Gauge procedure with gauge fields of various ranks

The standard procedure for making a global phase symmetry local involves the introduction of a rank 1, vector field in the definition of the covariant derivative. Here it is shown that it is possible to gauge a phase symmetry using fields of various ranks. In contrast to other formulations of higher rank gauge fields we begin with the coupling of the gauge field to some matter field, and then derive the gauge invariant, field strength tensor. Some of these gauge theories are similar to general relativity in that their covariant derivatives involve derivatives of the rank n gauge field rather than just the gauge field. For general relativity the covariant derivative involves the Christoffel symbols which are written in terms of derivatives of the metric tensor. Many (but not all) of the Lagrangians that we find for these higher rank gauge theories lead to nonrenormalizable quantum theories which is also similar to general relativity.Comment: References adde

Therapeutic Intervention for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): A Systematic Review and Meta-Analysis

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been treated with several different interventions with limited success. This meta-analysis aims to review all trials reporting on therapeutic intervention for CP/CPPS using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Methods We searched Medline, PubMed, the Cochrane Pain, Palliative & Supportive Care Trials, the Cochrane Register of Controlled Trials, CINAHL, ClinicalTrials.gov, and the NIDDK website between 1947 and December 31, 2011 without language or study type restrictions. All RCTs for CP/CPPS lasting at least 6 weeks, with a minimum of 10 participants per arm, and using the NIH-CPSI score, the criterion standard for CP/CPPS, as an outcome measure were included. Data was extracted from each study by two independent reviewers. Gillbraith and I-squared plots were used for heterogeneity testing and Eggers and Peters methods for publication bias. Quality was assessed using a component approach and meta-regression was used to analyze sources of heterogeneity. Results: Mepartricin, percutaneous tibial nerve stimulation (PTNS), and triple therapy comprised of doxazosin + ibuprofen + thiocolchicoside (DIT) resulted in clinically and statistically significant reduction in NIH-CPSI total score. The same agents and aerobic exercise resulted in clinically and statistically significant NIH-CPSI pain domain score reduction. Acupuncture, DIT, and PTNS were found to produce statistically and clinically significant reductions in the NIH-CPSI voiding domain. A statistically significant placebo effect was found for all outcomes and time analysis showed that efficacy of all treatments increased over time. Alpha-blockers, antibiotics, and combinations of the two failed to show statistically or clinically significant NIH-CPSI reductions. Conclusion: Results from this meta-analysis reflect our current inability to effectively manage CP/CPPS. Clinicians and researchers must consider placebo effect and treatment efficacy over time and design studies creatively so we can more fully elucidate the etiology and role of therapeutic intervention in CP/CPPS.

Re-Os isotope and platinum group elements of a FOcal ZOne mantle source, Louisville Seamounts Chain, Pacific ocean

The Louisville Seamount Chain (LSC) is, besides the Hawaiian-Emperor Chain, one of the longest-lived hotspot traces. We report here the first Re-Os isotope and platinum group element (PGE) data for Canopus, Rigil, and Burton Guyots along the chain, which were drilled during IODP Expedition 330. The LSC basalts possess (187Os/188Os)i = 0.1245–0.1314 that are remarkably homogeneous and do not vary with age. A Re-Os isochron age of 64.9 ± 3.2 Ma was obtained for Burton seamount (the youngest of the three seamounts drilled), consistent with 40Ar-39Ar data. Isochron-derived initial 187Os/188Os ratio of 0.1272 ± 0.0008, together with data for olivines (0.1271–0.1275), are within the estimated primitive mantle values. This (187Os/188Os)i range is similar to those of Rarotonga (0.124–0.139) and Samoan shield (0.1276–0.1313) basalts and lower than those of Cook-Austral (0.136–0.155) and Hawaiian shield (0.1283–0.1578) basalts, suggesting little or no recycled component in the LSC mantle source. The PGE data of LSC basalts are distinct from those of oceanic lower crust. Variation in PGE patterns can be largely explained by different low degrees of melting under sulfide-saturated conditions of the same relatively fertile mantle source, consistent with their primitive mantle-like Os and primordial Ne isotope signatures. The PGE patterns and the low 187Os/188Os composition of LSC basalts contrast with those of Ontong Java Plateau (OJP) tholeiites. We conclude that the Re-Os isotope and PGE composition of LSC basalts reflect a relatively pure deep-sourced common mantle sampled by some ocean island basalts but is not discernible in the composition of OJP tholeiites

