Simulating spin-3/2 particles at colliders

Support for interactions of spin-3/2 particles is implemented in the FeynRules and ALOHA packages and tested with the MadGraph 5 and CalcHEP event generators in the context of three phenomenological applications. In the first, we implement a spin-3/2 Majorana gravitino field, as in local supersymmetric models, and study gravitino and gluino pair-production. In the second, a spin-3/2 Dirac top-quark excitation, inspired from compositness models, is implemented. We then investigate both top-quark excitation and top-quark pair-production. In the third, a general effective operator for a spin-3/2 Dirac quark excitation is implemented, followed by a calculation of the angular distribution of the s-channel production mechanism.Comment: 20 pages, 7 figure

Improvement of psychiatrists’ clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ project: A nationwide dissemination, education, and evaluation study

© 2019 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

Weak itinerant ferromagnetism in Heusler type Fe2VAl0.95

We report measurements of the magnetic, transport and thermal properties of the Heusler type compound Fe2VAl0.95. We show that while stoichiometric Fe2VAl is a non-magnetic semi-metal a 5% substitution on the Al-site with the 3d elements Fe and V atoms leads to a ferromagnetic ground state with a Curie temperature TC = 33+-3 K and a small ordered moment ms = 0.12 mB/Fe in Fe2VAl0.95. The reduced value of the ratio ms/mp = 0.08, where mp = 1.4 mB/Fe is the effective Curie-Weiss moment, together with the analysis of the magnetization data M(H,T), show magnetism is of itinerant nature. The specific heat shows an unusual temperature variation at low temperatures with an enhanced Sommerfeld coefficient, g = 12 mJK-2mol-1. The resistivity, r(T), is metallic and follows a power law behavior r(T) = r0+AT^n with n = 1.5 below TC. With applying pressure, TC decreases with the rate of (1/TC)(dTC /dP) = -0.061 GPa-1. We conclude substitution on the Al-site with Fe and V atoms results in itinerant ferromagnetism with a low carrier density.Comment: 27 pages, 9 figure

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Collider signatures of goldstini in gauge mediation

We investigate the collider signatures of the multiple goldstini scenario in the framework of gauge mediation. This class of models is characterized by a visible sector (e.g. the MSSM or any extension) coupled by gauge interactions to more than one SUSY breaking sector. The spectrum consists of a light gravitino LSP, behaving as a goldstino, and a number of neutral fermions (the pseudo-goldstini) with a mass between that of the LSP and that of the lightest particle of the observable sector (LOSP). We consider the two situations where the LOSP is either a gaugino-like neutralino or a stau and we assume only one pseudo-goldstino of a mass of O(100) GeV. The coupling of the LOSP to the pseudo-goldstino can be enhanced with respect to those of the gravitino giving rise to characteristic signatures. We show that the decay modes of the LOSP into a SM particle and a pseudo-goldstino can be significant. For both LOSP scenarios we analyze (pseudo)-goldstini production at colliders. Compared to standard gauge mediation the final state spectrum is softer and more structured.Comment: v2: analysis of the stau LOSP scenario added, sections rearranged, and Introduction and Conclusions rewritten to include the added scenario. Version to appear in JHE

The Sno Oncogene Antagonizes Wingless Signaling during Wing Development in Drosophila

The Sno oncogene (Snoo or dSno in Drosophila) is a highly conserved protein and a well-established antagonist of Transforming Growth Factor-β signaling in overexpression assays. However, analyses of Sno mutants in flies and mice have proven enigmatic in revealing developmental roles for Sno proteins. Thus, to identify developmental roles for dSno we first reconciled conflicting data on the lethality of dSno mutations. Then we conducted analyses of wing development in dSno loss of function genotypes. These studies revealed ectopic margin bristles and ectopic campaniform sensilla in the anterior compartment of the wing blade suggesting that dSno functions to antagonize Wingless (Wg) signaling. A subsequent series of gain of function analyses yielded the opposite phenotype (loss of bristles and sensilla) and further suggested that dSno antagonizes Wg signal transduction in target cells. To date Sno family proteins have not been reported to influence the Wg pathway during development in any species. Overall our data suggest that dSno functions as a tissue-specific component of the Wg signaling pathway with modest antagonistic activity under normal conditions but capable of blocking significant levels of extraneous Wg, a role that may be conserved in vertebrates

