Performance of the ABCN-25 readout chip for the ATLAS Inner Detector Upgrade

We present the test results of the ABCN-25 front end chip implemented in CMOS 0.25 μm technology and optimised for the short, 2.5 cm, silicon strips intended to be used in the upgrade of the ATLAS Inner Detector. We have obtained the full functionality of the readout part, the expected performance of the analogue front-end and the operation of the power control circuits. The performance is evaluated in view of the minimization of the power consumption, as the upgrade detector may contain up to 70 million of channels. System tests with different power distribution schemes proposed for the future tracker detectors are possible with this chip. The ABCN-25 ASIC is now serving as the prototype readout chip in the developments of the modules and staves for the upgrade of the ATLAS Inner Detector

MicroRNA-155 is induced during the macrophage inflammatory response

The mammalian inflammatory response to infection involves the induction of several hundred genes, a process that must be carefully regulated to achieve pathogen clearance and prevent the consequences of unregulated expression, such as cancer. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators that has also been linked to cancer. However, the relationship between inflammation, innate immunity, and miRNA expression is just beginning to be explored. In the present study, we use microarray technology to identify miRNAs induced in primary murine macrophages after exposure to polyriboinosinic:polyribocytidylic acid or the cytokine IFN-{beta}. miR-155 was the only miRNA of those tested that was substantially up-regulated by both stimuli. It also was induced by several Toll-like receptor ligands through myeloid differentiation factor 88- or TRIF-dependent pathways, whereas up-regulation by IFNs was shown to involve TNF-{alpha} autocrine signaling. Pharmacological inhibition of the kinase JNK blocked induction of miR-155 in response to either polyriboinosinic:polyribocytidylic acid or TNF-{alpha}, suggesting that miR-155-inducing signals use the JNK pathway. Together, these findings characterize miR-155 as a common target of a broad range of inflammatory mediators. Importantly, because miR-155 is known to function as an oncogene, these observations identify a potential link between inflammation and cancer

Teenagers’ understandings of and attitudes towards vaccines and vaccine-preventable diseases: a qualitative study

<p>Background: To examine immunisation information needs of teenagers we explored understandings of vaccination and vaccine-preventable diseases, attitudes towards immunisation and experiences of immunisation. Diseases discussed included nine for which vaccines are currently offered in the UK (human papillomavirus, meningitis, tetanus, diphtheria, polio, whooping cough, measles, mumps and rubella), and two not currently included in the routine UK schedule (hepatitis B and chickenpox).</p> <p>Methods Twelve focus groups conducted between November 2010 and March 2011 with 59 teenagers (29 girls and 30 boys) living in various parts of Scotland.</p> <p>Results Teenagers exhibited limited knowledge and experience of the diseases, excluding chickenpox. Measles, mumps and rubella were perceived as severe forms of chickenpox-like illness, and rubella was not associated with foetal damage. Boys commonly believed that human papillomavirus only affects girls, and both genders exhibited confusion about its relationship with cancer. Participants considered two key factors when assessing the threat of diseases: their prevalence in the UK, and their potential to cause fatal or long-term harm. Meningitis was seen as a threat, but primarily to babies. Participants explained their limited knowledge as a result of mass immunisation making once-common diseases rare in the UK, and acknowledged immunisation's role in reducing disease prevalence.</p> <p>Conclusions While it is welcome that fewer teenagers have experienced vaccine-preventable diseases, this presents public health advocates with the challenge of communicating benefits of immunisation when advantages are less visible. The findings are timely in view of the Joint Committee on Vaccination and Immunisation's recommendation that a booster of meningitis C vaccine should be offered to teenagers; that teenagers did not perceive meningitis C as a significant threat should be a key concern of promotional information. While teenagers’ experiences of immunisation in school were not always positive, they seemed enthusiastic at the prospect of introducing more vaccines for their age group.</p&gt

Des ennemis héréditaires aux alliés, rapprochement franco-allemand après la Seconde Guerre mondiale

法德两国同属欧洲大陆的核心国家，更是当今世界格局中颇具影响力的大国。历史上，两国在不同时期都曾一度称雄欧洲，展现强国风范。当今法国人强烈的民族自豪感源自于他们骄傲的光荣历史。宣称“朕即天下”的路易十四曾大扩法国的疆域，使其成为17世纪欧洲最强大的国家。而拿破仑更是雄心勃勃地继续为法国开疆辟土，其帝国在鼎盛时期一度囊括了整个欧洲大陆。当时的法国比历史上任何国家都更接近于控制整个欧洲。德意志国家一向是推动欧洲历史发展的强大力量。神圣罗马帝国也曾经称霸西欧，而18世纪中后期的普鲁士也被视为欧洲强国。因此法德两国的一举一动都可能对欧洲的未来发展产生深刻影响。与此同时，作为邻国，两国因领土的接壤而被紧密...Comme les pays les plus importants sur le continent européen, la France et l’Allemagne sont tous les grandes puissances à l’échelle mondiale. Elles se disputaient l’hégémonie de l’Europe dans les différentes périodes de l’histoire européenne. La grande fierté nationale actuelle des Français dérive de l’histoire glorieuse de la France. A l’époque de Louis XIV, le territoire français e...学位：文学硕士院系专业：外文学院欧洲语言文学系_法语语言文学学号：1212006115035

Anthropology, Brokerage and Collaboration in the development of a Tongan Public Psychiatry: Local Lessons for Global Mental Health

The Global Mental Health (GMH) movement has revitalised questions of the translatability of psychiatric concepts and the challenges of community engagement in countries where knowledge of the biomedical basis for psychiatric diagnosis is limited or challenged by local cultural codes. In Tonga, the local psychiatrist Dr Puloka has successfully established a publicly accessible psychiatry that has raised admission rates for serious mental illness and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors and patients since 1998, this article offers an ethnographic contextualization of the development and reception of three key interventions during the 1990s inspired by traditional healing and reliant on the translation of psychiatric terms and diagnosis. Dr Puloka’s use of medical anthropological and transcultural psychiatry research informed a community engaged brokerage between the implications of psychiatric nosologies and local needs. As such it reveals deficiencies in current polarised positions on the GMH project and offers suggestions to address current challenges of the Global Mental Health movement

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

<p>Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.</p> <p>Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.</p> <p>Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.</p> <p>Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.</p&gt

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33

The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-house microarray data derived from purified hematopoietic stem cell populations. This effort led to the discovery of HSS1 (Hematopoietic Signal peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily conserved across species, phyla and even kingdoms, including mammals, invertebrates and plants. Structural analysis showed no homology between HSS1 and known proteins or known protein domains, indicating that it was a truly novel protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome 19q13.33, a genomic region implicated in various cancers, including malignant glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines greatly reduced their proliferation rates compared to mock-transfected cells. hHSS1 expression significantly affected the malignant phenotype of U87 cells both in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1 in high-grade gliomas was further supported by microarray data, which indicated that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal that HSS1 is a truly novel protein defining a new class of secreted factors, and that it may have an important role in cancer, particularly glioma