Ground States of Two-Dimensional Polyampholytes

We perform an exact enumeration study of polymers formed from a (quenched) random sequence of charged monomers $\pm q_0$, restricted to a 2-dimensional square lattice. Monomers interact via a logarithmic (Coulomb) interaction. We study the ground state properties of the polymers as a function of their excess charge $Q$ for all possible charge sequences up to a polymer length N=18. We find that the ground state of the neutral ensemble is compact and its energy extensive and self-averaging. The addition of small excess charge causes an expansion of the ground state with the monomer density depending only on $Q$. In an annealed ensemble the ground state is fully stretched for any excess charge $Q>0$.Comment: 6 pages, 6 eps figures, RevTex, Submitted to Phys. Rev.

Generalizing the O(N)-field theory to N-colored manifolds of arbitrary internal dimension D

We introduce a geometric generalization of the O(N)-field theory that describes N-colored membranes with arbitrary dimension D. As the O(N)-model reduces in the limit N->0 to self-avoiding polymers, the N-colored manifold model leads to self-avoiding tethered membranes. In the other limit, for inner dimension D->1, the manifold model reduces to the O(N)-field theory. We analyze the scaling properties of the model at criticality by a one-loop perturbative renormalization group analysis around an upper critical line. The freedom to optimize with respect to the expansion point on this line allows us to obtain the exponent \nu of standard field theory to much better precision that the usual 1-loop calculations. Some other field theoretical techniques, such as the large N limit and Hartree approximation, can also be applied to this model. By comparison of low and high temperature expansions, we arrive at a conjecture for the nature of droplets dominating the 3d-Ising model at criticality, which is satisfied by our numerical results. We can also construct an appropriate generalization that describes cubic anisotropy, by adding an interaction between manifolds of the same color. The two parameter space includes a variety of new phases and fixed points, some with Ising criticality, enabling us to extract a remarkably precise value of 0.6315 for the exponent \nu in d=3. A particular limit of the model with cubic anisotropy corresponds to the random bond Ising problem; unlike the field theory formulation, we find a fixed point describing this system at 1-loop order.Comment: 57 pages latex, 26 figures included in the tex

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio

Partially Annealed Disorder and Collapse of Like-Charged Macroions

Charged systems with partially annealed charge disorder are investigated using field-theoretic and replica methods. Charge disorder is assumed to be confined to macroion surfaces surrounded by a cloud of mobile neutralizing counterions in an aqueous solvent. A general formalism is developed by assuming that the disorder is partially annealed (with purely annealed and purely quenched disorder included as special cases), i.e., we assume in general that the disorder undergoes a slow dynamics relative to fast-relaxing counterions making it possible thus to study the stationary-state properties of the system using methods similar to those available in equilibrium statistical mechanics. By focusing on the specific case of two planar surfaces of equal mean surface charge and disorder variance, it is shown that partial annealing of the quenched disorder leads to renormalization of the mean surface charge density and thus a reduction of the inter-plate repulsion on the mean-field or weak-coupling level. In the strong-coupling limit, charge disorder induces a long-range attraction resulting in a continuous disorder-driven collapse transition for the two surfaces as the disorder variance exceeds a threshold value. Disorder annealing further enhances the attraction and, in the limit of low screening, leads to a global attractive instability in the system.Comment: 21 pages, 2 figure

Effects of the fatty acid amide hydrolase inhibitor URB597 on coping behavior under challenging conditions in mice

RATIONALE: Recent evidence suggests that in addition to controlling emotional behavior in general, endocannabinoid signaling is engaged in shaping behavioral responses to challenges. This important function of endocannabinoids is still poorly understood. OBJECTIVES: Here we investigated the impact of blockade of fatty acid amide hydrolase (FAAH), the degrading enzyme of anandamide on behavioral responses induced by challenges of different intensity. METHODS: Mice treated with FAAH inhibitor URB597 were either manually restrained on their backs (back test) or received foot-shocks. RESULTS: The behavior of mice showed bimodal distribution in the back test: they either predominantly showed escape attempts or equally distributed time between passivity and escape. URB597 increased escapes in animals with low escape scores. No effects were noticed in mice showing high escape scores, which is likely due to a ceiling effect. We hypothesized that stronger stressors would wash out individual differences in coping; therefore, we exposed mice to foot-shocks that decreased locomotion and increased freezing in all mice. URB597 ameliorated both responses. The re-exposure of mice to the shock cage 14 days later without delivering shocks or treatment was followed by reduced and fragmented sleep as shown by electrophysiological recordings. Surprisingly, sleep was more disturbed after the reminder than after shocks in rats receiving vehicle before foot-shocks. These reminder-induced disturbances were abolished by URB597 administered before shocks. CONCLUSIONS: These findings suggest that FAAH blockade has an important role in the selection of behavioral responses under challenging conditions and-judging from its long-term effects-that it influences the cognitive appraisal of the challenge

AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD

HIV-1 pol Diversity among Female Bar and Hotel Workers in Northern Tanzania

A national ART program was launched in Tanzania in October 2004. Due to the existence of multiple HIV-1 subtypes and recombinant viruses co-circulating in Tanzania, it is important to monitor rates of drug resistance. The present study determined the prevalence of HIV-1 drug resistance mutations among ART-naive female bar and hotel workers, a high-risk population for HIV-1 infection in Moshi, Tanzania. A partial HIV-1 pol gene was analyzed by single-genome amplification and sequencing in 45 subjects (622 pol sequences total; median number of sequences per subject, 13; IQR 5–20) in samples collected in 2005. The prevalence of HIV-1 subtypes A1, C, and D, and inter-subtype recombinant viruses, was 36%, 29%, 9% and 27%, respectively. Thirteen different recombination patterns included D/A1/D, C/A1, A1/C/A1, A1/U/A1, C/U/A1, C/A1, U/D/U, D/A1/D, A1/C, A1/C, A2/C/A2, CRF10_CD/C/CRF10_CD and CRF35_AD/A1/CRF35_AD. CRF35_AD was identified in Tanzania for the first time. All recombinant viruses in this study were unique, suggesting ongoing recombination processes among circulating HIV-1 variants. The prevalence of multiple infections in this population was 16% (n = 7). Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). In some subjects, polymorphisms were observed at the RT positions 41, 69, 75, 98, 101, 179, 190, and 215. Secondary mutations associated with NNRTIs were observed at the RT positions 90 (7%) and 138 (6%). In the protease gene, three subjects (7%) had M46I/L mutations. All subjects in this study had HIV-1 subtype-specific natural polymorphisms at positions 36, 69, 89 and 93 that are associated with drug resistance in HIV-1 subtype B. These results suggested that HIV-1 drug resistance mutations and natural polymorphisms existed in this population before the initiation of the national ART program. With increasing use of ARV, these results highlight the importance of drug resistance monitoring in Tanzania

A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens

Bringing analysis of gender and social–ecological resilience together in small-scale fisheries research: Challenges and opportunities

The demand for gender analysis is now increasingly orthodox in natural resource programming, including that for small-scale fisheries. Whilst the analysis of social–ecological resilience has made valuable contributions to integrating social dimensions into research and policy-making on natural resource management, it has so far demonstrated limited success in effectively integrating considerations of gender equity. This paper reviews the challenges in, and opportunities for, bringing a gender analysis together with social–ecological resilience analysis in the context of small-scale fisheries research in developing countries. We conclude that rather than searching for a single unifying framework for gender and resilience analysis, it will be more effective to pursue a plural solution in which closer engagement is fostered between analysis of gender and social-ecological resilience whilst preserving the strengths of each approach. This approach can make an important contribution to developing a better evidence base for small-scale fisheries management and policy

Expert consensus document: A 'diamond' approach to personalized treatment of angina.

In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for traditional first-choice drugs. Considering some drugs, but not others, to be first choice is, therefore, difficult. Moreover, double or triple therapy is often needed to control angina. Patients with angina can have several comorbidities, and symptoms can result from various underlying pathophysiologies. Some agents, in addition to having antianginal effects, have properties that could be useful depending on the comorbidities present and the mechanisms of angina, but the guidelines do not provide recommendations on the optimal combinations of drugs. In this Consensus Statement, we propose an individualized approach to angina treatment, which takes into consideration the patient, their comorbidities, and the underlying mechanism of disease