A Faddeev-Niemi Solution that Does Not Satisfy Gauss' Law

Faddeev and Niemi have proposed a reformulation of SU(2) Yang-Mills theory in terms of a U(1) gauge theory with 8 off-shell degrees of freedom. We present a solution to Faddeev and Niemi's formulation which does not solve the SU(2) Yang-Mills Gauss constraints. This demonstrates that the proposed reformulation is inequivalent to Yang-Mills, but instead describes Yang-Mills coupled to a particular choice of external charge.Comment: 10 pages, no figure

Association analysis of polymorphism in KIAA1717, HUMMLC2B, DECR1 and FTO genes with meat quality traits of the Berkshire breed

Single nucleotide polymorphisms (SNPs) in KIAA1717, HUMMLC2B, DECR1, and FTO genes have been found to be associated with some pork meat quality traits. In this study, we discovered that, in addition to meat quality traits reported previously, SNPs in these genes also are significantly associated with other meat quality traits in the Berkshire breed. A total of 323 Berkshire pigs bred under the same conditions were used for meat quality evaluation and polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP) genotyping analyses. The association analysis of RFLP genotyping with meat quality traits revealed that the SNPs in these 4 genes have novel associations with multiple meat quality traits (p < 0.01 or p < 0.05); a SNP in KIAA1717 was associated with meat color (CIE L), backfat thickness, drip loss, water-holding capacity, and pH24hr; a SNP in HUMMLC2B was associated with chemical composition (collagen), drip loss, shear force, and pH24hr; a SNP in DECR1 was associated with meat color (CIE a and b) and backfat thickness; and a SNP in FTO was associated with meat color (CIE L, a and b), protein content, drip loss, and water-holding capacity. Taken collectively, our results suggest that these 4 SNPs may be used for marker-assisted selection as a genetic marker for meat quality traits in Berkshire pigs.Key words: Berkshire, genetic markers, meat quality, SN

Sphingosine 1-phosphate receptor 4 promotes nonalcoholic steatohepatitis by activating NLRP3 inflammasome

BACKGROUND & AIMS: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. METHODS: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n-octylphenyl)ethyl]-1,3-propanediol hydrochloride)-like sphingolipid-focused library. RESULTS: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4(++/-) mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domaincontainning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4(+/-) mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome. CONCLUSIONS: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Electronic Structure of YbB 6 : Is it a Topological Insulator or Not?

To finally resolve the controversial issue of whether or not the electronic structure of YbB6 is nontrivially topological, we have made a combined study using angle-resolved photoemission spectroscopy (ARPES) of the nonpolar (110) surface and density functional theory (DFT). The flat-band conditions of the (110) ARPES avoid the strong band bending effects of the polar (001) surface and definitively show that YbB6 has a topologically trivial B 2p-Yb 5d semiconductor band gap of similar to 0.3 eV. Accurate determination of the low energy band topology in DFT requires the use of a modified Becke-Johnson exchange potential incorporating spin-orbit coupling and an on-site Yb 4f Coulomb interaction U as large as 7 eV. The DFT result, confirmed by a more precise GW band calculation, is similar to that of a small gap non-Kondo nontopological semiconductor. Additionally, the pressure-dependent electronic structure of YbB6 is investigated theoretically and found to transform into a p-d overlap semimetal with small Yb mixed valency.open11119sciescopu

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer

A closer look at the increase in suicide rates in South Korea from 1986–2005

<p>Abstract</p> <p>Background</p> <p>Suicide rates have recently been decreasing on average among OECD countries, but increasing trends have been detected in South Korea, particularly since the 1997 economic crisis. There have been no detailed analyses about the changes of the suicide rates over time periods in Korea. We examined trends in both absolute and proportional suicide rates over the time period of economic development, crisis, and recovery (1986 – 2005) as well as in birth cohorts from 1924 to 1978.</p> <p>Methods</p> <p>We used data on total mortality and suicide rates from 1986 to 2005 published online by the Korean National Statistical Office (NSO) and extracted data for individuals under 80 years old. The analyses of the trends for 1) the sex-age-specific total mortality rate, 2) the sex-age-specific suicide rate, and 3) the sex-age-specific proportional suicide rate in 1986–2005 were conducted. To demonstrate the birth cohort effect on the proportional suicide rate, the synthetic birth cohort from 1924 to 1978 from the successive cross-sectional data was constructed.</p> <p>Results</p> <p>Age standardized suicide rates in South Korea increased by 98% in men (from 15.3 to 30.3 per 100,000) and by 124% in women (from 5.8 to 13.0 per 100,000). In both genders, the proportional increase in suicide rates was more prominent among the younger group aged under 45, despite the absolute increase being attributed to the older group. There were distinct cohort effects underlying increasing suicide rates particularly among younger age groups.</p> <p>Conclusion</p> <p>Increasing suicide rates in Korea was composed of a greater absolute increase in the older group and a greater proportional increase in the younger group.</p

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let