Finite temperature effective action, AdS_5 black holes, and 1/N expansion

We propose a phenomenological matrix model to study string theory in AdS_5 \times S_5 in the canonical ensemble. The model reproduces all the known qualitative features of the theory. In particular, it gives a simple effective potential description of Euclidean black hole nucleation and the tunnelling between thermal AdS and the big black hole. It also has some interesting predictions. We find that there exists a critical temperature at which the Euclidean small black hole undergoes a Gross-Witten phase transition. We identify the phase transition with the Horowitz-Polchinski point where the black hole horizon size becomes comparable to the string scale. The appearance of the Hagedorn divergence of thermal AdS is due to the merger of saddle points corresponding to the Euclidean small black hole and thermal AdS. The merger can be described in terms of a cusp (A_3) catastrophe and divergences at the perturbative string level are smoothed out at finite string coupling using standard techniques of catastrophe theory.Comment: 41 pages, 3 eps figures, uses harvma

Trace Elements Affect Methanogenic Activity and Diversity in Enrichments from Subsurface Coal Bed Produced Water

Microbial methane from coal beds accounts for a significant and growing percentage of natural gas worldwide. Our knowledge of physical and geochemical factors regulating methanogenesis is still in its infancy. We hypothesized that in these closed systems, trace elements (as micronutrients) are a limiting factor for methanogenic growth and activity. Trace elements are essential components of enzymes or cofactors of metabolic pathways associated with methanogenesis. This study examined the effects of eight trace elements (iron, nickel, cobalt, molybdenum, zinc, manganese, boron, and copper) on methane production, on mcrA transcript levels, and on methanogenic community structure in enrichment cultures obtained from coal bed methane (CBM) well produced water samples from the Powder River Basin, Wyoming. Methane production was shown to be limited both by a lack of additional trace elements as well as by the addition of an overly concentrated trace element mixture. Addition of trace elements at concentrations optimized for standard media enhanced methane production by 37%. After 7 days of incubation, the levels of mcrA transcripts in enrichment cultures with trace element amendment were much higher than in cultures without amendment. Transcript levels of mcrA correlated positively with elevated rates of methane production in supplemented enrichments (R2 = 0.95). Metabolically active methanogens, identified by clone sequences of mcrA mRNA retrieved from enrichment cultures, were closely related to Methanobacterium subterraneum and Methanobacterium formicicum. Enrichment cultures were dominated by M. subterraneum and had slightly higher predicted methanogenic richness, but less diversity than enrichment cultures without amendments. These results suggest that varying concentrations of trace elements in produced water from different subsurface coal wells may cause changing levels of CBM production and alter the composition of the active methanogenic community

Multi-year school-based implementation and student outcomes of an evidence-based risk reduction intervention

Background Intervention effects observed in efficacy trials are rarely replicated when the interventions are broadly disseminated, underscoring the need for more information about factors influencing real-life implementation and program impact. Using data from the ongoing national implementation of an evidence-based HIV prevention program [Focus on Youth in The Caribbean (FOYC)] in The Bahamas, this study examines factors influencing teachers’ patterns of implementation, the impact of teachers’ initial implementation of FOYC, and subsequent delivery of the booster sessions on students’ outcomes. Methods Data were collected from the 80 government elementary and 34 middle schools between 2011 and 2014, involving 208 grade 6, 75 grade 7, and 58 grade 8 teachers and 4411 students initially in grade 6 and followed for 3 years. Student outcomes include HIV/AIDS knowledge, reproductive health skills, self-efficacy, and intention to use protection. Data from teachers includes implementation and modification of the curriculum, attitudes towards the prevention program, comfort level with the curriculum, and attendance at training workshops. Structural equation modeling and mixed-effect modeling analyses were applied to examine the impact of teachers’ implementation. Results Teachers’ attitudes towards and comfort with the intervention curriculum, and attendance at the curriculum training workshop had a direct effect on teachers’ patterns of implementation, which had a direct effect on student outcomes. Teachers’ attitudes had a direct positive effect on student outcomes. Teachers’ training in interactive teaching methods and longer duration as teachers were positively associated with teachers’ comfort with the curriculum. High-quality implementation in grade 6 was significantly related to student outcomes in grades 6 and 7 post-implementation. Level of implementation of the booster sessions in grades 7 and 8 were likewise significantly related to subsequent student outcomes in both grades. Conclusions High-quality initial implementation of a prevention program is significantly related to better program outcomes. Poor subsequent delivery of booster sessions can undermine the positive effects from the initial implementation while strong subsequent delivery of booster sessions can partially overcome poor initial implementation

Transient study of the oxygen reduction reaction on reduced Pt and Pt alloys microelectrodes: evidence for the reduction of pre-adsorbed oxygen species linked to dissolved oxygen

