High Rate Proton Irradiation of 15mm Muon Drifttubes

Future LHC luminosity upgrades will significantly increase the amount of background hits from photons, neutrons and protons in the detectors of the ATLAS muon spectrometer. At the proposed LHC peak luminosity of 5*10^34 1/cm^2s, background hit rates of more than 10 kHz/cm^2 are expected in the innermost forward region, leading to a loss of performance of the current tracking chambers. Based on the ATLAS Monitored Drift Tube chambers, a new high rate capable drift tube detecor using tubes with a reduced diameter of 15mm was developed. To test the response to highly ionizing particles, a prototype chamber of 46 15mm drift tubes was irradiated with a 20 MeV proton beam at the tandem accelerator at the Maier-Leibnitz Laboratory, Munich. Three tubes in a planar layer were irradiated while all other tubes were used for reconstruction of cosmic muon tracks through irradiated and non-irradiated parts of the chamber. To determine the rate capability of the 15mm drift-tubes we investigated the effect of the proton hit rate on pulse height, efficiency and spatial resolution of the cosmic muon signals

MyHealthFrame - design and evaluation of a minimally invasive communication platform for telemedicine services aimed at older adults

MyHealthFrame is a communication platform that telemedicine (and well-being) services can leverage to deliver motivational messages and notifications to their end-users. Instead of being a telemedicine service in itself, MyHealthFrame is a channel through which external services can reach their users to provide reminders or deliver simple information such as number of steps. To its end-users, MyHealthFrame is a tablet device which is designed to be perceived as a photoframe and can be immersed in the users’ living environment. In this paper, we describe the design and the preliminary assessment of the platform. The results of the feasibility study with five older adults (65+) are promising

Performance of Drift-Tube Detectors at High Counting Rates for High-Luminosity LHC Upgrades

The performance of pressurized drift-tube detectors at very high background rates has been studied at the Gamma Irradiation Facility (GIF) at CERN and in an intense 20 MeV proton beam at the Munich Van-der-Graaf tandem accelerator for applications in large-area precision muon tracking at high-luminosity upgrades of the Large Hadron Collider (LHC). The ATLAS muon drifttube (MDT) chambers with 30 mm tube diameter have been designed to cope with and neutron background hit rates of up to 500 Hz/square cm. Background rates of up to 14 kHz/square cm are expected at LHC upgrades. The test results with standard MDT readout electronics show that the reduction of the drift-tube diameter to 15 mm, while leaving the operating parameters unchanged, vastly increases the rate capability well beyond the requirements. The development of new small-diameter muon drift-tube (sMDT) chambers for LHC upgrades is completed. Further improvements of tracking efficiency and spatial resolution at high counting rates will be achieved with upgraded readout electronics employing improved signal shaping for high counting rates

Circadian Programs of Transcriptional Activation, Signaling, and Protein Turnover Revealed by Microarray Analysis of Mammalian Cells

Many aspects of physiology and behavior are temporally organized into daily 24 hr rhythms, driven by an endogenous circadian clock. Studies in eukaryotes have identified a network of interacting genes forming interlocked autoregulatory feedback loops which underlie overt circadian organization in single cells [1, 2]. While in mammals the master oscillator resides in the suprachiasmatic nuclei of the hypothalamus [2], semiautonomous circadian oscillators also exist in peripheral tissues [3–5] and in immortalized fibroblasts, where rhythmicity is induced following a serum shock [6, 7]. We used this model system in combination with high-density cDNA microarrays to examine the magnitude and quality of clock control of gene expression in mammalian cells. Supported by application of novel bioinformatics tools, we find ∼2% of genes, including expected canonical clock genes, to show consistent rhythmic circadian expression across five independent experiments. Rhythmicity in most of these genes is novel, and they fall into diverse functional groups, highlighted by a predominance of transcription factors, ubiquitin-associated factors, proteasome components, and Ras/MAPK signaling pathway components. When grouped according to phase, 68% of the genes were found to peak during estimated subjective day, 32% during estimated subjective night, with a tendency to peak at a phase corresponding to anticipation of dawn or dusk

