On the Clustering of GRBs on the Sky

The two-point correlation of the 4th (current) BATSE catalog (2494 objects) is calculated. It is shown to be consistent with zero at nearly all angular scales of interest. Assuming that GRBs trace the large scale structure in the universe we calculate the angular correlation function for the standard CDM (sCDM) model. It is shown to be $\le 10^{-4}$ at $\theta \simeq 5^\circ$ if the BATSE catalog is assumed to be a volume-limited sample up to $z \simeq 1$. Combined with the error analysis on the BATSE catalog this suggests that nearly $10^5$ GRBs will be needed to make a positive detection of the two-point angular correlation function at this angular scale.Comment: 5 pages, Latex with aipproc.sty, incl. 1 ps-Fig., Proc. of the 5th Huntsville Gamma Ray Burst Symposium, Oct. 1999, ed. R.M. Kippen, AI

Primordial magnetic field limits from cosmological data

We study limits on a primordial magnetic field arising from cosmological data, including that from big bang nucleosynthesis, cosmic microwave background polarization plane Faraday rotation limits, and large-scale structure formation. We show that the physically-relevant quantity is the value of the effective magnetic field, and limits on it are independent of how the magnetic field was generated.Comment: 7 pages, 6 figure

Contribution of Galaxies to the Background Hydrogen-Ionizing Flux

We estimate the evolution of the contribution of galaxies to the cosmic background flux at $912 \AA$ by means of a semi-analytic model of galaxy formation and evolution. Such a modelling has been quite successful in reproducing the optical properties of galaxies. We assume hereafter the high-redshift damped Lyman-$\alpha$ (DLA) systems to be the progenitors of present day galaxies, and we design a series of models which are consistent with the evolution of cosmic comoving emissivities in the available near infrared (NIR), optical, ultraviolet (UV), and far infrared (FIR) bands along with the evolution of the neutral hydrogen content and average metallicity of damped Lyman-$\alpha$ systems (DLA). We use these models to compute the galactic contribution to the Lyman-limit emissivity and background flux for $0 \simeq z \le 4$. We take into account the absorption of Lyman-limit photons by HI and dust in the interstellar medium (ISM) of the galaxies. We find that the background Lyman-limit flux due to galaxies might dominate (or be comparable to) the contribution from quasars at almost all redshifts if the absorption by HI in the ISM is neglected. The ISM HI absorption results in a severe diminishing of this flux--by almost three orders of magnitude at high redshifts to between one and two orders at $z \simeq 0$. Though the resulting galaxy flux is completely negligible at high redshifts, it is comparable to the quasar flux at $z \simeq 0$.Comment: 14 pages, 5 figures, requires mn.sty, accepted for publication in MNRA

Pharmacological utilization of bergamottin, derived from grapefruits, in cancer prevention and therapy

In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This has led to several studies evaluating the possible application of natural agents found in vegetables, fruits, or plant-derived products that may be useful for cancer treatment. Bergamottin is a furanocoumarin derived from grapefruits and is also a well-known cytochrome P450 inhibitor. Recent studies have demonstrated potent anti-oxidative, anti-inflammatory, and anti-cancer properties of grapefruit furanocoumarin both in vitro and in vivo. The present review focuses on the potential anti-neoplastic effects of bergamottin in different tumor models and briefly describes the molecular targets affected by this agent

Molecular Imaging of Petroleum Asphaltenes by Scanning Tunneling Microscopy: Verification of Structure from 13C and Proton Nuclear Magnetic Resonance Data

Scanning tunneling microscopy (STM) was used to verify the molecular structure of Maya asphaltene which had been derived from combined 13C and proton nuclear magnetic resonance (NMR) experiments. Petroleum asphaltenes are known to contain large polynuclear aromatic centers with aliphatic sidechains. Average molecular models of Maya asphaltenes were derived using studies which included combined proton and 13C NMR data to determine total aromatic carbon content and the ratio of peripheral to internal aromatic ring carbons. These parameters permitted estimating the average number of aromatic rings per condensed cluster. These Maya asphaltenes were imaged by scanning tunneling microscopy (STM) in a dilute solution of tetrahydrofuran on highly oriented pyrolytic graphite. The sizes and structures of the asphaltenes as observed by STM are in reasonable agreement with these average molecular models. We observed asymmetric structures whose largest dimension averaged 10.4 Å ± 1.9 Å from 24 separate images. The condensed ring portions of three representative NMR derived molecular models yielded an average dimension of 11.1 Å ± 1.4 Å

