An Exactly Solvable Model for the Integrability-Chaos Transition in Rough Quantum Billiards

A central question of dynamics, largely open in the quantum case, is to what extent it erases a system's memory of its initial properties. Here we present a simple statistically solvable quantum model describing this memory loss across an integrability-chaos transition under a perturbation obeying no selection rules. From the perspective of quantum localization-delocalization on the lattice of quantum numbers, we are dealing with a situation where every lattice site is coupled to every other site with the same strength, on average. The model also rigorously justifies a similar set of relationships recently proposed in the context of two short-range-interacting ultracold atoms in a harmonic waveguide. Application of our model to an ensemble of uncorrelated impurities on a rectangular lattice gives good agreement with ab initio numerics.Comment: 29 pages, 5 figure

Global rates of water-column denitrification derived from nitrogen gas measurements

Biologically available nitrogen (N) limits phytoplankton growth over much of the ocean. The rate at which N is removed from the contemporary ocean by denitrifying bacteria is highly uncertain 1-3. Some studies suggest that N losses exceed inputs 2,4-6; others argue for a balanced budget 3,7,8. Here, we use a global ocean circulation model to simulate the distribution of N 2 gas produced by denitrifying bacteria in the three main suboxic zones in the open ocean. By fitting the model to measured N 2 gas concentrations, we infer a globally integrated rate of water-column denitrification of 66 ±6 Tg N yr -1. Taking into account isotopic constraints on the fraction of denitrification occurring in the water column versus marine sediments, we estimate that the global rate of N loss from marine sediments and the oceanic water column combined amounts to around 230 ±60 Tg N yr -1. Given present estimates of N input rates, our findings imply a net loss of around 20 ± 70 Tg of N from the global ocean each year, indistinguishable from a balanced budget. A balanced N budget, in turn, implies that the marine N cycle is governed by strong regulatory feedbacks. © 2012 Macmillan Publishers Limited. All rights reserved

Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis

MS (multiple sclerosis) is a chronic autoimmune and neurodegenerative pathology of the CNS (central nervous system) affecting approx. 2.5 million people worldwide. Current and emerging DMDs (disease-modifying drugs) predominantly target the immune system. These therapeutic agents slow progression and reduce severity at early stages of MS, but show little activity on the neurodegenerative component of the disease. As the latter determines permanent disability, there is a critical need to pursue alternative modalities. VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating peptide) have potent anti-inflammatory and neuroprotective actions, and have shown significant activity in animal inflammatory disease models including the EAE (experimental autoimmune encephalomyelitis) MS model. Thus, their receptors have become candidate targets for inflammatory diseases. Here, we will discuss the immunomodulatory and neuroprotective actions of VIP and PACAP and their signalling pathways, and then extensively review the structure–activity relationship data and biophysical interaction studies of these peptides with their cognate receptors

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Goal setting and self-efficacy among delinquent, at-risk and not at-risk adolescents

Setting clear achievable goals that enhance self-efficacy and reputational status directs the energies of adolescents into socially conforming or non-conforming activities. This present study investigates the characteristics and relationships between goal setting and self-efficacy among a matched sample of 88 delinquent (18 % female), 97 at-risk (20 % female), and 95 not at-risk adolescents (20 % female). Four hypotheses related to this were tested. Findings revealed that delinquent adolescents reported fewest goals, set fewer challenging goals, had a lower commitment to their goals, and reported lower levels of academic and self-regulatory efficacy than those in the at-risk and not at-risk groups. Discriminant function analysis indicated that adolescents who reported high delinquency goals and low educational and interpersonal goals were likely to belong to the delinquent group, while adolescents who reported high educational and interpersonal goals and low delinquency goals were likely to belong to the not at-risk group. The at-risk and not at-risk groups could not be differentiated. A multinomial logistic regression also revealed that adolescents were more likely to belong to the delinquent group if they reported lower self-regulatory efficacy and lower goal commitment. These findings have important implications for the development of prevention and intervention programs, particularly for those on a trajectory to delinquency. Specifically, programs should focus on assisting adolescents to develop clear self-set achievable goals and support them through the process of attaining them, particularly if the trajectory towards delinquency is to be addressed

From Isotropic to Anisotropic Side Chain Representations: Comparison of Three Models for Residue Contact Estimation

The criterion to determine residue contact is a fundamental problem in deriving knowledge-based mean-force potential energy calculations for protein structures. A frequently used criterion is to require the side chain center-to-center distance or the -to- atom distance to be within a pre-determined cutoff distance. However, the spatially anisotropic nature of the side chain determines that it is challenging to identify the contact pairs. This study compares three side chain contact models: the Atom Distance criteria (ADC) model, the Isotropic Sphere Side chain (ISS) model and the Anisotropic Ellipsoid Side chain (AES) model using 424 high resolution protein structures in the Protein Data Bank. The results indicate that the ADC model is the most accurate and ISS is the worst. The AES model eliminates about 95% of the incorrectly counted contact-pairs in the ISS model. Algorithm analysis shows that AES model is the most computational intensive while ADC model has moderate computational cost. We derived a dataset of the mis-estimated contact pairs by AES model. The most misjudged pairs are Arg-Glu, Arg-Asp and Arg-Tyr. Such a dataset can be useful for developing the improved AES model by incorporating the pair-specific information for the cutoff distance

Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders

Increasing evidence suggests that epigenetic factors have critical roles in gene regulation in neuropsychiatric disorders and in aging, both of which are typically associated with a wide range of gene expression abnormalities. Here, we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated with transcriptionally active chromatin, at the promoter regions of eight schizophrenia-related genes in n=82 postmortem prefrontal cortical samples from normal subjects and those with schizophrenia and bipolar disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with gene expression levels, as measured by real-time qPCR for several genes, including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70 homolog A (TOMM70A) and protein phosphatase 1E (PPM1E). Ac-H3K9K14 levels of several of the genes tested were significantly negatively associated with age in normal subjects and those with bipolar disorder, but not in subjects with schizophrenia, whereby low levels of histone acetylation were observed in early age and throughout aging. Consistent with this observation, significant hypoacetylation of H3K9K14 was detected in young subjects with schizophrenia when compared with age-matched controls. Our results demonstrate that gene expression changes associated with psychiatric disease and aging result from epigenetic mechanisms involving histone acetylation. We further find that treatment with a histone deacetylase (HDAC) inhibitor alters the expression of several candidate genes for schizophrenia in mouse brain. These findings may have therapeutic implications for the clinical use of HDAC inhibitors in psychiatric disorders

Treatment Planning and Volumetric Response Assessment for Yttrium-90 Radioembolization: Semiautomated Determination of Liver Volume and Volume of Tumor Necrosis in Patients with Hepatic Malignancy

PurposeThe primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes.MethodsBetween 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Three observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software.ResultsGood intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472).ConclusionSemiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival