Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH

Subdiffusion and weak ergodicity breaking in the presence of a reactive boundary

We derive the boundary condition for a subdiffusive particle interacting with a reactive boundary with finite reaction rate. Molecular crowding conditions, that are found to cause subdiffusion of larger molecules in biological cells, are shown to effect long-tailed distributions with identical exponent for both the unbinding times from the boundary to the bulk and the rebinding times from the bulk. This causes a weak ergodicity breaking: typically, an individual particle either stays bound or remains in the bulk for very long times. We discuss why this may be beneficial for in vivo gene regulation by DNA-binding proteins, whose typical concentrations are nanomolarComment: 4 pages, 1 figure, REVTeX4, accepted to Phys Rev Lett, some typos correcte

Repeated Parallel Evolution of Parental Care Strategies within Xenotilapia, a Genus of Cichlid Fishes from Lake Tanganyika

The factors promoting the evolution of parental care strategies have been extensively studied in experiment and theory. However, most attempts to examine parental care in an evolutionary context have evaluated broad taxonomic categories. The explosive and recent diversifications of East African cichlid fishes offer exceptional opportunities to study the evolution of various life history traits based on species-level phylogenies. The Xenotilapia lineage within the endemic Lake Tanganyika cichlid tribe Ectodini comprises species that display either biparental or maternal only brood care and hence offers a unique opportunity to study the evolution of distinct parental care strategies in a phylogenetic framework. In order to reconstruct the evolutionary relationships among 16 species of this lineage we scored 2,478 Amplified Fragment Length Polymorphisms (AFLPs) across the genome. We find that the Ectodini genus Enantiopus is embedded within the genus Xenotilapia and that during 2.5 to 3 million years of evolution within the Xenotilapia clade there have been 3–5 transitions from maternal only to biparental care. While most previous models suggest that uniparental care (maternal or paternal) arose from biparental care, we conclude from our species-level analysis that the evolution of parental care strategies is not only remarkably fast, but much more labile than previously expected

Continuity properties of measurable group cohomology

A version of group cohomology for locally compact groups and Polish modules has previously been developed using a bar resolution restricted to measurable cochains. That theory was shown to enjoy analogs of most of the standard algebraic properties of group cohomology, but various analytic features of those cohomology groups were only partially understood. This paper re-examines some of those issues. At its heart is a simple dimension-shifting argument which enables one to `regularize' measurable cocycles, leading to some simplifications in the description of the cohomology groups. A range of consequences are then derived from this argument. First, we prove that for target modules that are Fr\'echet spaces, the cohomology groups agree with those defined using continuous cocycles, and hence they vanish in positive degrees when the acting group is compact. Using this, we then show that for Fr\'echet, discrete or toral modules the cohomology groups are continuous under forming inverse limits of compact base groups, and also under forming direct limits of discrete target modules. Lastly, these results together enable us to establish various circumstances under which the measurable-cochains cohomology groups coincide with others defined using sheaves on a semi-simplicial space associated to the underlying group, or sheaves on a classifying space for that group. We also prove in some cases that the natural quotient topologies on the measurable-cochains cohomology groups are Hausdorff.Comment: 52 pages. [Nov 22, 2011:] Major re-write with Calvin C. Moore as new co-author. Results from previous version strengthened and several new results added. [Nov 25, 2012:] Final version now available at springerlink.co

Variations in Concentrations and Compositions of Polycyclic Aromatic Hydrocarbons (PAHs) in Coals Related to the Coal Rank and Origin

The release of unburnt coal particles and associated polycyclic aromatic hydrocarbons (PAHs) may cause adverse impacts on the environment. This study assessed variations in the concentration and composition of PAHs in a set of fifty coal samples from eleven coal basins worldwide. The maximum PAH concentrations at high volatile bituminous rank were recorded in samples from a single basin. Considering the entire sample, the highest PAH concentrations were in fact found outside of this rank range, suggesting that the maceral composition and thus the coal\u27s origin also influenced PAH concentrations. The examination of the PAH compositions revealed that alkylated 2-3 ring PAHs remain dominant compounds irrespective of coal rank or origin. Multivariate analysis based on PAH and maceral content, bulk and maturity parameters allowed the recognition of seven groups with different rank and origin within the coal sample set

A comparative study of additive manufacturing techniques: Residual stress and microstructural analysis of CLAD and WAAM printed Ti-6Al-4V components

Nowadays, there is a great manufacturing trend in producing higher quality net-shape components of challenging geometries. One of the major challenges faced by additive manufacturing (AM) is the residual stresses generated during AM part fabrication often leading to unacceptable distortions and degradation of mechanical properties. Therefore, gaining insight into residual strain/stress distribution is essential for ensuring acceptable quality and performance of high-tech AM parts. This research is aimed at comparing microstructure and residual stress built-up in Ti–6Al–4V AM components produced by Wire + Arc Additive Manufacturing (WAAM) and by laser cladding process (CLAD)

Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men