Atmospheric bending effects in GNSS tomography

In Global Navigation Satellite System (GNSS) tomography, precise information about the tropospheric water vapor distribution is derived from integral measurements like ground-based GNSS slant wet delays (SWDs). Therefore, the functional relation between observations and unknowns, i.e., the signal paths through the atmosphere, have to be accurately known for each station–satellite pair involved. For GNSS signals observed above a 15∘ elevation angle, the signal path is well approximated by a straight line. However, since electromagnetic waves are prone to atmospheric bending effects, this assumption is not sufficient anymore for lower elevation angles. Thus, in the following, a mixed 2-D piecewise linear ray-tracing approach is introduced and possible error sources in the reconstruction of the bended signal paths are analyzed in more detail. Especially if low elevation observations are considered, unmodeled bending effects can introduce a systematic error of up to 10–20&thinsp;ppm, on average 1–2&thinsp;ppm, into the tomography solution. Thereby, not only the ray-tracing method but also the quality of the a priori field can have a significant impact on the reconstructed signal paths, if not reduced by iterative processing. In order to keep the processing time within acceptable limits, a bending model is applied for the upper part of the neutral atmosphere. It helps to reduce the number of processing steps by up to 85&thinsp;% without significant degradation in accuracy. Therefore, the developed mixed ray-tracing approach allows not only for the correct treatment of low elevation observations but is also fast and applicable for near-real-time applications.</p

Simple Systematic Synthesis of Periodic Mesoporous Organosilica Nanoparticles with Adjustable Aspect Ratios

One-dimensional periodic mesoporous organosilica (PMO) nanoparticles with tunable aspect ratios are obtained from a chain-type molecular precursor octaethoxy-1,3,5-trisilapentane. The aspect ratio can be tuned from 2:1 to >20:1 simply by variation in the precursor concentration in acidic aqueous solutions containing constant amounts of triblock copolymer Pluronic P123. The mesochannels are highly ordered and are oriented parallel to the longitudinal axis of the PMO particles. No significant Si–C bond cleavage occurs during the synthesis according to29Si MAS NMR. The materials exhibit surface areas between 181 and 936 m2 g−1

Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans

Infection by human cytomegalovirus (HCMV) leads to NKG2C-driven expansion of adaptive natural killer (NK) cells, contributing to host defense. However, approximately 4% of all humans carry a homozygous deletion of the gene that encodes NKG2C ($\textit{NKG2C}^{-/-}$). Assessment of NK cell repertoires in 60 $\textit{NKG2C}^{-/-}$ donors revealed a broad range of NK cell populations displaying characteristic footprints of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon (IFN)-$\gamma$ promoter. We found that both NKG2C$^{-}$ and NKG2C$^{+}$ adaptive NK cells expressed high levels of CD2, which synergistically enhanced ERK and S6RP phosphorylation following CD16 ligation. Notably, CD2 co-stimulation was critical for the ability of adaptive NK cells to respond to antibody-coated target cells. These results reveal an unexpected redundancy in the human NK cell response to HCMV and suggest that CD2 provides "signal 2" in antibody-driven adaptive NK cell responses.This work was supported by grants from the Swedish Research Council, the Swedish Children’s Cancer Society, the Swedish Cancer Society, the Tobias Foundation, the Swedish Foundation for Strategic Research, the Karolinska Institutet, the Wenner-Gren Foundation, the Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, and the KG Jebsen Center for Cancer Immunotherapy. J.T. and J.A.T. are supported by the MRC and the Welcome Trust with partial funding from the National Institute for Health Research Cambridge Biomedical Research Centre. V.B. is supported by the French National Research Agency (ANR) (grant no. NKIR-ANR-13-PDOC- 0025-01)

The importance of nerve microenvironment for schwannoma development

Schwannomas are predominantly benign nerve sheath neoplasms caused by Nf2 gene inactivation. Presently, treatment options are mainly limited to surgical tumor resection due to the lack of effective pharmacological drugs. Although the mechanistic understanding of Nf2 gene function has advanced, it has so far been primarily restricted to Schwann cell-intrinsic events. Extracellular cues determining Schwann cell behavior with regard to schwannoma development remain unknown. Here we show pro-tumourigenic microenvironmental effects on Schwann cells where an altered axonal microenvironment in cooperation with injury signals contribute to a persistent regenerative Schwann cell response promoting schwannoma development. Specifically in genetically engineered mice following crush injuries on sciatic nerves, we found macroscopic nerve swellings in mice with homozygous nf2 gene deletion in Schwann cells and in animals with heterozygous nf2 knockout in both Schwann cells and axons. However, patient-mimicking schwannomas could only be provoked in animals with combined heterozygous nf2 knockout in Schwann cells and axons. We identified a severe re-myelination defect and sustained macrophage presence in the tumor tissue as major abnormalities. Strikingly, treatment of tumor-developing mice after nerve crush injury with medium-dose aspirin significantly decreased schwannoma progression in this disease model. Our results suggest a multifactorial concept for schwannoma formation-emphasizing axonal factors and mechanical nerve irritation as predilection site for schwannoma development. Furthermore, we provide evidence supporting the potential efficacy of anti-inflammatory drugs in the treatment of schwannomas

Tumors induce de novo steroid biosynthesis in T cells to evade immunity

Abstract: Tumors subvert immune cell function to evade immune responses, yet the complex mechanisms driving immune evasion remain poorly understood. Here we show that tumors induce de novo steroidogenesis in T lymphocytes to evade anti-tumor immunity. Using a transgenic steroidogenesis-reporter mouse line we identify and characterize de novo steroidogenic immune cells, defining the global gene expression identity of these steroid-producing immune cells and gene regulatory networks by using single-cell transcriptomics. Genetic ablation of T cell steroidogenesis restricts primary tumor growth and metastatic dissemination in mouse models. Steroidogenic T cells dysregulate anti-tumor immunity, and inhibition of the steroidogenesis pathway is sufficient to restore anti-tumor immunity. This study demonstrates T cell de novo steroidogenesis as a mechanism of anti-tumor immunosuppression and a potential druggable target