Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Social capital of venture capitalists and start-up funding

How does the social capital of venture capitalists (VCs) affect the funding of start-ups? By building on the rich social capital literature, we hypothesize a positive effect of VCs' social capital, derived from past syndication, on the amount of money that start-ups receive. Specifically, we argue that both structural and relational aspects of VCs' social networks provide VCs with superior access to information about current investment objects and opportunities to leverage them in the future, increasing their willingness to invest in these firms. Our empirical results, derived from a novel dataset containing more than 1,500 first funding rounds in the Internet and IT sector, strongly confirm our hypotheses. We discuss the implications of our findings for theories of venture capital and entrepreneurship, showing that the role and effect of VCs' social capital on start-up firms may be more complex than previously argued in the literature

Coulomb driven energy boost of heavy ions for laser plasma acceleration

An unprecedented increase of kinetic energy of laser accelerated heavy ions is demonstrated. Ultra thin gold foils have been irradiated by an ultra short laser pulse at an intensity of $6\times 10^{19}$ W/cm$^{2}$. Highly charged gold ions with kinetic energies up to $> 200$ MeV and a bandwidth limited energy distribution have been reached by using $1.3$ Joule laser energy on target. $1$D and $2$D Particle in Cell simulations show how a spatial dependence on the ions ionization leads to an enhancement of the accelerating electrical field. Our theoretical model considers a varying charge density along the target normal and is capable of explaining the energy boost of highly charged ions, leading to a higher efficiency in laser acceleration of heavy ions

The main concerns of European anaesthesiology postgraduate trainees: A European survey

This is the first study intended to identify the European anaesthesiology trainees' main concerns, to initiate a process of improvement of the training in anaesthesiology by the European Society of Anaesthesiology (ESA). The authors developed an electronic survey which addressed seven different concerns: autonomy transition, technical skills, exchange programs, residency costs, residency workload, employment prospects and educational contents/preparation for the European Diploma in Anaesthesiology and Intensive Care (EDAIC). The survey was disseminated by email to all anaesthesiology trainees registered in ESA and all European National Societies were asked to distribute the survey to their graduating trainees. 665 trainees initiated the survey with a completion rate of 54.6%. The trainees' main concerns were in descending order: educational contents, residency costs, employment prospects, residency workload, exchange programs, technical skills and autonomy transition. This report analyzes the three main concerns in more detail. 68% of respondents were unaware of the existence of the ESA e-learning platform. Other means to improve the preparation for the EDAIC such as a multiple-choice questions book should be developed. The main reason for not becoming an ESA Trainee member was the associated cost and 68% of respondents gave up activities or opportunities during their residency due to economic constraints; 56% of respondents considered emigrating for economic reasons and 28% elected Northern/Central Europe. The results of the present survey may provide additional background information for the development of specific improvements in strategies for training in anaesthesiology. (c) 2018 Elsevier Ltd. All rights reserved

Effects of Early Childhood Intervention on Fertility and Maternal Employment: Evidence from a Randomized Controlled Trial

This paper presents the results of a randomized study of a home visiting program implemented in Germany for low-income, first-time mothers. A major goal of the program is to improve the participants' economic self-sufficiency and family planning. I use administrative data from the German social security system and detailed telephone surveys to examine the effects of the intervention on maternal employment, welfare benefits, and household composition. The study reveals that the intervention unintentionally decreased maternal employment and increased subsequent births. These results contradict those of previous studies from the United States, where home visiting programs successfully increased employment and decreased fertility. Analyzing the reason for the different results, suggests that the program interacts with low employment incentives and generous welfare state arrangements for disadvantaged mothers with young children in Germany

Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses

Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4+CD44highCD62Llow). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4+T-cells were observed. Old CD4+ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4+CD25+FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4+ T-cell function and proliferation while CD4+CD25+FoxP3+ T-cells (Tregs) showed a well-preserved function

In situ nanoscopy of single-grain nanomorphology and ultrafast carrier dynamics in metal halide perovskites

Designing next-generation light-harvesting devices requires a detailed understanding of the transport of photoexcited charge carriers. The record-breaking efficiencies of metal halide perovskite solar cells have been linked to effective charge-carrier diffusion, yet the exact nature of charge-carrier out-of-plane transport remains notoriously difficult to explain. The characteristic spatial inhomogeneity of perovskite films with nanograins and crystallographic disorder calls for the simultaneous and hitherto elusive in situ resolution of the chemical composition, the structural phase and the ultrafast dynamics of the local out-of-plane transport. Here we simultaneously probe the intrinsic out-of-plane charge-carrier diffusion and the nanoscale morphology by pushing depth-sensitive terahertz near-field nanospectroscopy to extreme subcycle timescales. In films of the organic–inorganic metal halide perovskite FA0.83Cs0.17Pb(I1−xClx)3 (where FA is formamidinium), domains of the cubic α-phase are clearly distinguished from the trigonal δ-phase and PbI2 nano-islands. By analysing deep-subcycle time shifts of the scattered terahertz waveform after photoexcitation, we access the vertical charge-carrier dynamics within single grains. At all of the measured locations, despite topographic irregularities, diffusion is surprisingly homogeneous on the 100 nm scale, although it varies between mesoscopic regions. Linking in situ carrier transport with nanoscale morphology and chemical composition could introduce a paradigm shift for the analysis and optimization of next-generation optoelectronics that are based on nanocrystalline materials