Vertebral Bone Mineral Measures and Psychological Wellbeing Among Individuals with Modic Changes

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Self-field effects upon the critical current density of flat superconducting strips

We develop a general theory to account self-consistently for self-field effects upon the average transport critical current density Jc of a flat type-II superconducting strip in the mixed state when the bulk pinning is characterized by a field-dependent depinning critical current density Jp(B), where B is the local magnetic flux density. We first consider the possibility of both bulk and edge-pinning contributions but conclude that bulk pinning dominates over geometrical edge-barrier effects in state-of-the-art YBCO films and prototype second-generation coated conductors. We apply our theory using the Kim model, JpK(B) = JpK(0)/(1+|B|/B0), as an example. We calculate Jc(Ba) as a function of a perpendicular applied magnetic induction Ba and show how Jc(Ba) is related to JpK(B). We find that Jc(Ba) is very nearly equal to JpK(Ba) when Ba > Ba*, where Ba* is the value of Ba that makes the net flux density zero at the strip's edge. However, Jc(Ba) is suppressed relative to JpK(Ba) at low fields when Ba < Ba*, with the largest suppression occurring when Ba*/B0 is of order unity or larger.Comment: 9 pages, 4 figures, minor revisions to add four reference

The Future of U.S. Natural Gas Production, Use, and Trade

Abstract and PDF report are also available on the MIT Joint Program on the Science and Policy of Global Change website (http://globalchange.mit.edu/)Two computable general equilibrium models, one global and the other providing U.S. regional detail, are applied to analysis of the future of U.S. natural gas as an input to an MIT study of the topic. The focus is on uncertainties including the scale and cost of gas resources, the costs of competing technologies, the pattern of greenhouse gas mitigation, and the evolution of global natural gas markets. Results show that the outlook for gas over the next several decades is very favorable. In electric generation, given the unproven and relatively high cost of other low-carbon generation alternatives, gas likely is the preferred alternative to coal. A broad GHG pricing policy would increase gas use in generation but reduce use in other sectors, on a balance increasing its role from present levels. The shale gas resource is a major contributor to this optimistic view of the future of gas, but it is far from a panacea over the longer term. Gas can be an effective bridge to a lower emissions future, but investment in the development of still lower CO2 technologies remains an important priority. Also, international gas resources may well prove to be less costly than those in the U.S., except for the lowest-cost domestic shale resources, and the emergence of an integrated global gas market could result in significant U.S. gas imports.American Clean Skies Foundation, with additional support from the Hess Corporation, the Agencia Nacional de Hidrocarburos (Columbia), the Energy Futures Coalition, and the MIT Energy Initiative

Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas

This article is available open access through the publisher’s website. Copyright @ 2009 The Authors.Background - Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma. Methods - We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription–polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided. Results - Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026). Conclusions - We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.Sport Aiding Medical Research for Kids (SPARKS), Great Ormond Street Hospital/National Health Service, the National Cancer Institute and University of Parma

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD

Lysosome-mediated processing of chromatin in senescence

Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression

The XMM Cluster Survey: The interplay between the brightest cluster galaxy and the intra-cluster medium via AGN feedback

Using a sample of 123 X-ray clusters and groups drawn from the XMM-Cluster Survey first data release, we investigate the interplay between the brightest cluster galaxy (BCG), its black hole, and the intra-cluster/group medium (ICM). It appears that for groups and clusters with a BCG likely to host significant AGN feedback, gas cooling dominates in those with Tx > 2 keV while AGN feedback dominates below. This may be understood through the sub-unity exponent found in the scaling relation we derive between the BCG mass and cluster mass over the halo mass range 10^13 < M500 < 10^15Msol and the lack of correlation between radio luminosity and cluster mass, such that BCG AGN in groups can have relatively more energetic influence on the ICM. The Lx - Tx relation for systems with the most massive BCGs, or those with BCGs co-located with the peak of the ICM emission, is steeper than that for those with the least massive and most offset, which instead follows self-similarity. This is evidence that a combination of central gas cooling and powerful, well fuelled AGN causes the departure of the ICM from pure gravitational heating, with the steepened relation crossing self-similarity at Tx = 2 keV. Importantly, regardless of their black hole mass, BCGs are more likely to host radio-loud AGN if they are in a massive cluster (Tx > 2 keV) and again co-located with an effective fuel supply of dense, cooling gas. This demonstrates that the most massive black holes appear to know more about their host cluster than they do about their host galaxy. The results lead us to propose a physically motivated, empirical definition of 'cluster' and 'group', delineated at 2 keV.Comment: Accepted for publication in MNRAS - replaced to match corrected proo

Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis

Early-life stress is an established risk for the development of psychiatric disorders. Post-weaning isolation rearing of rats produces lasting developmental changes in behavior and brain function that may have translational pathophysiological relevance to alterations seen in schizophrenia, but the underlying mechanisms are unclear. Accumulating evidence supports the premise that gut microbiota influence brain development and function by affecting inflammatory mediators, the hypothalamic-pituitary-adrenal axis and neurotransmission, but there is little knowledge of whether the microbiota-gut-brain axis might contribute to the development of schizophrenia-related behaviors. To this end the effects of social isolation (SI; a well-validated animal model for schizophrenia)-induced changes in rat behavior were correlated with alterations in gut microbiota, hippocampal neurogenesis and brain cytokine levels. Twenty-four male Lister hooded rats were housed in social groups (group-housed, GH, 3 littermates per cage) or alone (SI) from weaning (post-natal day 24) for four weeks before recording open field exploration, locomotor activity/novel object discrimination (NOD), elevated plus maze, conditioned freezing response (CFR) and restraint stress at one week intervals. Post-mortem caecal microbiota composition, cortical and hippocampal cytokines and neurogenesis were correlated to indices of behavioral changes. SI rats were hyperactive in the open field and locomotor activity chambers traveling further than GH controls in the less aversive peripheral zone. While SI rats showed few alterations in plus maze or NOD they froze for significantly less time than GH following conditioning in the CFR paradigm, consistent with impaired associative learning and memory. SI rats had significantly fewer BrdU/NeuN positive cells in the dentate gyrus than GH controls. SI rats had altered microbiota composition with increases in Actinobacteria and decreases in the class Clostridia compared to GH controls. Differences were also noted at genus level. Positive correlations were seen between microbiota, hippocampal IL-6 and IL-10, conditioned freezing and open field exploration. Adverse early-life stress resulting from continuous SI increased several indices of ‘anxiety-like’ behavior and impaired associative learning and memory accompanied by changes to gut microbiota, reduced hippocampal IL-6, IL-10 and neurogenesis. This study suggests that early-life stress may produce long-lasting changes in gut microbiota contributing to development of abnormal neuronal and endocrine function and behavior which could play a pivotal role in the aetiology of psychiatric illness