Charge Berezinskii-Kosterlitz-Thouless transition in superconducting NbTiN films

A half-century after the discovery of the superconductor-insulator transition (SIT), one of the fundamental predictions of the theory, the charge Berezinskii-Kosterlitz-Thouless (BKT) transition that is expected to occur at the insulating side of the SIT, has remained unobserved. The charge BKT transition is a phenomenon dual to the vortex BKT transition, which is at the heart of the very existence of two-dimensional superconductivity as a zero-resistance state appearing at finite temperatures. The dual picture points to the possibility of the existence of a superinsulating state endowed with zero conductance at finite temperature. Here, we report the observation of the charge BKT transition on the insulating side of the SIT, identified by the critical behavior of the resistance. We find that the critical temperature of the charge BKT transition depends on the magnetic field exhibiting first the fast growth and then passing through the maximum at fields much less than the upper critical field. Finally, we ascertain the effects of the finite electrostatic screening length and its divergence at the magnetic field-tuned approach to the superconductor-insulator transition.Comment: 9 pages, 6 figure

A loess–paleosol record of climate and glacial history over the past two glacial–interglacial cycles (~150 ka), southern Jackson Hole, Wyoming

Loess accumulated on a Bull Lake outwash terrace of Marine Oxygen Isotope Stage 6 (MIS 6) age in southern Jackson Hole, Wyoming. The 9 m section displays eight intervals of loess deposition (Loess 1 to Loess 8, oldest), each followed by soil development. Our age-depth model is constrained by thermoluminescence, meteoric 10Be accumulation in soils, and cosmogenic 10Be surface exposure ages. We use particle size, geochemical, mineral-magnetic, and clay mineralogical data to interpret loess sources and pedogenesis. Deposition of MIS 6 loess was followed by a tripartite soil/thin loess complex (Soils 8, 7, and 6) apparently re!ecting the large climatic oscillations of MIS 5. Soil 8 (MIS 5e) shows the strongest development. Loess 5 accumulated during a glacial interval (~76–69 ka; MIS 4) followed by soil development under conditions wetter and probably colder than present. Deposition of thick Loess 3 (~43–51 ka, MIS 3) was followed by soil development comparable with that observed in Soil 1. Loess 1 (MIS 2) accumulated during the Pinedale glaciation and was followed by development of Soil 1 under a semiarid climate. This record of alternating loess deposition and soil development is compatible with the history of Yellowstone vegetation and the glacial !our record from the Sierra Nevada

`In pursuit of the Nazi mind?' the deployment of psychoanalysis in the allied struggle against Germany

This paper discusses how psychoanalytic ideas were brought to bear in the Allied struggle against the Third Reich and explores some of the claims that were made about this endeavour. It shows how a variety of studies of Fascist psychopathology, centred on the concept of superego, were mobilized in military intelligence, post-war planning and policy recommendations for ‘denazification’. Freud's ideas were sometimes championed by particular army doctors and government planners; at other times they were combined with, or displaced by, competing, psychiatric and psychological forms of treatment and diverse studies of the Fascist ‘personality’. This is illustrated through a discussion of the treatment and interpretation of the deputy leader of the Nazi Party, Rudolf Hess, after his arrival in Britain in 1941

The Role of the p53 Protein in the Selective Vulnerability of the Inner Retina to Transient Ischemia

PURPOSE. TO determine whether the p53 protein plays a role in the selective vulnerability of the inner retina to transient ischemia. METHODS. Transient retinal ischemia was induced using a high intraocular pressure (HIOP) model in the Sprague-Dawley rat for 60 minutes. Histopathologic outcome was determined 7 days after ischemia. In addition, analysis for evidence for apoptosis (TdT-dUTP terminal nick-end label [TUNEL] staining) and p53 protein expression (immunohistochemistry) was performed at several points during the reperfusion period. In a separate set of experiments, wild-type mice and two groups of transgenic mice, one homozygous and the other heterozygous for the p53 null gene, were also subjected to HIOP for 60 minutes, and histopathology was performed 7 days later. RESULTS. At 7 days subsequent to 60 minutes of ischemia in the rat, there was marked thinning of the inner retinal layers. There were scattered TUNEL-positive cells within the inner retina, peaking at 24 to 48 hours and persisting for at least 7 days. p53 immunochemistry demonstrated elevated protein levels within the inner retina; this finding peaked at 24 to 48 hours but was no longer present at 4 days after ischemia. TUNEL staining of the inner retina of the mouse was most prominent 24 hours subsequent to ischemia but persisted at 48 hours. Seven days subsequent to 60 minutes of ischemia in the wild-type and transgenic mice, histopathologic evaluation demonstrated preservation of the retinal histoarchitecture in the heterozygous group compared with the wildtype or homozygous animals

