BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish

Anomalous U(1), holomorphy, supersymmetry breaking and dilaton stabilization

We argue that in certain models with family symmetries the implementation of the alignment mechanism for the supression of the flavor changing neutral currents requires mass matrices with holomorphic zeros in the down quark sector. Holomorphic zeros typically open flat directions that potentially spoil the uniqueness of the supersymmetric vacuum. We then present an anomalous U(1) model without holomorphic zeros in the quark sector that can reproduce the fermion mass hierarchies, provided that $\tan{\beta}$ is of order one. To avoid undesired flavor changing neutral currents we propose a supersymmetry breaking mechanism and a dilaton stabilization scenario that result in degenerate squarks at $M\sim M_{GUT}$ and a calculable low energy spectrum. We present the numerical predictions of this model for the Higgs mass for different values of $M$ and $\tan{\beta}$.Comment: 14 pages, no figures; wording of the abstract is change

Psychological Health Influences of Legal-Marriage and -Partnerships on Same-Sex Couples

This chapter explores whether Californians in same-sex legal marriages and partnerships reported lower levels of psychological distress than other adult Californians after the 2008 California Supreme Court Decision that legalized same-sex marriage. We pooled 10 years of California Health Interview Survey (CHIS) data and employ a T1-T2 design to approximate a time series design. Dependent variables include overall self-related health, psychological distress, and household income. Independent variables include sexual identity and same-sex spouse. Bi-variate analyses compared self-reported mental and physical health between the two periods. We found decreased reports of poorer health and increased reports of very good health among gay men and lesbian women with legal spouses. Psychological distress decreased for legally coupled gay men and lesbians while increased slightly among unpartnered lesbian women and gay men. Household income increased among coupled lesbian women and gay men and decreased among others. Our project demonstrated positive health influences for Californians with legal same-sex spouses. We recommend future research projects that explore whether and how same- and opposite-sex marriage benefits health, well-being, and prosperity, and for marital status survey questions that are inclusive of sexual and gender identities and elicit the sex/gender of a respondent’s spouse

K^+ -> pi^+pi^0e^+e^-: a novel short-distance probe

We study the decay K^+ -> pi^+ pi^0 e^+ e^-, currently under analysis by the NA62 Collaboration at CERN. In particular, we provide a detailed analysis of the Dalitz plot for the long-distance, gamma^*-mediated, contributions (Bremsstrahlung, direct emission and its interference). We also examine a set of asymmetries to isolate genuine short-distance effects. While we show that charge asymmetries are not required to test short distances, they provide the best environment for its detection. This constitutes by itself a strong motivation for NA62 to study K^- decays in the future. We therefore provide a detailed study of different charge asymmetries and the corresponding estimated signals. Whenever possible, we make contact with the related processes K^+ -> pi^+ pi^0 gamma and K_L -> pi^+ pi^- e^+ e^- and discuss the advantages of K^+ -> pi^+ pi^0 e^+ e^- over them.Comment: 25 pages, 6 figure

Dynamical supersymmetry breaking in a superstring inspired model

We present a dilaton dominated scenario for supersymmetry breaking in a recently constructed realistic superstring inspired model with an anomalous U(1) symmetry. Supersymmetry is broken via gaugino condensation due to a confining SU(Nc) gauge group in the hidden sector. In particular, we find that by imposing on the model the phenomenological constraint of the absence of observed flavor changing neutral currents, there is a range of parameters related to the hidden sector and the Kahler potential for which we obtain a low energy spectrum consistent with present experimental bounds. As an illustrative example, we derive the low energy spectrum of a specific model. We find that the LSP is the lightest neutralino with a mass of 53 GeV and the lightest Higgs has a mass of 104 GeV.Comment: 13 page

