Divergence at low bias and down-mixing of the current noise in a diffusive superconductor-normal metal-superconductor junction

We present current noise measurements in a long diffusive superconductor-normal-metal-superconductor junction in the low voltage regime, in which transport can be partially described in terms of coherent multiple Andreev reflections. We show that, when decreasing voltage, the current noise exhibits a strong divergence together with a broad peak. We ascribe this peak to the mixing between the ac- Josephson current and the noise of the junction itself. We show that the junction noise corresponds to the thermal noise of a nonlinear resistor 4kBT=R with R V = I V and no adjustable parameters

The Effect of Urban Street Gang Densities on Small Area Homicide Incidence in a Large Metropolitan County, 1994–2002

The presence of street gangs has been hypothesized as influencing overall levels of violence in urban communities through a process of gun–drug diffusion and cross-type homicide. This effect is said to act independently of other known correlates of violence, i.e., neighborhood poverty. To test this hypothesis, we independently assessed the impact of population exposure to local street gang densities on 8-year homicide rates in small areas of Los Angeles County, California. Homicide data from the Los Angeles County Coroners Office were analyzed with original field survey data on street gang locations, while controlling for the established covariates of community homicide rates. Bivariate and multivariate regression analyses explicated strong relationships between homicide rates, gang density, race/ethnicity, and socioeconomic structure. Street gang densities alone had cumulative effects on small area homicide rates. Local gang densities, along with high school dropout rates, high unemployment rates, racial and ethnic concentration, and higher population densities, together explained 90% of the variation in local 8-year homicide rates. Several other commonly considered covariates were insignificant in the model. Urban environments with higher densities of street gangs exhibited higher overall homicide rates, independent of other community covariates of homicide. The unique nature of street gang killings and their greater potential to influence future local rates of violence suggests that more direct public health interventions are needed alongside traditional criminal justice mechanisms to combat urban violence and homicides

Situational prevention and public transport crime in El Salvador

By any standard, there is a serious problem of crime on the public transport system in El Salvador. Guided by crime opportunity theory, this study undertook a rapid assessment of the problem consisting of a systematic observation of public transport in El Salvador and focus group discussions with passengers, bus operators, police and bus company owners/managers. The purposes were (1) to describe the main forms of crime and disorder afflicting the system, (2) to identify features of the system that contribute to the high levels of crime and disorder, and (3) to identify preventive measures, consistent with international experience. A program of situational crime prevention measures was identified which consisted of two main kinds: (1) measures relating to the operations of the bus system as a whole, intended to help to create a more orderly and secure transport environment and, (2) more specific measures designed to reduce opportunities for crimes occurring on buses or at bus stops, such as homicides, robberies, and sexual assaults on women. Future research and implementation of the preventive measures are discussed

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Barriers and facilitators to implementing community outreach work, and inter-professional collaboration with regional partners

Abstract : Objective. Community outreach workers support individuals in accessing the health and community services they require through various forms of proximity approaches. Even though community outreach has been available in the province of Quebec (Canada) for the past 40 years, it is still difficult to implement and sustain, especially with families of young children. The aim of this study was to document barriers and facilitators to implementing community outreach practices, and to describe how such workers collaborate with sectoral (e.g. health care) and inter-sectoral (e.g. municipalities, community organizations, schools) partners. Methodology. We performed a content analysis on 55 scientific and grey literature documents, and transcriptions of 24 individual interviews and 3 focus groups with stakeholders including parents, community outreach workers, health care employees, and inter-sectoral partners. Results. This study reveals four categories of barriers and facilitators to the implementation of community outreach work (i.e. organizational factors, nature of the work and worker-related factors, family-related factors, external factors). With regards to collaboration, community outreach workers deal with various partners. Good inter-professional collaboration is achieved through positive interactions and communication, shared or co-developed activities for the families, co-intervention with families, and strategies to enhance role awareness and inter-sectoral meetings. Conclusion. Results highlighted that many factors interact and can either influence, positively or negatively, the opportunity to implement community outreach work. The collaborative practices identified may help to maximize facilitators and overcome barriers. Advocacy and a better understanding of how to integrate community outreach work within health services while maintaining the workers’ flexibility are needed to sustain this practice

Validity of mobile electronic data capture in clinical studies: a pilot study in a pediatric population.

