Control of ULF Wave Accessibility to the Inner Magnetosphere by the Convection of Plasma Density

During periods of storm activity and enhanced convection, the plasma density in the afternoon sector of the magnetosphere is highly dynamic due to the development of plasmaspheric drainage plume (PDP) structure. This significantly affects the local Alfvén speed and alters the propagation of ULF waves launched from the magnetopause. Therefore, it can be expected that the accessibility of ULF wave power for radiation belt energization is sensitively dependent on the recent history of magnetospheric convection and the stage of development of the PDP. This is investigated using a 3-D model for ULF waves within the magnetosphere in which the plasma density distribution is evolved using an advection model for cold plasma, driven by a (VollandStern) convection electrostatic field (resulting in PDP structure). The wave model includes magnetic field day/night asymmetry and extends to a paraboloid dayside magnetopause, from which ULF waves are launched at various stages during the PDP development. We find that the plume structure significantly alters the field line resonance location, and the turning point for MHD fast waves, introducing strong asymmetry in the ULF wave distribution across the noon meridian. Moreover, the density enhancement within the PDP creates a waveguide or local cavity for MHD fast waves, such that eigenmodes formed allow the penetration of ULF wave power to much lower L within the plume than outside, providing an avenue for electron energization

Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

The Edinburgh Social Cognition Test (ESCoT):Examining the effects of age on a new measure of theory of mind and social norm understanding

<div><p>Current measures of social cognition have shown inconsistent findings regarding the effects of healthy aging. Moreover, no tests are currently available that allow clinicians and researchers to examine cognitive and affective theory of mind (ToM) and understanding of social norms within the same test. To address these limitations, we present the Edinburgh Social Cognition Test (ESCoT) which assesses cognitive and affective ToM and inter- and intrapersonal understanding of social norms. We examined the effects of age, measures of intelligence and the Broader Autism Phenotype (BAP) on the ESCoT and established tests of social cognition. Additionally, we investigated the convergent validity of the ESCoT based on traditional social cognition measures. The ESCoT was administered alongside Reading the Mind in Films (RMF), Reading the Mind in Eyes (RME), Judgement of Preference and Social Norm Questionnaire to 91 participants (30 aged 18–35 years, 30 aged 45–60 years and 31 aged 65–85 years). Poorer performance on the cognitive and affective ToM ESCoT subtests were predicted by increasing age. The affective ToM ESCoT subtest and RMF were predicted by gender, where being female predicted better performance. Unlike the ESCoT, better performance on the RMF was predicted by higher verbal comprehension and perceptual reasoning abilities, while better performance on the RME was predicted by higher verbal comprehension scores. Lower scores on inter-and intrapersonal understanding of social norms were both predicted by the presence of more autism-like traits while poorer interpersonal understanding of social norms performance was predicted by increasing age. These findings show that the ESCoT is a useful measure of social cognition and, unlike established tests of social cognition, performance is not predicted by measures of verbal comprehension and perceptual reasoning. This is particularly valuable to obtain an accurate assessment of the influence of age on our social cognitive abilities.</p></div

A Review of the Evidence Supporting the Taste of Non‐esterified Fatty Acids in Humans

Dietary fats contribute to the flavor of foods by multiple mechanisms. A role for their taste has only recently gained credence. Current evidence indicates non‐esterified fatty acids (NEFA) are the effective stimuli for the taste component. CD36 and GPR120 are putative receptors, but may not fully account for the totality of the range of sensations elicited by fatty acids. The sensory quality of long‐chain NEFA is not adequately characterized by commonly accepted taste primary qualities and has been termed oleogustus. There is marked individual variability in sensitivity to the taste of NEFA prompting hypotheses of genetic and environmental determinants. Though an association with BMI has been proposed, the preponderance of evidence is not supportive. The importance of oleogustus has not been fully established, but likely contributes to flavor, which influences food choice as well as lipid metabolism and chronic disease risk. A better understanding of oleogustus may provide insights useful for product formulation

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Measurement of the branching fraction for B−→D0K∗−B^- \to D^0 K^{*-}

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}

Observation of a significant excess of π0π0\pi^{0}\pi^{0} events in B meson decays

We present an observation of the decay $B^{0} \to \pi^{0} \pi^{0}$ based on a sample of 124 million $B\bar{B}$ pairs recorded by the BABAR detector at the PEP-II asymmetric-energy $B$ Factory at SLAC. We observe $46 \pm 13 \pm 3$ events, where the first error is statistical and the second is systematic, corresponding to a significance of 4.2 standard deviations including systematic uncertainties. We measure the branching fraction \BR(B^{0} \to \pi^{0} \pi^{0}) = (2.1 \pm 0.6 \pm 0.3) \times 10^{-6}, averaged over $B^{0}$ and $\bar{B}^{0}$ decays

Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

Peer reviewe

PIASγ Is Required for Faithful Chromosome Segregation in Human Cells

BACKGROUND: The precision of the metaphase-anaphase transition ensures stable genetic inheritance. The spindle checkpoint blocks anaphase onset until the last chromosome biorients at metaphase plate, then the bonds between sister chromatids are removed and disjoined chromatids segregate to the spindle poles. But, how sister separation is triggered is not fully understood. PRINCIPAL FINDINGS: We identify PIASγ as a human E3 sumo ligase required for timely and efficient sister chromatid separation. In cells lacking PIASγ, normal metaphase plates form, but the spindle checkpoint is activated, leading to a prolonged metaphase block. Sister chromatids remain cohered even if cohesin is removed by depletion of hSgo1, because DNA catenations persist at centromeres. PIASγ-depleted cells cannot properly localize Topoisomerase II at centromeres or in the cores of mitotic chromosomes, providing a functional link between PIASγ and Topoisomerase II. CONCLUSIONS: PIASγ directs Topoisomerase II to specific chromosome regions that require efficient removal of DNA catenations prior to anaphase. The lack of this activity activates the spindle checkpoint, protecting cells from non-disjunction. Because DNA catenations persist without PIASγ in the absence of cohesin, removal of catenations and cohesin rings must be regulated in parallel