Towards a Metric for the Assessment of Safety Critical Control Systems

There is a need for better integration of the fault tolerant and the control designs for safety critical systems such as aircraft. The dependability of current designs is assessed primarily with measures of the interconnection of fault tolerant components: the reliability function and the mean time to failure. These measures do not directly take into account the interaction of the fault tolerant components with the dynamics of the aircraft. In this paper, a first step to better integrate these designs is made. It is based on the observation that unstable systems are intrinsically unreliable and that a necessary condition for reliability is the existence of a stabilizing control law that depends on the interconnection of the working fault tolerant components. Since operation of a fault tolerant interconnection of digital computers in a harsh environment can result in transient errors, a methodology to analyze the mean square stability of the fault tolerant closed-loop system is presented. A definition for mean square stabilizability is then used to introduce the new dynamical system reliability concept. An example illustrates the effect on mean square stability of several fault tolerant design choices and illustrates possible dynamical system reliability plot

Phosphorylation of p65(RelA) on Ser547 by ATM Represses NF-κB-Dependent Transcription of Specific Genes after Genotoxic Stress

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65

<em>Enterococcus faecalis</em> Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-kappa B inflammatory response as well as impaired DNA damage response and cell cycle control gene expression

Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle

<p>Abstract</p> <p>Background</p> <p>Despite the widespread induction of miR-146a during the innate immune response little is known regarding its biogenesis, function and mechanism. We have therefore examined the role of miR-146a during the interleukin (IL)-1β-stimulated IL-6 and IL-8 release and proliferation in primary human airway smooth muscle (HASM) cells.</p> <p>Methods</p> <p>HASM cells were isolated from human lung re-section, cultured to a maximum of 3 - 6 passages and then exposed to IL-1β. miR-146a expression were determined by qRT-PCR, IL-6 and IL-8 release by ELISA and proliferation using bromodeoxyuridine incorporation. The role of NF-κB and the MAP kinase pathways was assessed using pharmacological inhibitors of IKK2 (TPCA-1), JNK (SP600125), p38 MAP kinase (SB203580) and MEK-1/2 (PD98059). miR-146a function was determined following transfection of HASM with inhibitors and mimics using Amaxa electroporation.</p> <p>Results</p> <p>IL-1β induced a time-dependent and prolonged 100-fold induction in miR-146a expression, which correlated with release of IL-6 and IL-8. Exposure to IL-1β had no effect upon HASM proliferation. Pharmacological studies showed that expression of primary miR-146a was regulated at the transcriptional levels by NF-κB whilst post-transcriptional processing to mature miR-146a was regulated by MEK-1/2 and JNK-1/2. Functional studies indicated that IL-1β-induced miR-146a expression does not negatively regulate IL-6 and IL-8 release or basal proliferation. However, inhibition of IL-1β-induced IL-6 and IL-8 release was observed at the super-maximal intracellular miR-146a levels obtained by transfection with miR-146a mimics and indicates that studies using miRNA mimics can produce false positive results. Mechanistic studies showed that in the presence of super-maximal levels, the action of miR-146a mimics was mediated at a step following IL-6 and IL-8 mRNA transcription and not through down-regulation of IL-1 receptor associated kinase 1 (IRAK-1) and TNF receptor-associated factor 6 (TRAF6) protein expression, two predicted miR-146a targets involved in IL-1β signalling.</p> <p>Conclusions</p> <p>We have shown that IL-1β-induced miR-146a expression in HASM and that this was regulated at the transcriptional level by NF-κB and at the post-transcriptional level by the MEK-1/2 and JNK-1/2. Unlike previous reports, studies using miRNA inhibitors showed that miR-146a expression did not regulate IL-6 and IL-8 release or proliferation and suggest miR-146a function and mechanism is cell-type dependent.</p