Renormalisation Group Analysis of Single Right-handed Neutrino Dominance

We perform a renormalisation group (RG) analysis of neutrino masses and mixing angles in the see-saw mechanism in the minimal supersymmetric standard model with three right-handed neutrinos, including the effects of the heavy neutrino thresholds. We focus on the case that one of the right-handed neutrinos provides the dominant contribution to the 23 block of the light Majorana matrix, causing its determinant to approximately vanish and giving an automatic neutrino mass hierarchy, so called single right-handed neutrino dominance which may arise from a U(1) family symmetry. In these models radiative corrections can increase atomospheric and solar neutrino mixing by up to about 10% and 5%, respectively, and may help to achieve bi-maximal mixing. Significantly we find that the radiative corrections over the heavy neutrino threshold region are at least as important as those usually considered from the lightest right-handed neutrino down to low energies.Comment: Version to appear in Nuclear Physics B. 30 pages, Late

Dynamic Zebrafish Interactome Reveals Transcriptional Mechanisms of Dioxin Toxicity

In order to generate hypotheses regarding the mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) causes toxicity, we analyzed global gene expression changes in developing zebrafish embryos exposed to this potent toxicant in the context of a dynamic gene network. For this purpose, we also computationally inferred a zebrafish (Danio rerio) interactome based on orthologs and interaction data from other eukaryotes.Using novel computational tools to analyze this interactome, we distinguished between dioxin-dependent and dioxin-independent interactions between proteins, and tracked the temporal propagation of dioxin-dependent transcriptional changes from a few genes that were altered initially, to large groups of biologically coherent genes at later times. The most notable processes altered at later developmental stages were calcium and iron metabolism, embryonic morphogenesis including neuronal and retinal development, a variety of mitochondria-related functions, and generalized stress response (not including induction of antioxidant genes). Within the interactome, many of these responses were connected to cytochrome P4501A (cyp1a) as well as other genes that were dioxin-regulated one day after exposure. This suggests that cyp1a may play a key role initiating the toxic dysregulation of those processes, rather than serving simply as a passive marker of dioxin exposure, as suggested by earlier research.Thus, a powerful microarray experiment coupled with a flexible interactome and multi-pronged interactome tools (which are now made publicly available for microarray analysis and related work) suggest the hypothesis that dioxin, best known in fish as a potent cardioteratogen, has many other targets. Many of these types of toxicity have been observed in mammalian species and are potentially caused by alterations to cyp1a

AMI-LA Observations of the SuperCLASS Super-cluster

We present a deep survey of the SuperCLASS super-cluster - a region of sky known to contain five Abell clusters at redshift $z\sim0.2$ - performed using the Arcminute Microkelvin Imager (AMI) Large Array (LA) at 15.5$~$GHz. Our survey covers an area of approximately 0.9 square degrees. We achieve a nominal sensitivity of $32.0~\mu$Jy beam$^{-1}$ toward the field centre, finding 80 sources above a $5\sigma$ threshold. We derive the radio colour-colour distribution for sources common to three surveys that cover the field and identify three sources with strongly curved spectra - a high-frequency-peaked source and two GHz-peaked-spectrum sources. The differential source count (i) agrees well with previous deep radio source count, (ii) exhibits no evidence of an emerging population of star-forming galaxies, down to a limit of 0.24$~$mJy, and (iii) disagrees with some models of the 15$~$GHz source population. However, our source count is in agreement with recent work that provides an analytical correction to the source count from the SKADS Simulated Sky, supporting the suggestion that this discrepancy is caused by an abundance of flat-spectrum galaxy cores as-yet not included in source population models.Comment: 17 pages, 14 figures, 3 tables. Accepted for publication in MNRA

Neutrino Parameters, Abelian Flavor Symmetries, and Charged Lepton Flavor Violation

Neutrino masses and mixings have important implications for models of fermion masses, and, most directly, for the charged lepton sector. We consider supersymmetric Abelian flavor models, where neutrino mass parameters are related to those of charged leptons and sleptons. We show that processes such as \tau to \mu\gamma, \mu to e\gamma and \mu-e conversion provide interesting probes. In particular, some existing models are excluded by current bounds, while many others predict rates within reach of proposed near future experiments. We also construct models in which the predicted rates for charged lepton flavor violation are below even the proposed experimental sensitivities, but argue that such models necessarily involve loss of predictive power.Comment: 27 pages, refs added, published versio