P-odd and CP-odd Four-Quark Contributions to Neutron EDM

In a class of beyond-standard-model theories, CP-odd observables, such as the neutron electric dipole moment, receive significant contributions from flavor-neutral P-odd and CP-odd four-quark operators. However, considerable uncertainties exist in the hadronic matrix elements of these operators strongly affecting the experimental constraints on CP-violating parameters in the theories. Here we study their hadronic matrix elements in combined chiral perturbation theory and nucleon models. We first classify the operators in chiral representations and present the leading-order QCD evolutions. We then match the four-quark operators to the corresponding ones in chiral hadronic theory, finding symmetry relations among the matrix elements. Although this makes lattice QCD calculations feasible, we choose to estimate the non-perturbative matching coefficients in simple quark models. We finally compare the results for the neutron electric dipole moment and P-odd and CP-odd pion-nucleon couplings with the previous studies using naive factorization and QCD sum rules. Our study shall provide valuable insights on the present hadronic physics uncertainties in these observables.Comment: 40 pages, 7 figures. This is the final version. A discussion of the uncertainty of the calculation is adde

Filarial Lymphedema Is Characterized by Antigen- Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Methods and Findings: To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-c and TNF-a—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFb, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls. Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema

Flavor Physics in an SO(10) Grand Unified Model

In supersymmetric grand-unified models, the lepton mixing matrix can possibly affect flavor-changing transitions in the quark sector. We present a detailed analysis of a model proposed by Chang, Masiero and Murayama, in which the near-maximal atmospheric neutrino mixing angle governs large new b -> s transitions. Relating the supersymmetric low-energy parameters to seven new parameters of this SO(10) GUT model, we perform a correlated study of several flavor-changing neutral current (FCNC) processes. We find the current bound on B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on the lightest Higgs boson mass implies an important lower bound on tan beta, which in turn limits the size of the new FCNC transitions. Remarkably, the combined analysis does not rule out large effects in B_s-B_s-bar mixing and we can easily accomodate the large CP phase in the B_s-B_s-bar system which has recently been inferred from a global analysis of CDF and DO data. The model predicts a particle spectrum which is different from the popular Constrained Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces heavy masses, typically above 1 TeV, for the sfermions of the degenerate first two generations. However, the ratio of the third-generation and first-generation sfermion masses is smaller than in the CMSSM and a (dominantly right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes, Fig. 2 corrected; journal versio

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm

Over the past five decades, k-means has become the clustering algorithm of choice in many application domains primarily due to its simplicity, time/space efficiency, and invariance to the ordering of the data points. Unfortunately, the algorithm's sensitivity to the initial selection of the cluster centers remains to be its most serious drawback. Numerous initialization methods have been proposed to address this drawback. Many of these methods, however, have time complexity superlinear in the number of data points, which makes them impractical for large data sets. On the other hand, linear methods are often random and/or sensitive to the ordering of the data points. These methods are generally unreliable in that the quality of their results is unpredictable. Therefore, it is common practice to perform multiple runs of such methods and take the output of the run that produces the best results. Such a practice, however, greatly increases the computational requirements of the otherwise highly efficient k-means algorithm. In this chapter, we investigate the empirical performance of six linear, deterministic (non-random), and order-invariant k-means initialization methods on a large and diverse collection of data sets from the UCI Machine Learning Repository. The results demonstrate that two relatively unknown hierarchical initialization methods due to Su and Dy outperform the remaining four methods with respect to two objective effectiveness criteria. In addition, a recent method due to Erisoglu et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms (Springer, 2014). arXiv admin note: substantial text overlap with arXiv:1304.7465, arXiv:1209.196

Supersymmetric contributions to Bˉs→ϕπ0\bar{B}_s \to \phi \pi^0 and Bˉs→ϕρ0\bar{B}_s \to \phi \rho^0 decays in SCET

