The Baryon-Dark Matter Ratio Via Moduli Decay After Affleck-Dine Baryogenesis

Low-scale supersymmetry breaking in string motivated theories implies the presence of O(100) TeV scale moduli, which generically lead to a significant modification of the history of the universe prior to Big Bang Nucleosynthesis. Such an approach implies a non-thermal origin for dark matter resulting from scalar decay, where the lightest supersymmetric particle can account for the observed dark matter relic density. We study the further effect of the decay on the baryon asymmetry of the universe, and find that this can satisfactorily address the problem of the over-production of the baryon asymmetry by the Affleck-Dine mechanism in the MSSM. Remarkably, there is a natural connection between the baryon and dark matter abundances today, which leads to a solution of the `Cosmic Coincidence Problem'.Comment: 12 pages, no figure. v2: references adde

Ultraviolet Emission Lines in Young Low Mass Galaxies at z~2: Physical Properties and Implications for Studies at z>7

We present deep spectroscopy of 17 very low mass (M* ~ 2.0x10^6 Msun to 1.4x10^9 Msun) and low luminosity (M_UV ~ -13.7 to -19.9) gravitationally lensed galaxies in the redshift range z~1.5-3.0. Deep rest-frame ultraviolet spectra reveal large equivalent width emission from numerous lines (NIV], OIII], CIV, Si III], CIII]) which are rarely seen in individual spectra of more massive star forming galaxies. CIII] is detected in 16 of 17 low mass star forming systems with rest-frame equivalent widths as large as 13.5 Angstroms. Nebular CIV emission is present in the most extreme CIII] emitters, requiring an ionizing source capable of producing a substantial component of photons with energies in excess of 47.9 eV. Photoionization models support a picture whereby the large equivalent widths are driven by the increased electron temperature and enhanced ionizing output arising from metal poor gas and stars, young stellar populations, and large ionization parameters. The young ages implied by the emission lines and continuum SEDs indicate that the extreme line emitters in our sample are in the midst of a significant upturn in their star formation activity. The low stellar masses, blue UV colors, and large sSFRs of our sample are similar to those of typical z>6 galaxies. Given the strong attenuation of Ly-alpha in z>6 galaxies we suggest that CIII] is likely to provide our best probe of early star forming galaxies with ground-based spectrographs and one of the most efficient means of confirming z>10 galaxies with the James Webb Space Telescope.Comment: 22 pages, 8 figures, accepted for publication in MNRA

Painlev\'e V and a Pollaczek-Jacobi type orthogonal polynomials

We study a sequence of polynomials orthogonal with respect to a one parameter family of weights w(x):=w(x,t)=\rex^{-t/x}\:x^{\al}(1-x)^{\bt},\quad t\geq 0, defined for $x\in[0,1].$ If $t=0,$ this reduces to a shifted Jacobi weight. Our ladder operator formalism and the associated compatibility conditions give an easy determination of the recurrence coefficients. For $t>0,$ the factor \rex^{-t/x} induces an infinitely strong zero at $x=0.$ With the aid of the compatibility conditions, the recurrence coefficients are expressed in terms of a set of auxiliary quantities that satisfy a system of difference equations. These, when suitably combined with a pair of Toda-like equations derived from the orthogonality principle, show that the auxiliary quantities are a particular Painlev\'e V and/or allied functions. It is also shown that the logarithmic derivative of the Hankel determinant, D_n(t):=\det(\int_{0}^{1} x^{i+j} \:\rex^{-t/x}\:x^{\al}(1-x)^{\bt}dx)_{i,j=0}^{n-1}, satisfies the Jimbo-Miwa-Okamoto $\sigma-$form of the Painlev\'e V and that the same quantity satisfies a second order non-linear difference equation which we believe to be new.Comment: 23 pages, typos corrected, references adde

Mechanistic Assessment of Extrahepatic Contributions to Glucuronidation of Integrase Strand Transfer Inhibitors

