Heterogeneous grain-scale response in ferroic polycrystals under electric field

Understanding coupling of ferroic properties over grain boundaries and within clusters of grains in polycrystalline materials is hindered due to a lack of direct experimental methods to probe the behaviour of individual grains in the bulk of a material. Here, a variant of three-dimensional X-ray diffraction (3D-XRD) is used to resolve the non-180?? ferroelectric domain switching strain components of 191 grains from the bulk of a polycrystalline electro-ceramic that has undergone an electric-field-induced phase transformation. It is found that while the orientation of a given grain relative to the field direction has a significant influence on the phase and resultant domain texture, there are large deviations from the average behaviour at the grain scale. It is suggested that these deviations arise from local strain and electric field neighbourhoods being highly heterogeneous within the bulk polycrystal. Additionally, the minimisation of electrostatic potentials at the grain boundaries due to interacting ferroelectric domains must also be considered. It is found that the local grain-scale deviations average out over approximately 10-20 grains. These results provide unique insight into the grain-scale interactions of ferroic materials and will be of value for future efforts to comprehensively model these and related materials at that length-scaleopen

BMN vacua, superstars and non-abelian T-duality

Acting with non-Abelian T-duality on the $S^3$ inside the $AdS_5$ subspace of $AdS_5\times S^5$ with $N$ units of flux, we generate a new half-BPS solution with $SU(2|4)$ symmetry that belongs to the Lin-Lunin-Maldacena class of geometries. The analysis of the asymptotics, quantised charges and probe branes in this geometry suggests an interpretation as the gravity dual to the Berenstein-Maldacena-Nastase Plane Wave Matrix Model, in a particular vacuum associated to a partition of $N$, in which the multiplicity of each $SU(2)$ irreducible representation is equal to its dimension. This vacuum is interpreted in M-theory in terms of giant gravitons backreacting in the maximally supersymmetric pp-wave geometry. Consistently with this, we show that the non-Abelian T-dual solution exactly agrees with the Penrose limit of the superstar solution in $AdS_7\times S^4$. This suggests an interesting global completion of the non-Abelian T-dual solution in terms of an M5-brane geometry.Comment: 28 pages, discussion in section 5.1 improved, results unchanged, reference added. Matches published versio

Kinetic Analysis of Substrate Utilization by Native and TNAP-, NPP1-, or PHOSPHO1-Deficient Matrix Vesicles

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Here, we have studied phosphosubstrate catalysis by osteoblast-derived MVs at physiologic pH, analyzing the hydrolysis of ATP, ADP, and PPi by isolated wild-type (WT) as well as TNAP-, NPP1- and PHOSPHO1-deficient MVs. Comparison of the catalytic efficiencies identified ATP as the main substrate hydrolyzed by WT MVs. The lack of TNAP had the most pronounced effect on the hydrolysis of all physiologic substrates. The lack of PHOSPHO1 affected ATP hydrolysis via a secondary reduction in the levels of TNAP in PHOSPHO1-deficient MVs. The lack of NPP1 did not significantly affect the kinetic parameters of hydrolysis when compared with WT MVs for any of the substrates. We conclude that TNAP is the enzyme that hydrolyzes both ATP and PPi in the MV compartment. NPP1 does not have a major role in PPi generation from ATP at the level of MVs, in contrast to its accepted role on the surface of the osteoblasts and chondrocytes, but rather acts as a phosphatase in the absence of TNAP. © 2010 American Society for Bone and Mineral Research

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion.</p> <p>Methods</p> <p>Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI).</p> <p>Results</p> <p>A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9).</p> <p>Conclusions</p> <p>A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.</p

Factors Associated with Adherence to Treatment with Isoniazid for the Prevention of Tuberculosis amongst People Living with HIV/AIDS: A Systematic Review of Qualitative Data

Objective To systematically identify from qualitative data in the published literature the main barriers to adherence to isoniazid preventive therapy (IPT) for tuberculosis (TB) among people living with HIV/AIDS (PLWHA). Methods We searched ten data sources, including MEDLINE and EMBASE for articles published in peer-reviewed journals from inception through to December 2011 for evidence relevant to IPT for TB in relation to PLWHA. Studies were assessed for quality using the CASP critical appraisal tool for qualitative studies. Data extracted from studies were then analysed thematically using thematic synthesis. Results Eight studies, two of which were conducted within the same clinical trial, met the inclusion criteria. In addition to the influence of personal characteristics, five overarching themes were identified: Individual personal beliefs; HIV treatment and related issues; Socio-economic factors; Family and other social support factors, and Relationships with health providers. The review confirms current understanding of adherence to treatment as influenced by patients' understanding of, and beliefs related to treatment regimens. This is in-turn influenced by broader factors, namely: socio-economic factors such as poverty and lack of health facilities; the level of support available to patients from family and other networks and the stigma that emanates from these relationships; and relationships with health providers, which in-turn become a delicate issue given the sensitivity of dealing with two chronic diseases of significant morbidity and mortality toll. HIV treatment related issues also influence adherence to IPT, whereby challenges related to the acceptance, organisation and administration of these two long-term treatment regimens and stigma related to HIV/AIDS, are seen to be major factors. Conclusion Understanding this complex interplay of factors more clearly is essential for healthcare decision-makers to be able to achieve the level of adherence required to effectively mitigate the threat posed by co-infection with TB and HIV/AIDS in developing countries

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field