Josephson surface plasmons in spatially confined cuprate superconductors

In this work, we generalize the theory of localized surface plasmons to the case of high-Tc cuprate superconductors, spatially confined in the form of small spherical particles. At variance from ordinary metals, cuprate superconductors are characterized by a low-energy bulk excitation known as the Josephson plasma wave (JPW), arising from interlayer tunneling of the condensate along the c-axis. The effect of the JPW is revealed in a characteristic spectrum of surface excitations, which we call Josephson surface plasmons. Our results, which apply to any material with a strongly anisotropic electromagnetic response, are worked out in detail for the case of multilayered superconductors supporting both low-frequency (acoustic) and transverse-optical JPW. Spatial confinement of the Josephson plasma waves may represent a new degree of freedom to engineer their frequencies and to explore the link between interlayer tunnelling and high-Tc superconductivity

Optimization of a 96-Well Electroporation Assay for Postnatal Rat CNS Neurons Suitable for Cost–Effective Medium-Throughput Screening of Genes that Promote Neurite Outgrowth

Following an injury, central nervous system (CNS) neurons show a very limited regenerative response which results in their failure to successfully form functional connections with their original target. This is due in part to the reduced intrinsic growth state of CNS neurons, which is characterized by their failure to express key regeneration-associated genes (RAGs) and by the presence of growth inhibitory molecules in CNS environment that form a molecular and physical barrier to regeneration. Here we have optimized a 96-well electroporation and neurite outgrowth assay for postnatal rat cerebellar granule neurons (CGNs) cultured upon an inhibitory cellular substrate expressing myelin-associated glycoprotein or a mixture of growth inhibitory chondroitin sulfate proteoglycans. Optimal electroporation parameters resulted in 28% transfection efficiency and 51% viability for postnatal rat CGNs. The neurite outgrowth of transduced neurons was quantitatively measured using a semi-automated image capture and analysis system. The neurite outgrowth was significantly reduced by the inhibitory substrates which we demonstrated could be partially reversed using a Rho Kinase inhibitor. We are now using this assay to screen large sets of RAGs for their ability to increase neurite outgrowth on a variety of growth inhibitory and permissive substrates

categoryCompare, an analytical tool based on feature annotations

Assessment of high-throughput—omics data initially focuses on relative or raw levels of a particular feature, such as an expression value for a transcript, protein, or metabolite. At a second level, analyses of annotations including known or predicted functions and associations of each individual feature, attempt to distill biological context. Most currently available comparative- and meta-analyses methods are dependent on the availability of identical features across data sets, and concentrate on determining features that are differentially expressed across experiments, some of which may be considered “biomarkers.” The heterogeneity of measurement platforms and inherent variability of biological systems confounds the search for robust biomarkers indicative of a particular condition. In many instances, however, multiple data sets show involvement of common biological processes or signaling pathways, even though individual features are not commonly measured or differentially expressed between them. We developed a methodology, categoryCompare, for cross-platform and cross-sample comparison of high-throughput data at the annotation level. We assessed the utility of the approach using hypothetical data, as well as determining similarities and differences in the set of processes in two instances: (1) denervated skin vs. denervated muscle, and (2) colon from Crohn's disease vs. colon from ulcerative colitis (UC). The hypothetical data showed that in many cases comparing annotations gave superior results to comparing only at the gene level. Improved analytical results depended as well on the number of genes included in the annotation term, the amount of noise in relation to the number of genes expressing in unenriched annotation categories, and the specific method in which samples are combined. In the skin vs. muscle denervation comparison, the tissues demonstrated markedly different responses. The Crohn's vs. UC comparison showed gross similarities in inflammatory response in the two diseases, with particular processes specific to each disease

Large-scale tests of a low-rise unreinforced masonry building system

Issued as final repor

Phase 2 study of RO4929097, a gamma‐secretase inhibitor, in metastatic melanoma: SWOG 0933

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110565/1/cncr29055.pd

How Well Does Societal Mobility Restriction Help Control the COVID-19 Pandemic? Evidence from Real-Time Evaluation