Integrase strand transfer inhibitor (INSTI)-based regimens dominate initial human immunodeficiency virus treatment. Most INSTIs are metabolized predominantly via UDP-glucuronosyltransferases (UGTs). For drugs predominantly metabolized by UGTs, including INSTIs, in vitro data recovered from human liver microsomes (HLMs) alone often underpredict human oral clearance. While several factors may contribute, extrahepatic glucuronidation may contribute to this underprediction. Thus, we comprehensively characterized the kinetics for the glucuronidation of INSTIs (cabotegravir, dolutegravir, and raltegravir) using pooled human microsomal preparations from liver (HLMs), intestine (HIMs), and kidney (HKMs) tissues; human embryonic kidney 293 cells expressing individual UGTs; and recombinant UGTs. In vitro glucuronidation of cabotegravir (HLMs≈HKMs>>>HIMs), dolutegravir (HLMs>HIMs>>HKMs), and raltegravir (HLMs>HKMs>> HIMs) occurred in hepatic and extrahepatic tissues. The kinetic data from expression systems suggested the major enzymes in each tissue: hepatic UGT1A9 > UGT1A1 (dolutegravir and raltegravir) and UGT1A1 (cabotegravir), intestinal UGT1A3 > UGT1A8 > UGT1A1 (dolutegravir) and UGT1A8 > UGT1A1 (raltegravir), and renal UGT1A9 (dolutegravir and raltegravir). Enzymes catalyzing cabotegravir glucuronidation in the kidney and intestine could not be identified unequivocally. Using data from dolutegravir glucuronidation as a prototype, a "bottom-up" physiologically based pharmacokinetic model was developed in a stepwise approach and predicted dolutegravir oral clearance within 4.5-fold (hepatic data only), 2-fold (hepatic and intestinal data), and 32% (hepatic, intestinal, and renal data). These results suggest clinically meaningful glucuronidation of dolutegravir in tissues other than the liver. Incorporation of additional novel mechanistic and physiologic underpinnings of dolutegravir metabolism along with in silico approaches appears to be a powerful tool to accurately predict the clearance of dolutegravir from in vitro data

The Baryon-Dark Matter Ratio Via Moduli Decay After Affleck-Dine Baryogenesis

Low-scale supersymmetry breaking in string motivated theories implies the presence of O(100) TeV scale moduli, which generically lead to a significant modification of the history of the universe prior to Big Bang Nucleosynthesis. Such an approach implies a non-thermal origin for dark matter resulting from scalar decay, where the lightest supersymmetric particle can account for the observed dark matter relic density. We study the further effect of the decay on the baryon asymmetry of the universe, and find that this can satisfactorily address the problem of the over-production of the baryon asymmetry by the Affleck-Dine mechanism in the MSSM. Remarkably, there is a natural connection between the baryon and dark matter abundances today, which leads to a solution of the `Cosmic Coincidence Problem\u27

Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly

Objectives. To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages

miR-200a Prevents Renal Fibrogenesis Through Repression of TGF-β2 Expression

OBJECTIVE: Progressive fibrosis in the diabetic kidney is driven and sustained by a diverse range of profibrotic factors. This study examines the critical role of microRNAs (miRNAs) in the regulation of the key fibrotic mediators, TGF-β1 and TGF-β2. RESEARCH DESIGN AND METHODS: Rat proximal-tubular epithelial cells (NRK52E) were treated with TGF-β1 and TGF-β2 for 3 days, and expression of markers of epithelial-to-mesenchymal transition (EMT) and fibrogenesis were assessed by RT-PCR and Western blotting. The expression of miR-141 and miR-200a was also assessed, as was their role as translational repressors of TGF-β signaling. Finally, these pathways were explored in two different mouse models, representing early and advanced diabetic nephropathy. RESULTS: Both TGF-β1 and TGF-β2 induced EMT and fibrogenesis in NRK52E cells. TGF-β1 and TGF-β2 also downregulated expression of miR-200a. The importance of these changes was demonstrated by the finding that ectopic expression miR-200a downregulated smad-3 activity and the expression of matrix proteins and prevented TGF-β-dependent EMT. miR-200a also downregulated the expression of TGF-β2, via direct interaction with the 3' untranslated region of TGF-β2. The renal expression of miR-141 and miR-200a was also reduced in mouse models representing early and advanced kidney disease. CONCLUSIONS: miR-200a and miR-141 significantly impact on the development and progression of TGF-β-dependent EMT and fibrosis in vitro and in vivo. These miRNAs appear to be intricately involved in fibrogenesis, both as downstream mediators of TGF-β signaling and as components of feedback regulation, and as such represent important new targets for the prevention of progressive kidney disease in the context of diabetes

Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)

The understanding of Earth’s biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E. maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E. maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E. maximus