A TPC is considered as tracking detector at a future linear collider. The LCTPC (Linear Collider TPC) collaboration has therefore constructed a prototype TPC for R&D purposes. MPGD readout ...structures, such as Micromegas or GEMs, are being considered for the TPC since the demands on space and momentum resolution can not be met with a traditional wire based readout. The prototype TPC is placed in a 1 Tesla magnet at DESY and tested using an electron beam.
Analyses of data taken during two different measurement series, in 2009 and 2010, are presented here. The TPC was instrumented with a two layer GEM system and read out using modified electronics from the ALICE experiment, including the programmable charge sensitive preamp-shaper PCA16. The PCA16 chip has a number of programmable parameters which allows studies to determine the settings optimal to the final TPC. Here, the impact of the shaping time on the space resolution in the drift direction was studied. It was found that a shaping time of 60 ns is the best setting (of the available choices) for a sampling frequency of 20 MHz. In addition, the resolution in the bend plane was studied. Unfortunately, the measurements suffered from distortions in the electric field close to the readout, which deformed the track projections and had to be corrected for. This was done using the Millipede method. The final results obtained are a resolution of 59.1 ± 0.4 μm in the bend plane and 204 ± 9 μm in the drift direction, both extrapolated to zero drift distance. The measured values are consistent with the final goal of the ILD.
Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell ...is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human “KIR-ome” at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.
•Clonal-like expansion of NK cells in response to CMV infection causes stable imprints in the human KIR repertoire.•Education by inhibitory KIRs promotes the expansion of NK cells, causing repertoire skewing and a bias for self-specific inhibitory KIRs.
Background
Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25‐hydroxyvitamin D ...has not been reported.
Objective
To investigate the association between serum levels of 25‐hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men.
Methods
A population‐based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high‐resolution peripheral quantitative computed tomography, areal BMD by dual‐energy X‐ray absorptiometry and serum 25‐hydroxyvitamin D and parathyroid hormone levels by immunoassay.
Results
Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L−1) or insufficiency 25–49 nmol L−1, in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L−1), cortical porosity was 17.2% higher than in vitamin D‐sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25‐hydroxyvitamin D independently predicted cortical porosity (standardized β = −0.110, R2 = 1.1%, P = 0.024), area (β = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R2 = 0.9%, P = 0.04).
Conclusion
Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry.
Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a(+)DX5(-) NK cells with adaptive-like features. Development of this NK cell ...lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet(+)Eomes(-)CD49a(+) NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a(+) NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56(bright), and express low levels of CD16, CD57, and perforin. After stimulation, CD49a(+) NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a(+) NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.
Expression of inhibitory killer cell immunoglobulin-like receptors (KIRs) specific for self–major histocompatibility complex (MHC) class I molecules provides an educational signal that generates ...functional natural killer (NK) cells. However, the effects of activating KIRs specific for self-MHC class I on NK-cell education remain elusive. Here, we provide evidence that the activating receptor KIR2DS1 tunes down the responsiveness of freshly isolated human NK cells to target cell stimulation in donors homozygous for human leukocyte antigen (HLA)–C2, the ligand of KIR2DS1. The tuning was apparent in KIR2DS1+ NK cells lacking expression of inhibitory KIRs and CD94/NKG2A, as well as in KIR2DS1+ NK cells coexpressing the inhibitory MHC class I–specific receptors CD94/NKG2A and KIR2DL3, but not KIR2DL1. However, the tuning of responsiveness was restricted to target cell recognition because KIR2DS1+ NK cells responded well to stimulation with exogenous cytokines. Our results provide the first example of human NK-cell education by an activating KIR and suggest that the education of NK cells via activating KIRs is a mechanism to secure tolerance that complements education via inhibitory KIRs.
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