cells, but not MKK6-/- cells compared with WT. IL-10 mRNA half-life was markedly reduced in p38 inhibitor-treated WT cells while MKK-deficiency had minimal effect. DUSP1 mRNA levels were preserved in MKK-deficient cells but not in p38 inhibitor-treated WT cells. Tristetraprolin mRNA and protein levels were reduced in p38 inhibitor-treated WT cells compared with MKK6-/- cells.ConclusionUnlike p38-inhibition, the absence of MKK6 mostly preserves IL-10 and TTP protein expression in BMDM. MKK6-deficiency also spares DUSP1 and IL-1RA, which are key negative regulators of the inflammatory response. Together, these data suggest that MKK6 is a potential therapeutic target in RA

Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes.

c-Jun N-terminal kinase (JNK) contributes to metalloproteinase (MMP) gene expression and joint destruction in inflammatory arthritis. It is phosphorylated by at least two upstream kinases, the mitogen-activated protein kinase kinases (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs). However, the MEKKs that are most relevant to JNK activation in synoviocytes have not been determined. These studies were designed to assess the hierarchy of upstream MEKKs, MEKK1, MEKK2, MEKK3, and transforming growth factor-beta activated kinase (TAK)1, in rheumatoid arthritis (RA). Using either small interfering RNA (siRNA) knockdown or knockout fibroblast-like synoviocytes (FLSs), MEKK1, MEKK2, or MEKK3 deficiency (either alone or in combination) had no effect on IL-1beta-stimulated phospho-JNK (P-JNK) induction or MMP expression. However, TAK1 deficiency significantly decreased P-JNK, P-MKK4 and P-MKK7 induction compared with scrambled control. TAK1 knockdown did not affect p38 activation. Kinase assays showed that TAK1 siRNA significantly suppressed JNK kinase function. In addition, MKK4 and MKK7 kinase activity were significantly decreased in TAK1 deficient FLSs. Electrophoretic mobility shift assays demonstrated a significant decrease in IL-1beta induced AP-1 activation due to TAK1 knockdown. Quantitative PCR showed that TAK1 deficiency significantly decreased IL-1beta-induced MMP3 gene expression and IL-6 protein expression. These results show that TAK1 is a critical pathway for IL-1beta-induced activation of JNK and JNK-regulated gene expression in FLSs. In contrast to other cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA

RNA interference screening reveals host CaMK4 as a regulator of cryptococcal uptake and pathogenesis

ABSTRACT Cryptococcus neoformans , the causative agent of cryptococcosis, is an opportunistic fungal pathogen that kills over 200,000 individuals annually. This yeast may grow freely in body fluids, but it also flourishes within host cells. Despite extensive research on cryptococcal pathogenesis, host genes involved in the initial engulfment of fungi and subsequent stages of infection are woefully understudied. To address this issue, we combined short interfering RNA silencing and a high-throughput imaging assay to identify host regulators that specifically influence cryptococcal uptake. Of 868 phosphatase and kinase genes assayed, we discovered 79 whose silencing significantly affected cryptococcal engulfment. For 25 of these, the effects were fungus specific, as opposed to general alterations in phagocytosis. Four members of this group significantly and specifically altered cryptococcal uptake; one of them encoded CaMK4, a calcium/calmodulin-dependent protein kinase. Pharmacological inhibition of CaMK4 recapitulated the observed defects in phagocytosis. Furthermore, mice deficient in CaMK4 showed increased survival compared to wild-type mice upon infection with C. neoformans . This increase in survival correlated with decreased expression of pattern recognition receptors on host phagocytes known to recognize C. neoformans . Altogether, we have identified a kinase that is involved in C. neoformans internalization by host cells and in host resistance to this deadly infection. </jats:p

Coupled Bunch Instabilities in the LHC

In the LHC, the coupled bunch instabilities will be mainly driven by the RF cavities and the resistive wall effect. The growth times of these instabilities have been estimated taking into consideration the undamped and damped higher order modes of these cavities. These estimates show that the rise times of the longitudinal coupled bunch instabilities are under control. The proposed transverse feed-back system allows the same conclusion to be drawn for the transverse resistive wall instability

Study of menstrual disorder in adolescent girls at tertiary care centre in rural area