BACKGROUND: Clinical studies in children are necessary yet conducting multiple visits at study centers remains challenging. The success of "care-at-home" initiatives and remote clinical trials suggests their potential to facilitate conduct of pediatric studies. This pilot aimed to study the feasibility of remotely collecting valid (i.e. complete and correct) saliva samples and clinical data utilizing mobile technology. METHODS: Single-center, prospective pilot study in children undergoing elective tonsillectomy at the University of Basel Children's Hospital. Data on pain scores and concomitant medication and saliva samples were collected by caregivers on two to four inpatient study days and on three consecutive study days at home. A tailored mobile application developed for this study supported data collection. The primary endpoint was the proportion of complete and correct caregiver-collected data (pain scale) and saliva samples in the at-home setting. Secondary endpoints included the proportion of complete and correct saliva samples in the inpatient setting, subjective feasibility for caregivers, and study cost. RESULTS: A total number of 23 children were included in the study of which 17 children, median age 6.0 years (IQR 5.0, 7.4), completed the study. During the at-home phase, 71.9% [CI = 64.4, 78.6] of all caregiver-collected pain assessments and 53.9% [CI = 44.2, 63.4] of all saliva samples were complete and correct. Overall, 64.7% [CI = 58.7, 70.4] of all data collected by caregivers at home was complete and correct. The predominant reason for incorrectness of data was adherence to the timing of predefined patient actions. Participating caregivers reported high levels of satisfaction and willingness to participate in similar trials in the future. Study costs for a potential sample size of 100 patients were calculated to be 20% lower for the at-home than for a traditional in-patient study setting. CONCLUSIONS: Mobile device supported studies conducted at home may provide a cost-effective approach to facilitate conduct of clinical studies in children. Given findings in this pilot study, data collection at home may focus on electronic data capture rather than biological sampling

A Fluorescence Reporter Model Defines “Tip-DCs” as the Cellular Source of Interferon β in Murine Listeriosis

Production of type I interferons, consisting mainly of multiple IFNα subtypes and IFNβ, represents an essential part of the innate immune defense against invading pathogens. While in most situations, namely viral infections, this class of cytokines is indispensable for host survival they mediate a detrimental effect during infection with L. monocytogenes by rendering macrophages insensitive towards IFNγ signalling which leads to a lethal bacterial pathology in mice. Due to a lack of suitable analytic tools the precise identity of the cell population responsible for type I IFN production remains ill-defined and so far these cells have been described to be macrophages. As in general IFNβ is the first type I interferon to be produced, we took advantage of an IFNβ fluorescence reporter-knockin mouse model in which YFP is expressed from a bicistronic mRNA linked by an IRES to the endogenous ifnb mRNA to assess the IFNβ production on a single cell level in situ. Our results showed highest frequencies and absolute numbers of IFNβ+ cells in the spleen 24 h after infection with L. monocytogenes where they were located predominately in the white pulp within the foci of infection. Detailed FACS surface marker analyses, intracellular cytokine stainings and T cell proliferation assays revealed that the IFNβ+ cells were a phenotypically and functionally further specialized subpopulation of TNF and iNOS producing DCs (Tip-DCs) which are known to be essential for the early containment of L. monocytogenes infection. We proved that the IFNβ+ cells exhibited the hallmark characteristics of Tip-DCs as they produced iNOS and TNF and possessed T cell priming abilities. These results point to a yet unappreciated ambiguous role for a multi-effector, IFNβ producing subpopulation of Tip-DCs in controlling the balance between containment of L. monocytogenes infection and effects detrimental to the host driven by IFNβ

Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection

Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection

TLR9 agonists induced cell death in Burkitt's lymphoma cells is variable and influenced by TLR9 polymorphism

Toll-like receptor 9 (TLR9) triggering is a promising novel strategy to combat cancer as it induces innate and adaptive immunity responses. B-cell lymphoma is unique in this context as tumor cells express TLR9 and may harbor latent Epstein-Barr virus (EBV), a gamma-herpesvirus with remarkable oncogenic potential when latent. Latent EBV may be promoted by TLR9 triggering via suppression of lytic EBV. Here, we elaborated an initial assessment of the impact of TLR9 triggering on EBV-positive and EBV-negative B-cell lymphoma using Burkitt's lymphoma (BL) cell lines as an in vitro model. We show that, independent of the presence of EBV, the TLR9 ligand oligodeoxynucleotide (ODN) CpG-2006 may or may not induce caspase-dependent cell death in BL cells. Moreover, ODN CpG-2006-induced cell death responses of BL cells were associated with TLR9 single-nucleotide polymorphisms (SNPs) rs5743836 or rs352140, which we detected in primary BL tumors and in peripheral blood from healthy individuals at similar frequencies. Thus, our findings suggest that the effect of TLR9 agonists on BL cells should be tested in vitro before installment of therapy and TLR9 SNPs in BL patients should be determined as potential biological markers for the therapeutic response to treatment targeting innate immunity