Using chronoamperometry at preconditioned oxide-free Pt microdisc electrodes in aqueous media, we investigated the oxygen reduction reaction (ORR) on the millisecond timescale and obtained results consistent with the reduction of oxygen species which adsorb on the electrode before the ORR is electrochemically driven. Furthermore these adsorbed species are clearly linked to oxygen in solution. At long times, the amperometric response is solely controlled by the diffusion of dissolved oxygen towards the microelectrode. However, at short times, typically below 50 ms, the reduction of pre-adsorbed oxygen produces a large extra current whose magnitude depends on the oxygen concentration in solution, deliberate electrode poisoning and the rest time before the potential step. Using sampled current voltammetry we show that this extra current affects the entire potential range of the ORR. Using microdisc electrodes made with Pt alloys we find that the amperometric response is sufficiently sensitive to distinguish oxygen coverage differences between Pt, Pt0.9Rh0.1 and Pt0.9Ir0.1 microdiscs. These unexpected and, to our knowledge, never previously reported results provide new insight into the oxygen reduction reaction on Pt. The existence over a wide potential range of irreversibly adsorbed oxygen species arising from dissolved oxygen and different from Pt oxide is particularly relevant to the development of oxygen reduction catalysts for low temperature fuel cells

CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves

Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1(G93A) transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1(G93A) mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1(G93A) mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease

When Things Are Not as They Appear: Assessing the Adequacy of Cluster Randomization When Outcome Events Are Rare at Baseline

The present study randomly assigned 15 Bahamian elementary schools to one of three intervention conditions. To assess the adequacy of cluster randomization, we examined two concerns identified by the local research team: inequality of gender distribution and environmental risk among groups. Baseline significant differences in risk and protective behaviors were minimal. There were significantly more males in the intervention group. Males had higher rates of risk behavior at all assessments. Poor school performance was also higher among the intervention condition and was significantly associated with increased rates of many but not all risk behaviors. Prior to adjusting for gender and school performance, several risk behaviors appeared to be higher after intervention among intervention youth. Adjusting for gender and school performance eradicated the group differences in risk behavior rates. Results demonstrate the importance of adequate randomization where outcomes of interest are rare events at baseline or differ by gender and there is an unequal gender distribution and the importance of the local research team's knowledge of potential inequalities in environmental risk (i.e., school performance). Not considering such individual differences could impact the integrity of trial outcomes

CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves

Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease

CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves

Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1G93A transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1G93A mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1G93A mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease

The prevalence of cervical cytology abnormalities and human papillomavirus in women infected with the human immunodeficiency virus

<p>Abstract</p> <p>Introduction</p> <p>The human papillomavirus (HPV) is the major etiologic agent in the development of cervical cancer and its natural history of infection is altered in persons infected with the human immunodeficiency virus (HIV). The prevalence of HPV infection and cervical dysplasia in the HIV sero-positive females in the Bahamas is not known. Finding out the prevalence would allow for the establishment of protocols to optimize total care of this population and help prevent morbidity and mortality related to cervical cancer.</p> <p>Objective</p> <p>The Objective of this study is to determine the prevalence of high risk HPV genotypes and the prevalence of cervical dysplasia in the HIV sero-positive females attending the Infectious Disease Clinic at the Princess Margaret Hospital, Nassau, Bahamas.</p> <p>Methods</p> <p>One hundred consecutive, consenting, non-pregnant, HIV-sero-positive females from the Infectious Disease Clinic at the Princess Margaret Hospital in Nassau, Bahamas were screened for high-risk HPV infections and cervical cytology abnormalities using liquid-based pap smear and signal amplification nucleic acid method for HPV detection. A questionnaire was also utilized to gather demographic information and obtain information on known risk factors associated with HPV infections such numbers of partners.</p> <p>Results</p> <p>The prevalence of high-risk HPV was 67% and cervical abnormalities were noted in 44% of the study population. High-risk HPV types were more likely to be present in women with CD4+ cell counts less than 400 μl^-1and in women with cervical cytology abnormalities (97%). The most common cervical abnormality was low-grade squamous intraepithelial lesions.</p> <p>Conclusion</p> <p>Findings suggest that HIV-sero positive females should have HPV testing done as part of their normal gynecology evaluation and these patients should be encouraged and provisions be made for ease of access having regular PAP smears and HPV testing.</p

Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA

Oxazole-containing macrocycles represent a promising class of anticancer agents that target G-quadruplex DNA. We report the results of spectroscopic studies aimed at defining the mode, energetics and specificity with which a hexaoxazole-containing macrocycle (HXDV) binds to the intramolecular quadruplex formed by the human telomeric DNA model oligonucleotide d(T2AG3)4 in the presence of potassium ions. HXDV binds solely to the quadruplex nucleic acid form, but not to the duplex or triplex form. HXDV binds d(T2AG3)4 with a stoichiometry of two drug molecules per quadruplex, with these binding reactions being coupled to the destacking of adenine residues from the terminal G-tetrads. HXDV binding to d(T2AG3)4 does not alter the length of the quadruplex. These collective observations are indicative of a nonintercalative ‘terminal capping’ mode of interaction in which one HXDV molecule binds to each end of the quadruplex. The binding of HXDV to d(T2AG3)4 is entropy driven, with this entropic driving force reflecting contributions from favorable drug-induced alterations in the configurational entropy of the host quadruplex as well as in net hydration. The ‘terminal capping’ mode of binding revealed by our studies may prove to be a general feature of the interactions between oxazole-containing macrocyclic ligands (including telomestatin) and intramolecular DNA quadruplexes