Background: Total adolescent world population is 16%.  Adolescents (10-19 years) constitute 21.3% i.e. nearly 1/5th of total population of India. 19% of the total population-faces a series of serious challenges not only affecting their growth and development but also their livelihood as adults. The objective of the current study was to observe the menstrual disorders among adolescent females and to observe the demographic profile and assess hygiene practices during menstruation and grade of anemia due to menstrual morbidity.  Methods: A random selection of adolescent’s females were done from gynaecology outpatient department at a tertiary care hospital in rural area. Study done on 180 adolescent girls from January 01, 2016 to June 31st, 2017, it is a descriptive type of observational study. Counseling done of adolescent females on menstrual hygiene and nutrition. Results: Most common menstrual morbidity seen in this study is dysmenorrhea (41.66%) followed by heavy menstrual bleeding i.e 25% and irregular menstrual bleeding (13.33%) subsequently. All these problems are associated with their practices used during menstruation. Poor menstrual hygiene was seen associated with 30 to 35% of abdominal cramps and mood swings, heavy menstrual bleeding and nutritional deficiency leads to moderate anemia (7 to10 gm%) in 83%.Conclusions: Due to unhygienic practices and lack of education and awareness about hygiene many of the girls were suffering from reproductive tract infections and poor nutrition leads to anemia. So, we all need to educate them about hygiene and spread awareness about the various services provided by the government like supplying of sanitary napkins to overcome infections

Regulation of peripheral inflammation by spinal p38 MAP kinase in rats.

BackgroundSomatic afferent input to the spinal cord from a peripheral inflammatory site can modulate the peripheral response. However, the intracellular signaling mechanisms in the spinal cord that regulate this linkage have not been defined. Previous studies suggest spinal cord p38 mitogen-activated protein (MAP) kinase and cytokines participate in nociceptive behavior. We therefore determined whether these pathways also regulate peripheral inflammation in rat adjuvant arthritis, which is a model of rheumatoid arthritis.Methods and findingsSelective blockade of spinal cord p38 MAP kinase by administering the p38 inhibitor SB203580 via intrathecal (IT) catheters in rats with adjuvant arthritis markedly suppressed paw swelling, inhibited synovial inflammation, and decreased radiographic evidence of joint destruction. The same dose of SB203580 delivered systemically had no effect, indicating that the effect was mediated by local concentrations in the neural compartment. Evaluation of articular gene expression by quantitative real-time PCR showed that spinal p38 inhibition markedly decreased synovial interleukin-1 and -6 and matrix metalloproteinase (MMP3) gene expression. Activation of p38 required tumor necrosis factor alpha (TNFalpha) in the nervous system because IT etanercept (a TNF inhibitor) given during adjuvant arthritis blocked spinal p38 phosphorylation and reduced clinical signs of adjuvant arthritis.ConclusionsThese data suggest that peripheral inflammation is sensed by the central nervous system (CNS), which subsequently activates stress-induced kinases in the spinal cord via a TNFalpha-dependent mechanism. Intracellular p38 MAP kinase signaling processes this information and profoundly modulates somatic inflammatory responses. Characterization of this mechanism could have clinical and basic research implications by supporting development of new treatments for arthritis and clarifying how the CNS regulates peripheral immune responses

Intermediate Review of Single Bunch Collective Effects in the LHC

This paper presents an intermediate review of the single bunch collective effects in the LHC. It first reviews the LHC impedance budget including all elements for which a design is presently available. Then, based on this updated budget, the corresponding rise times and thresholds for single bunch instabilities are evaluated and discussed

Correlation of wrist circumference with waist circumference and body mass index in adults with early-onset type 2 diabetes mellitus

Background: Recent studies have shown that wrist circumference is correlated with insulin resistance, obesity and new onset diabetes. Being easy to measure, it may be useful in identifying individuals at risk for cardio- metabolic disorders.Methods: 112 consecutive subjects with new onset type 2 diabetes in the age group 18-44 years were included in the study. Socio demographic characteristics, anthropometric and biochemical measurements were carried out using standard techniques. Pearson product movement Correlation Coefficient was used to find out correlation with other measures of obesity and ROC curve to determine its cut off values.Results: Wrist circumference showed moderate positive correlation with BMI (r+0.389) and waist circumference (r+0.443). The cut off value of wrist circumference when compared with BMI in defining obesity was 16.5cm in male and 15.7 cm in female. The cut off value of wrist circumference with waist circumference in male was 16.2cm.Conclusions: Measurement of wrist circumference may supplement in assessing obesity especially when other measures of obesity like BMI or Waist circumference measurements are difficult or not feasible

Nanotechnology and the Developing World

How nanotechnology can be harnessed to address some of the world's most critical development problem