Critical sets of nonlinear Sturm-Liouville operators of Ambrosetti-Prodi type

The critical set C of the operator F:H^2_D([0,pi]) -> L^2([0,pi]) defined by F(u)=-u''+f(u) is studied. Here X:=H^2_D([0,pi]) stands for the set of functions that satisfy the Dirichlet boundary conditions and whose derivatives are in L^2([0,pi]). For generic nonlinearities f, C=\cup C_k decomposes into manifolds of codimension 1 in X. If f''0, the set C_j is shown to be non-empty if, and only if, -j^2 (the j-th eigenvalue of u -> u'') is in the range of f'. The critical components C_k are (topological) hyperplanes.Comment: 6 pages, no figure

Understanding the Basis for Down Syndrome Phenotypes

Down syndrome is a collection of features that are caused by trisomy for human Chromosome 21. While elevated transcript levels of the more than 350 genes on the chromosome are primarily responsible, it is likely that multiple genetic mechanisms underlie the numerous ways in which development and function diverge in individuals with trisomy 21 compared to euploid individuals. We consider genotype–phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy

Different MAPT haplotypes influence expression of total MAPT in postmortem brain tissue

The MAPT gene, encoding the microtubule-associated protein tau on chromosome 17q21.31, is result of an inversion polymorphism, leading to two allelic variants (H1 and H2). Homozygosity for the more common haplotype H1 is associated with an increased risk for several tauopathies, but also for the synucleinopathy Parkinson's disease (PD). In the present study, we aimed to clarify whether the MAPT haplotype influences expression of MAPT and SNCA, encoding the protein alpha-synuclein (alpha-syn), on mRNA and protein levels in postmortem brains of PD patients and controls. We also investigated mRNA expression of several other MAPT haplotype-encoded genes. Postmortem tissues from cortex of fusiform gyrus (ctx-fg) and of the cerebellar hemisphere (ctx-cbl) of neuropathologically confirmed PD patients (n = 95) and age- and sex-matched controls (n = 81) were MAPT haplotype genotyped to identify cases homozygous for either H1 or H2. Relative expression of genes was quantified using real-time qPCR;soluble and insoluble protein levels of tau and alpha-syn were determined by Western blotting. Homozygosity for H1 versus H2 was associated with increased total MAPT mRNA expression in ctx-fg regardless of disease state. Inversely, H2 homozygosity was associated with markedly increased expression of the corresponding antisense MAPT-AS1 in ctx-cbl. PD patients had higher levels of insoluble 0N3R and 1N4R tau isoforms regardless of the MAPT genotype. The increased presence of insoluble alpha-syn in PD patients in ctx-fg validated the selected postmortem brain tissue. Our findings in this small, but well controlled cohort of PD and controls support a putative biological relevance of tau in PD. However, we did not identify any link between the disease-predisposing H1/H1 associated overexpression of MAPT with PD status. Further studies are required to gain a deeper understanding of the potential regulatory role of MAPT-AS1 and its association to the disease-protective H2/H2 condition in the context of PD

Lattice dynamics and correlated atomic motion from the atomic pair distribution function

The mean-square relative displacements (MSRD) of atomic pair motions in crystals are studied as a function of pair distance and temperature using the atomic pair distribution function (PDF). The effects of the lattice vibrations on the PDF peak widths are modelled using both a multi-parameter Born von-Karman (BvK) force model and a single-parameter Debye model. These results are compared to experimentally determined PDFs. We find that the near-neighbor atomic motions are strongly correlated, and that the extent of this correlation depends both on the interatomic interactions and crystal structure. These results suggest that proper account of the lattice vibrational effects on the PDF peak width is important in extracting information on static disorder in a disordered system such as an alloy. Good agreement is obtained between the BvK model calculations of PDF peak widths and the experimentally determined peak widths. The Debye model successfully explains the average, though not detailed, natures of the MSRD of atomic pair motion with just one parameter. Also the temperature dependence of the Debye model largely agrees with the BvK model predictions. Therefore, the Debye model provides a simple description of the effects of lattice vibrations on the PDF peak widths.Comment: 9 pages, 11 figure