Structure-Based Discovery of Novel Ligands for the Orexin 2 Receptor

The orexin receptors are peptide-sensing G protein-coupled receptors that are intimately linked with regulation of the sleep/wake cycle. We used a recently solved X-ray structure of the orexin receptor subtype 2 in computational docking calculations with the aim to identify additional ligands with unprecedented chemotypes. We found validated ligands with a high hit rate of 29% out of those tested, none of them showing selectivity with respect to the orexin receptor subtype 1. Furthermore, of the higher-affinity compounds examined, none showed any agonist activity. While novel chemical structures can thus be found, selectivity is a challenge owing to the largely identical binding pockets

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

Objective: Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Materials and methods Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18–55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Results: Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of −1.6 (1.1) to −0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Conclusions: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1

The Wage and Non-wage Costs of Displacement: Evidence from Russia

This paper is the first to analyze the costs of job loss in Russia, using unique new data from the Russian Longitudinal Monitoring Survey over the years 2003-2008, including a special supplement on displacement that was initiated by us. We employ fixed effects regression models and propensity score matching techniques in order to establish the causal effect of displacement for displaced individuals. The paper is innovative insofar as we investigate fringe and in-kind benefits and the propensity to have an informal employment relationship as well as a permanent contract as relevant labor market outcomes upon displacement. We also analyze monthly earnings, hourly wages, employment and hours worked, which are traditionally investigated in the literature. Compared to the control group of non-displaced workers (i.e. stayers and quitters), displaced individuals face a significant income loss following displacement, which is mainly due to the reduction in employment and hours worked. This effect is robust to the definition of displacement. The losses seem to be more pronounced and are especially large for older workers with labor market experience and human capital acquired in Soviet times and for workers with primary and secondary education. Workers displaced from state firms experience particularly large relative losses in the short run, while such losses for workers laid off from private firms are more persistent. Turning to the additional non-conventional labor market outcomes, there is a loss in terms of the number of fringe and in-kind benefits for reemployed individuals but not in terms of their value. There is also some evidence of an increased probability of working in informal jobs if displaced. These results point towards the importance of both firm-specific human capital and of obsolete skills obtained under the centrally planned economy as well as to a wider occurrence of job insecurity among displaced workers

Ligand modulation of sidechain dynamics in a wild-type human GPCR

GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address this deficit, we generated samples of a wild-type GPCR (A2AR) that are deuterated apart from 1H/13C NMR probes at isoleucine d1 methyl groups, which facilitated 1H/13C methyl TROSY NMR measurements with opposing ligands. Our data indicate that low [Na+] is required to allow large agonist-induced structural changes in A2AR, and that patterns of sidechain dynamics substantially differ between agonist (NECA) and inverse agonist (ZM241385) bound receptors, with the inverse agonist suppressing fast ps-ns timescale motions at the G protein binding site. Our approach to GPCR NMR creates a framework for exploring how different regions of a receptor respond to different ligands or signaling proteins through modulation of fast ps-ns sidechain dynamics

A comparison of methods to adjust for continuous covariates in the analysis of randomised trials

BACKGROUND: Although covariate adjustment in the analysis of randomised trials can be beneficial, adjustment for continuous covariates is complicated by the fact that the association between covariate and outcome must be specified. Misspecification of this association can lead to reduced power, and potentially incorrect conclusions regarding treatment efficacy. METHODS: We compared several methods of adjustment to determine which is best when the association between covariate and outcome is unknown. We assessed (a) dichotomisation or categorisation; (b) assuming a linear association with outcome; (c) using fractional polynomials with one (FP1) or two (FP2) polynomial terms; and (d) using restricted cubic splines with 3 or 5 knots. We evaluated each method using simulation and through a re-analysis of trial datasets. RESULTS: Methods which kept covariates as continuous typically had higher power than methods which used categorisation. Dichotomisation, categorisation, and assuming a linear association all led to large reductions in power when the true association was non-linear. FP2 models and restricted cubic splines with 3 or 5 knots performed best overall. CONCLUSIONS: For the analysis of randomised trials we recommend (1) adjusting for continuous covariates even if their association with outcome is unknown; (2) keeping covariates as continuous; and (3) using fractional polynomials with two polynomial terms or restricted cubic splines with 3 to 5 knots when a linear association is in doubt