We study the decay modes $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$ using Soft Collinear Effective Theory. Within Standard Model and including the error due to the SU(3) breaking effect in the SCET parameters we find that BR $\bar{B}_s\to \phi \pi^0 =7_{-1-2}^{+1+2}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \pi^0=9_{-1-4}^{+1+3}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively.For the decay mode $\bar{B}_s\to \phi \rho^0$, we find that BR $\bar{B}_s\to \phi \rho^0 = 20.2^{+1+9}_{-1-12}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \rho^0 = 34.0^{+1.5 + 15}_{-1.5-22}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively. We extend our study to include supersymmetric models with non-universal A-terms where the dominant contributions arise from diagrams mediated by gluino and chargino exchanges. We show that gluino contributions can not lead to an enhancement of the branching ratios of $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$. In addition, we show that SUSY contributions mediated by chargino exchange can enhance the branching ratio of $\bar{B}_s\to \phi \pi^0$ by about 14% with respect to the SM prediction. For the branching ratio of $\bar{B}_s\to \phi \rho^0$, we find that SUSY contributions can enhance its value by about 1% with respect to the SM prediction.Comment: 25 pages,5 figures, version accepted for publicatio

Phenomenology of Light Sneutrino Dark Matter in cMSSM/mSUGRA with Inverse Seesaw

We study the possibility of a light Dark Matter (DM) within a constrained Minimal Supersymmetric Standard Model (cMSSM) framework augmented by a SM singlet-pair sector to account for the non-zero neutrino masses by inverse seesaw mechanism. Working within a 'hybrid' scenario with the MSSM sector fixed at high scale and the singlet neutrino sector at low scale, we find that, contrary to the case of the usual cMSSM where the neutralino DM cannot be very light, we can have a light sneutrino DM with mass below 100 GeV satisfying all the current experimental constraints from cosmology, collider as well as low-energy experiments. We also note that the supersymmetric inverse seesaw mechanism with sneutrino as the lightest supersymmetric partner can have enhanced same-sign dilepton final states with large missing transverse energy (mET) coming from the gluino- and squark-pair as well as the squark-gluino associated productions and their cascade decay through charginos. We present a collider study for the same-sign dilepton+jets+mET signal in this scenario and propose some distinctions with the usual cMSSM. We also comment on the implications of such a light DM scenario on the invisible decay width of an 125 GeV Higgs boson.Comment: 24 pages, 4 figures, 7 tables; matches published versio

Indeterminacy of Reverse Engineering of Gene Regulatory Networks: The Curse of Gene Elasticity

Gene Regulatory Networks (GRNs) have become a major focus of interest in recent years. A number of reverse engineering approaches have been developed to help uncover the regulatory networks giving rise to the observed gene expression profiles. However, this is an overspecified problem due to the fact that more than one genotype (network wiring) can give rise to the same phenotype. We refer to this phenomenon as “gene elasticity.” In this work, we study the effect of this particular problem on the pure, data-driven inference of gene regulatory networks.We simulated a four-gene network in order to produce “data” (protein levels) that we use in lieu of real experimental data. We then optimized the network connections between the four genes with a view to obtain the original network that gave rise to the data. We did this for two different cases: one in which only the network connections were optimized and the other in which both the network connections as well as the kinetic parameters (given as reaction probabilities in our case) were estimated. We observed that multiple genotypes gave rise to very similar protein levels. Statistical experimentation indicates that it is impossible to differentiate between the different networks on the basis of both equilibrium as well as dynamic data.We show explicitly that reverse engineering of GRNs from pure expression data is an indeterminate problem. Our results suggest the unsuitability of an inferential, purely data-driven approach for the reverse engineering transcriptional networks in the case of gene regulatory networks displaying a certain level of complexity

MeV-scale sterile neutrino decays at the Fermilab Short-Baseline Neutrino program

Nearly-sterile neutrinos with masses in the MeV range and below would be produced in the beam of the Short-Baseline Neutrino (SBN) program at Fermilab. In this article, we study the potential for SBN to discover these particles through their subsequent decays in its detectors. We discuss the decays which will be visible at SBN in a minimal and non-minimal extension of the Standard Model, and perform simulations to compute the parameter space constraints which could be placed in the absence of a signal. We demonstrate that the SBN programme can extend existing bounds on well constrained channels such as N → νl+l− and N → l±π∓ while, thanks to the strong particle identification capabilities of liquid-Argon technology, also place bounds on often neglected channels such as N → νγ and N → νπ0. Furthermore, we consider the phenomenological impact of improved event timing information at the three detectors. As well as considering its role in background reduction, we note that if the light-detection systems in SBND and ICARUS can achieve nanosecond timing resolution, the effect of finite sterile neutrino mass could be directly observable, providing a smoking-gun signature for this class of models. We stress throughout that the search for heavy nearly-sterile neutrinos is a complementary new physics analysis to the search for eV-scale oscillations, and would extend the BSM programme of SBN while requiring no beam or detector modifications