One of the most widely implemented policy response to the novel coronavirus (SARS-CoV-2) pandemic has been the imposition of restrictions on mobility (1). These restrictions have included both incentives, encouraging working from home, supported by a wide range of online activities such as meetings, lessons, and shopping, and sanctions, such as stay at home orders, restrictions on travel, and closure of shops, offices, and public transport (2-5). The measures constitute a major component of efforts to control the COVID-19 pandemic. Compared to previous epidemic responses, they are unprecedented in both scale and scope (6). The rationale underpinning these public health measures is that restricting normal activities decreases the number, duration, and proximity of interpersonal contacts and thus the potential for viral transmission. Transmission simulations using complex mathematical modelling have built on past experience such as the 1918 influenza epidemic (7), as well as assumptions about the contemporary scale and nature of contact in populations (8). However, the initial models were not always founded on empirical evidence from behavioral scientists on the feasibility or sustainability of mass social and behavior change in contemporary society. While reductions in interpersonal contact and increases in physical distancing are known to decrease respiratory infection spread (9), the paucity of recent examples of large-scale restrictions on mobility has limited the scope for research on their impact on transmission. Where restrictions have been imposed, as with Ebola, they have involved diseases with a different mode of transmission. Nonetheless, the rapidity of progression of this pandemic has forced many governments into trialing various approaches to containment with limited evidence of effectiveness (10). More conventional public health prevention measures (such as quarantine of contacts, isolation of infected individuals and contact tracing) and control measures in health systems (such as patient flow segregation, negative pressure ventilation, and use of personal protective equipment) (11-14), have been applied widely to control the epidemic in many countries as part of a portfolio of policy responses. However, mobility restriction as a new large-scale mass behavioral and social prescription has incurred considerable costs (15, 16). Estimates suggest global GDP growth has fallen by as much as 10% (17), at least in part due to mobility restriction policies. Although views differ, not least because of the lack of information of what would happen if the disease was unchecked and the emerging evidence of persisting disability in survivors, some have argued that this is greater than would be accounted for by the economic impact of direct illness and deaths from COVID-19 (18, 19). To inform decisions on large scale restrictions of mobility, there is an urgent need to assess their effectiveness in limiting pandemic spread. To this end, we examined the association of mobility with COVID-19 incidence in Organization of Economic Cooperation and Development (OECD) countries and equivalent economies such as Singapore and Taiwan

Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D

Medulloblastoma is the most common malignant brain tumor of childhood. Despite numerous advances, clinical challenges range from recurrent and progressive disease to long-term toxicities in survivors. The lack of more effective, less toxic therapies results from our limited understanding of medulloblastoma growth. Although TP53 is the most commonly altered gene in cancers, it is rarely mutated in medulloblastoma. Accumulating evidence, however, indicates that TP53 pathways are disrupted in medulloblastoma. Wild-typep53-induced phosphatase 1 (WIP1 or PPM1D) encodes a negative regulator of p53. WIP1 amplification (17q22-q23) and its overexpression have been reported in diverse cancer types. We examined primary medulloblastoma specimens and cell lines, and detected WIP1 copy gain and amplification prevalent among but not exclusively in the tumors with 17q gain and isochromosome 17q (i17q), which are among the most common cytogenetic lesions in medulloblastoma. WIP1 RNA levels were significantly higher in the tumors with 17q gain or i17q. Immunoblots confirmed significant WIP1 protein in primary tumors, generally higher in those with 17q gain or i17q. Under basal growth conditions and in response to the chemotherapeutic agent, etoposide, WIP1 antagonized p53-mediated apoptosis in medulloblastoma cell lines. These results indicate that medulloblastoma express significant levels of WIP1 that modulate genotoxic responsiveness by negatively regulating p53

Taking It to the Extreme:The Effect of Coalition Cabinets on Foreign Policy

Institutional constraints have been offered by some scholars as an explanation for why multiparty coalitions should be more peaceful than single-party cabinets. Yet others see the same institutional setting as a prescription for more aggressive behavior. Recent research has investigated these conflicting expectations, but with mixed results. We examine the theoretical bases for these alternative expectations about the effects of coalition politics on foreign policy. We find that previous research is limited theoretically by confounding institutional effects with policy positions, and empirically by analyzing only international conflict data. We address these limitations by examining cases of foreign policy behavior using the World Event/Interaction Survey (WEIS) dataset. Consistent with our observation that institutional constraints have been confounded with policy positions, we find that coalitions are neither more aggressive nor more peaceful, but do engage in more extreme foreign policy behaviors. These findings are discussed with regard to various perspectives on the role of institutions in shaping foreign policy behavior.</p