Converse Flexoelectricity of Low-Dimensional Bismuth Selenite (Bi2Se3) Revealed by Piezoresponse Force Microscopy (PFM)

Many kinds of two-dimensional (2D) van der Waals (vdW) have been demonstrated to exhibit electromechanical coupling effects, which makes them promising candidates for next-generation devices, such as piezotronics and nanogenerators. Recently, flexoelectricity was found to account for the out-of-plane electromechanical coupling in many 2D transition metal dichalcogenides (TMDs) who only exhibit in-plane piezoelectricity. However, low dimensional vdW three-dimensional (3D) topological insulators (TIs) have been overlooked regarding their electromechanical properties. In this study, for the first time, we experimentally investigate the electromechanical coupling of low dimensional 3D TIs with a centrosymmetric crystal structure, where a binary compound, bismuth selenite (Bi2Se3), is taken as an example. The results of piezoresponse force microscope (PFM) tests on the Bi2Se3 nanoflakes show that the material exhibits both out-of-plane and in-plane electromechanical responses. The Bi2Se3 nanoflake with a thickness of 37 nm possesses an effective out-of-plane piezoelectric coefficient of ~0.65 pm V-1. With careful analyses, the electromechanical responses are verified to arise from the converse flexoelectricity. The measured effective out-of-plane piezoelectric coefficient is mainly contributed by flexoelectric coefficient, {\mu}_39, which is estimated to be approximately 0.13 nC m-1. However, it is rather difficult to obtain the in-plane component of the flexoelectric tensor from the in-plane PFM measurements since the direction of the in-plane stress is always not normal to the AFM cantilever axis. The results provide useful guidance for understanding the flexoelectric effect of low dimensional vdW materials with centrosymmetric crystal structures. Moreover, the work can pave to way to explore the electromechanical devices based on the flexoelectricity of vdW TIs.Comment: 6 figure

Contribution of Symptomatic, Herbal Treatment Options to Antibiotic Stewardship and Microbiotic Health

Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens, depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host, in general (e.g., via the gut–brain axis), and their respective anatomical site, in particular (e.g., oral, urogenital, skin, or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives, such as non-steroidal anti-inflammatory drugs, may also influence the microbiota; thus, they can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections, without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy, with a generally favorable safety profile

Association of obesity with disease outcome in multiple sclerosis

BackgroundObesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation.MethodsThis nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were compared at baseline and at years 2, 4 and 6 between obese (body mass index, BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) patients and correlated with individual BMI values.ResultsPresence of obesity at disease onset was associated with higher disability at baseline and at 2, 4 and 6 years of follow-up (p<0.001). Median time to reach EDSS 3 was 0.99 years for patients with BMI ≥30 kg/m2 and 1.46 years for non-obese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI ≥30 kg/m2 compared with patients with BMI <30 kg/m2 after adjustment for sex, age, smoking (HR 1.87; 95% CI 1.3 to 2.6; log-rank test p<0.001) and independent of disease-modifying therapies. Obesity was not significantly associated with higher relapse rates, increased number of contrast-enhancing MRI lesions or higher MRI T2 lesion burden over 6 years of follow-up.ConclusionsObesity in newly diagnosed patients with MS is associated with higher disease severity and poorer outcome. Obesity management could improve clinical outcome of MS

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS

Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort

Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce.Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort.Design: Cross-sectional analysis within a multicenter observational study.Methods: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms.Results: Mean age was 34.3 years (95% confidence interval: 33.6-35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II > 8) were present in n = 256 (32.8%), 25-OH-VD deficiency (<20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient (c) = 1.48, p = 0.016], more severe fatigue (c = 0.26, p < 0.0001), lower 25-OH-VD (c = -0.03, p = 0.034) and smoking (c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not.Conclusion: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies

K(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K(2P)18.1 is a relevant regulator. Here, we identify K(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-kappa B-mediated K(2P)18.1 upregulation in tTreg progenitors. K(2P)18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-kappa B- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K(2P)18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K(2P)18.1 variant that is associated with poor clinical outcomes indicate that K(2P)18.1 also plays a role in human Treg development. Pharmacological modulation of K(2P)18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.Peer reviewe