Effect of quantum confinement on exciton-phonon interactions

We investigate the homogeneous linewidth of localized type-I excitons in type-II GaAs/AlAs superlattices. These localizing centers represent the intermediate case between quasi-two-dimensional (Q2D) and quasi-zero-dimensional localizations. The temperature dependence of the homogeneous linewidth is obtained with high precision from micro-photoluminescence spectra. We confirm the reduced interaction of the excitons with their environment with decreasing dimensionality except for the coupling to LO-phonons. The low-temperature limit for the linewidth of these localized excitons is five times smaller than that of Q2D excitons. The coefficient of exciton-acoustic-phonon interaction is 5 ~ 6 times smaller than that of Q2D excitons. An enhancement of the average exciton-LO-phonon interaction by localization is found in our sample. But this interaction is very sensitive to the detailed structure of the localizing centers.Comment: 6 pages, 4 figure

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Performance of the LHCb muon system with cosmic rays

The LHCb Muon system performance is presented using cosmic ray events collected in 2009. These events allowed to test and optimize the detector configuration before the LHC start. The space and time alignment and the measurement of chamber efficiency, time resolution and cluster size are described in detail. The results are in agreement with the expected detector performance.Comment: Submitted to JINST and accepte

Childhood adversity, mental ill-health and aggressive behavior in an African orphanage: Changes in response to trauma-focused therapy and the implementation of a new instructional system

<p>Abstract</p> <p>Background</p> <p>The number of orphans in Sub-Saharan Africa is constantly rising. While it is known that family or community care is preferable over institutional care of African orphans, little is known about the quality of care in orphanages and possibilities of improvement.</p> <p>Study 1</p> <p>Methods</p> <p>Exposure to traumatic stress, experiences of violence in the home, school and orphanage, as well as mental ill-health and aggression of 38 children (mean age of <it>M </it>= 8.64 years) living in an orphanage in rural Tanzania were assessed at two time points. The severity of post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and internalizing and externalizing problems were used as indicators of mental ill-health.</p> <p>Results</p> <p>Violence experienced in the orphanage correlated more strongly with all indicators of mental ill-health than violence in the former home, school or neighborhood at time point 1. Additionally, violence experienced in the orphanage had a positive relationship with the aggressive behavior of the children at time point 2.</p> <p>Study 2</p> <p>Methods</p> <p>With the help of the pre-post assessment of Study 1, the implementation of a new instructional system and psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.</p> <p>Results</p> <p>In response to both, a change in the instructional system and psychotherapeutic treatment of PTSD, a massive decline in experienced violence and in the severity of PTSD-symptoms was found, whereas depressive symptoms and internalizing and externalizing problems exhibited little change.</p> <p>Conclusions</p> <p>These studies show that violence, especially in the orphanage, can severely contribute to mental ill-health in orphans and that mental health can be improved by implementing a new instructional system and psychotherapeutic treatment in an orphanage. Moreover, the results indicate that the experience of violence in an orphanage also plays a crucial role in aggressive behavior of the orphans.</p

Measurement of the CKM angle γ from a combination of B±→Dh± analyses

A combination of three LHCb measurements of the CKM angle γ is presented. The decays B±→D K± and B±→Dπ± are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+K−, π+π−, K±π∓, K±π∓π±π∓, K0Sπ+π−, or K0S K+K− final states. All measurements use a dataset corresponding to 1.0 fb−1 of integrated luminosity. Combining results from B±→D K± decays alone a best-fit value of γ =72.0◦ is found, and confidence intervals are set γ ∈ [56.4,86.7]◦ at 68% CL, γ ∈ [42.6,99.6]◦ at 95% CL. The best-fit value of γ found from a combination of results from B±→Dπ± decays alone, is γ =18.9◦, and the confidence intervals γ ∈ [7.4,99.2]◦ ∪ [167.9,176.4]◦ at 68% CL are set, without constraint at 95% CL. The combination of results from B± → D K± and B± → Dπ± decays gives a best-fit value of γ =72.6◦ and the confidence intervals γ ∈ [55.4,82.3]◦ at 68% CL, γ ∈ [40.2,92.7]◦ at 95% CL are set. All values are expressed modulo 180◦, and are obtained taking into account the effect of D0–D0 mixing