Potential anti-inflammatory and anti-cancer properties of farnesol

© 2018 by the authors. Farnesol, an acyclic sesquiterpene alcohol, is predominantly found in essential oils of various plants in nature. It has been reported to exhibit anti-cancer and anti-inflammatory effects, and also alleviate allergic asthma, gliosis, and edema. In numerous tumor cell lines, farnesol can modulate various tumorigenic proteins and/or modulates diverse signal transduction cascades. It can also induce apoptosis and downregulate cell proliferation, angiogenesis, and cell survival. To exert its anti-inflammatory/anti-oncogenic effects, farnesol can modulate Ras protein and nuclear factor kappa-light-chain-enhancer of activated B cells activation to downregulate the expression of various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin-6. In this review, we describe the potential mechanisms of action underlying the therapeutic effects of farnesol against cancers and inflammatory disorders. Furthermore, these findings support the clinical development of farnesol as a potential pharmacological agent in clinical studies

Molecular targets modulated by fangchinoline in tumor cells and preclinical models

© 2018 MDPI AG. All rights reserved. Despite tremendous progress made during the last few decades in the treatment options for cancer, compounds isolated from Mother Nature remain the mainstay for therapy of various malignancies. Fangchinoline, initially isolated from the dried root of Stephaniae tetrandrine, has been found to exhibit diverse pharmacological effects including significant anticancer activities both in tumor cell lines and selected preclinical models. This alkaloid appears to act by modulating the activation of various important oncogenic molecules involved in tumorigenesis leading to a significant decrease in aberrant proliferation, survival and metastasis of tumor cells. This mini-review briefly describes the potential effects of fangchinoline on important hallmarks of cancer and highlights the molecular targets modulated by this alkaloid in various tumor cell lines and preclinical models

11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle

OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer$^{307}$ insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer$^{307}$ IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer$^{307}$ IRS1 decreased and pThr$^{308}$ Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer$^{307}$ IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer$^{307}$ IRS1, increases pThr$^{308}$ Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action

Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

This paper was originally published in PLOS ONE (Robinson KA, Hegyi K, Hannun YA, Buse MG, Sethi JK, PLoS ONE 2014, 9(10): e108963. doi:10.1371/journal.pone.0108963).Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (David Phillips Fellowship, JF16994), Diabetes UK (BDA:RD06/0003237) and British Heart Foundation (PG/10/38/28359) to J.K. Sethi and also from National Institute of Diabetes and Digestive and Kidney Diseases (DK-02001) to M.G. Buse

Factors influencing the likelihood of acceptance of postpartum intrauterine devices across four countries: India, Nepal, Sri Lanka, and Tanzania.

OBJECTIVE: To examine the factors that positively influenced the likelihood of accepting provision of postpartum intrauterine devices (PPIUDs) across four countries: Sri Lanka, Nepal, Tanzania, and India. METHODS: Healthcare providers were trained across 24 facilities in counselling and insertion of PPIUDs as part of a large multicountry study. Women delivered were asked to take part in a 15-minute face-to-face structured interview conducted by in-country data collection officers prior to discharge. Univariate analysis was performed to investigate factors associated with acceptance. RESULTS: From January 2016 to November 2017, 6477 health providers were trained, 239 033 deliveries occurred, and 219 242 interviews were conducted. Of those interviewed, 68% were counselled on family planning and 56% on PPIUD, with 20% consenting to PPIUD. Multiple counselling sessions was the only factor resulting in higher consent rates (OR 1.30-1.39) across all countries. Odds ratios for women's age, parity, and cadre of provider counselling varied between countries. CONCLUSION: Consent for contraception, specifically PPIUD, is such a culturally specific topic and generalization across countries is not possible. When planning contraceptive policy changes, it is important to have an understanding of the sociocultural factors at play