Measurement of the electron transmission rate of the gating foil for the TPC of the ILC experiment

We have developed a gating foil for the time projection chamber envisaged as a central tracker for the international linear collider experiment. It has a structure similar to the Gas Electron Multiplier (GEM) with a higher optical aperture ratio and functions as an ion gate without gas amplification. The transmission rate for electrons was measured in a counting mode for a wide range of the voltages applied across the foil using an $^{55}$Fe source and a laser in the absence of a magnetic field. The blocking power of the foil against positive ions was estimated from the electron transmissions.Comment: 25 pages containing 14 figures and 1 tabl

Repeated mitral valve replacement in a patient with extensive annular calcification

<p>Abstract</p> <p>Background</p> <p>Mitral valve replacement in the presence of severe annular calcification is a technical challenge.</p> <p>Case report</p> <p>A 47-year-old lady who had undergone mitral and aortic valve replacement for rheumatic disease 27 years before presented with dyspnea. At reoperation, extensive mitral annular calcification was hindering the disc motion of the Starr-Edwards mitral prosthesis. The old prosthesis was removed and a St Jude Medical mechanical valve was implanted after thorough annular debridement. Postoperatively the patient developed paravalvular leak and hemolytic anemia, subsequently undergoing reoperation three days later. The mitral valve was replaced with an Edwards MIRA valve, with a bulkier sewing cuff, after more aggressive annular debridement. Although initially there was no paravalvular leak, it recurred five days later. The patient also developed a small cerebral hemorrhage. As the paravalvular leak and hemolytic anemia gradually worsened, the patient underwent reoperation 14 days later. A Carpentier-Edwards bioprosthetic valve with equine pericardial patches, one to cover the debrided calcified annulus, another as a collar around the prosthesis, was used to eliminate paravalvular leak. At 7 years postoperatively the patient is doing well without any evidence of paravalvular leak or structural valve deterioration.</p> <p>Conclusion</p> <p>Mitral valve replacement using a bioprosthesis with equine pericardial patches was useful to overcome recurrent paravalvular leak due to severe mitral annular calcification.</p

Towards the development of an EIT-based stretchable sensor for multi-touch industrial human-computer interaction systems

In human-computer interaction studies, an interaction is often considered as a kind of information or discrete internal states of an individual that can be transmitted in a loss-free manner from people to computing interfaces (or robotic interfaces) and vice-versa. This project aims to investigate processes capable of communicating and cooperating by adjusting their schedules to match the evolving execution circumstances, in a way that maximise the quality of their joint activities. By enabling human-computer interactions, the process will emerge as a framework based on the concept of expectancy, demand, and need of the human and computer together, for understanding the interplay between people and computers. The idea of this work is to utilise touch feedback from humans as a channel for communication thanks to an artificial sensitive skin made of a thin, flexible, and stretchable material acting as transducer. As a proof of concept, we demonstrate that the first prototype of our artificial sensitive skin can detect surface contacts and show their locations with an image reconstructing the internal electrical conductivity of the sensor

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation

Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product

Basal LAT-diacylglycerol-RasGRP1 Signals in T Cells Maintain TCRα Gene Expression

In contrast to the well-characterized T cell receptor (TCR) signaling pathways that induce genes that drive T cell development or polarization of naïve CD4 T cells into the diverse TH1, TH2, TH17 and Treg lineages, it is unclear what signals maintain specific gene expression in mature resting T cells. Resting T cells residing in peripheral lymphoid organs exhibit low-level constitutive signaling. Whereas tonic signals in B cells are known to be critical for survival, the roles of tonic signals in peripheral T cells are unknown. Here we demonstrate that constitutive signals in Jurkat T cell lines are transduced via the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain expression of TCRα mRNA and surface expression of the TCR/CD3 complex. Independent approaches of reducing basal activity through the LAT-diacylglycerol-RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased TCRα mRNA and surface TCR expression in Jurkat cells. However, loss of TCR expression takes several days in these cell line experiments. In agreement with these in vitro approaches, inducible deletion of Lat in vivo results in reduced TCRα mRNA- and surface TCR- expression in a delayed temporal manner as well. Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to silencing or repression of TCRα transcription. We postulate that basal LAT-diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T lymphocytes by maintaining proper gene expression programs

Listeria pathogenesis and molecular virulence determinants

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research