Vitamin B12

What is vitamin B12? Vitamin B12 (cobalamin) is a water soluble vitamin required for several physiological processes, including normal nervous system functioning, and red blood cell development and maturation. It has antioxidant effects, is a co-factor in mitochondrial energy metabolism, and contributes to DNA synthesis, the methylation cycle, and epigenetic regulation. 1 2 B12 is present in foods of animal origin, such as meat, eggs, and milk, or via food fortification. Healthy adults require an average intake of 4-7 mcg daily to maintain B12 status. 3 4 Indications for B12 treatment, administration routes, and preparations Treatment with B12 may be required for a variety of reasons (table 1).</p

In vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine.

Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a >3-fold and >2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo

Network Hawkes Process Models for Exploring Latent Hierarchy in Social Animal Interactions

Group-based social dominance hierarchies are of essential interest in animal behavior research. Studies often record aggressive interactions observed over time, and models that can capture such dynamic hierarchy are therefore crucial. Traditional ranking methods summarize interactions across time, using only aggregate counts. Instead, we take advantage of the interaction timestamps, proposing a series of network point process models with latent ranks. We carefully design these models to incorporate important characteristics of animal interaction data, including the winner effect, bursting and pair-flip phenomena. Through iteratively constructing and evaluating these models we arrive at the final cohort Markov-Modulated Hawkes process (C-MMHP), which best characterizes all aforementioned patterns observed in interaction data. We compare all models using simulated and real data. Using statistically developed diagnostic perspectives, we demonstrate that the C-MMHP model outperforms other methods, capturing relevant latent ranking structures that lead to meaningful predictions for real data

Thermal aspects of a low cost power electronic converter for high capacity, smart residential distribution networks

A key challenge facing the UK Distribution Network Operators (DNOs) today is the increasing demand for power being placed on residential networks. Also, the increase in distributed generation (DG) is now resulting in unacceptable local voltage rises and power quality issues. A cost effective solution to these problems can be achieved on the existing infrastructure by increasing the local network phase voltage to 400 V and stepping back down to 230 V at each house, using a DNO-owned, voltage regulated power electronic converter (PEC). The thermal and protection issues associated with the design of such a PEC, which is to be installed in the meterbox of each property, are discussed in this paper

The health and well-being effects of drought: Assessing multi-stakeholder perspectives through narratives from the UK

The global literature on drought and health highlights a variety of health effects for people in developing countries where certain prevailing social, economic and environmental conditions increase their vulnerability especially with climate change. Despite increased focus on climate change, relatively less is known about the health-drought impacts in the developed country context. In the UK, where climate change–related risk of water shortages has been identified as a key area for action, there is need for better understanding of drought-health linkages. This paper assesses people’s narratives of drought on health and well-being in the UK using a source-receptor-impact framing. Stakeholder narratives indicate that drought can present perceived health and well-being effects through reduced water quantity, water quality, compromised hygiene and sanitation, food security, and air quality. Heatwave associated with drought was also identified as a source of health effects through heat and wildfire, and drought-related vectors. Drought was viewed as potentially attributing both negative and positive effects for physical and mental health, with emphasis on mental health. Health impacts were often complex and cross-sectoral in nature indicating the need for a management approach across several sectors that targets drought and health in risk assessment and adaptation planning processes. Two recurring themes in the UK narratives were the health consequences of drought for ‘at-risk’ groups and the need to target them, and that drought in a changing climate presented potential health implications for at-risk groups

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity

The opportunistic human pathogen, Pseudomonas aeruginosa, is a major cause of infections in chronic wounds, burns and the lungs of cystic fibrosis patients. The P. aeruginosa genome encodes at least three proteins exhibiting the characteristic three domain structure of autotransporters, but much remains to be understood about the functions of these three proteins and their role in pathogenicity. Autotransporters are the largest family of secreted proteins in Gram-negative bacteria, and those characterised are virulence factors. Here, we demonstrate that the PA0328 autotransporter is a cell-surface tethered, arginine-specific aminopeptidase, and have defined its active site by site directed mutagenesis. Hence, we have assigned PA0328 with the name AaaA, for arginine-specific autotransporter of P. aeruginosa. We show that AaaA provides a fitness advantage in environments where the sole source of nitrogen is peptides with an aminoterminal arginine, and that this could be important for establishing an infection, as the lack of AaaA led to attenuation in a mouse chronic wound infection which correlated with lower levels of the cytokines TNFα, IL-1α, KC and COX-2. Consequently AaaA is an important virulence factor playing a significant role in the successful establishment of P. aeruginosa infections

An Unusual Radio Galaxy in Abell 428: A Large, Powerful FR I Source in a Disk-Dominated Host

We report the discovery of a powerful (~10^{24} Watts/Hz) FR I radio source in a highly flattened disk-dominated galaxy. Half of the radio flux from this source is concentrated within the host galaxy, with the remainder in a pair of nearly symmetrical lobes with total extent ~200kpc nearly perpendicular to the disk. The traditional wisdom maintains that powerful, extended radio sources are found only in ellipticals or recent merger events. We report B,R,J, and K imaging, optical spectroscopy, a rotation curve, an IRAS detection, and a VLA 20cm image for this galaxy, 0313-192. The optical and NIR images clearly show a disk. We detect apparent spiral arms and a dust-lane from B band imaging. The reddened nucleus is consistent with extinction by a similar dust-lane. The optical spectrum suggests a central AGN and some evidence of a starburst, with both the AGN and central starlight appearing substantially reddened. From analysis of the extended line emission in [OIII] and H-alpha we derive a rotation curve consistent with an early- type, dusty spiral seen edge-on. From the IRAS detection at 60 and 100 microns, we find that the ratio of Far IR to radio flux places this object firmly as a radio galaxy (i.e. the radio emission is not powered by star formation). The radio structure suggests that the radio source in this galaxy is related to the same physical mechanisms present in jet-fed powerful radio sources, and that such powerful, extended sources can (albeit extremely rarely) occur in a disk-dominated host.Comment: 30 pages LaTeX, 1 table, 8 postscript figures. Accepted for publication in the Astrophysical Journa