Supersymmetry, Spectrum and Fate of D0-Dp Systems with B-field

It has been shown that D0-D$p$ $(p=2, 4, 6, 8)$ systems can be BPS in the presence of $B$-field even if they are not otherwise. We review the number of remaining supersymmetries, the open string ground state spectrum and the construction of the D0-D$p$ systems as solitonic solutions in the noncommutative super Yang-Mills theory. We derive the complete mass spectrum of the fluctuations to discuss the stability of the systems. The results are found to agree with the analysis in the string picture. In particular, we show that supersymmetry is enhanced in D0-D8 depending on the $B$-fields and it is consistent with the degeneracy of mass spectrum. We also derive potentials and discuss their implications for these systems.Comment: 25 pages, minor correction

Inhibitors of MyD88-Dependent Proinflammatory Cytokine Production Identified Utilizing a Novel RNA Interference Screening Approach

The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA) library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR) dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A) under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS) resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA) library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses

Helicobacter pylori CagA Triggers Expression of the Bactericidal Lectin REG3γ via Gastric STAT3 Activation

Background: Most of what is known about the Helicobacter pylori (H. pylori) cytotoxin, CagA, pertains to a much-vaunted role as a determinant of gastric inflammation and cancer. Little attention has been devoted to potential roles of CagA in the majority of H. pylori infected individuals not showing oncogenic progression, particularly in relation to host tolerance. Regenerating islet-derived (REG)3c encodes a secreted C-type lectin that exerts direct bactericidal activity against Grampositive bacteria in the intestine. Here, we extend this paradigm of lectin-mediated innate immunity, showing that REG3c expression is triggered by CagA in the H. pylori-infected stomach. Methodology/Principal Findings: In human gastric mucosal tissues, REG3c expression was significantly increased in CagApositive, compared to CagA-negative H. pylori infected individuals. Using transfected CagA-inducible gastric MKN28 cells, we recapitulated REG3c induction in vitro, also showing that tyrosine phosphorylated, not unphosphorylated CagA triggers REG3c transcription. In concert with induced REG3c, pro-inflammatory signalling downstream of the gp130 cytokine coreceptor via the signal transducer and activator of transcription (STAT)3 and transcription of two cognate ligands, interleukin(IL)-11 and IL-6, were significantly increased. Exogenous IL-11, but not IL-6, directly stimulated STAT3 activation and REG3c transcription. STAT3 siRNA knockdown or IL-11 receptor blockade respectively abrogated or subdued CagAdependent REG3c mRNA induction, thus demonstrating a requirement for uncompromised signalling via the IL-11/STAT

Searching For Dark Matter with Plasma Haloscopes

We summarise the recent progress of the Axion Longitudinal Plasma HAloscope (ALPHA) Consortium, a new experimental collaboration to build a plasma haloscope to search for axions and dark photons. The plasma haloscope is a novel method for the detection of the resonant conversion of light dark matter to photons. ALPHA will be sensitive to QCD axions over almost a decade of parameter space, potentially discovering dark matter and resolving the Strong CP problem. Unlike traditional cavity haloscopes, which are generally limited in volume by the Compton wavelength of the dark matter, plasma haloscopes use a wire metamaterial to create a tuneable artificial plasma frequency, decoupling the wavelength of light from the Compton wavelength and allowing for much stronger signals. We develop the theoretical foundations of plasma haloscopes and discuss recent experimental progress. Finally, we outline a baseline design for ALPHA and show that a full-scale experiment could discover QCD axions over almost a decade of parameter space.Comment: Endorsers: Jens Dilling, Michael Febbraro, Stefan Knirck, and Claire Marvinney. 26 pages, 17 figures, version accepted in Physical Review

SOCS2 Influences LPS Induced Human Monocyte-Derived Dendritic Cell Maturation

Dendritic cells (DCs) are highly specific antigen presenting cells, which link innate and adaptive immune responses and participate in protecting hosts from invading pathogens. DCs can be generated in vitro by culturing human monocytes with GM-CSF and IL-4 followed by LPS induced DC maturation. We set out to study the suppressor of cytokine signaling (SOCS) proteins during maturation and activation of human monocyte-derived DCs from peripheral blood in vitro. We found that the expression of SOCS2 mRNA and protein is dramatically up-regulated during DC maturation. Silencing of SOCS2 using siRNA, inhibited DC maturation as evidenced by a decreased expression of maturation markers such as CD83, co-stimulatory molecules CD40, CD86 and HLA-DR. Furthermore, silencing of SOCS2 decreased LPS induced activation of MAP kinases (SAKP/JNK, p38, ERK), IRF3, decreased the translocation of the NF-κB transcription factor and reduced downstream gene mRNA expression. These results suggest a role for SOCS2 in the MyD88-dependent and -independent TLR4 signaling pathways. In conclusion, our results demonstrate that SOCS2 is required for appropriate TLR4 signaling in maturating human DCs via both the MyD88-dependent and -independent signaling pathway