Wide band instantaneous coverage receiver concept for ALMA

We propose concept of frequency array receiver. Receiver input beam will be quasi-optically frequency multiplexed on several mixer pixels. All individual mixers will be operated simultaneously creating very large input bandwidth covering several atmospheric windows in high frequency resolution. This system allows to combine large bandwidth advantage of direct detecting with high frequency resolution of heterodyne system. We will discuss initial system concept, and report on mixer designs and their performance for building elements. In particularly we report DSB noise temperature below hf/k level at 260GHz mixer prototype. Sensitivity of such system in presents of atmospheric background will be evaluated

Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating alpha-Klotho Concentrations

The CKD-associated decline in soluble α-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of α-Klotho in the kidney. We examined the effect of anti-oxidant therapy on α-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (α-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. α-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 ± 14 ml/min/1.72 m2, 34 were male and mean age was 53.0 ± 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). α-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 ± 124.3 to 492.7 ± 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 ± 142.5 to 489.6 ± 120.3 pg/mL, P = 0.62). Changes in α-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti-oxidative therapy affected α-Klotho concentrations in patients with mild-moderate CKD

An altered gp100 peptide ligand with decreased binding by TCR and CD8α dissects T cell cytotoxicity from production of cytokines and activation of NFAT

Altered peptide ligands (APLs) provide useful tools to study T cell activation and potentially direct immune responses to improve treatment of cancer patients. To better understand and exploit APLs, we studied the relationship between APLs and T cell function in more detail. Here, we tested a broad panel of gp100280-288 APLs with respect to T cell cytotoxicity, production of cytokines, and activation of Nuclear Factor of Activated T cells (NFAT) by human T cells gene-engineered with a gp100-HLA-A2-specific TCRαβ. We demonstrated that gp100-specific cytotoxicity, production of cytokines, and activation of NFAT were not affected by APLs with single amino acid substitutions, except for an APL with an amino acid substitution at position 3 (APL A3), which did not elicit any T cell response. A gp100 peptide with a double amino acid mutation (APL S4S6) elicited T cell cytotoxicity and production of IFNγ, and to a lesser extent TNFα, IL-4, and IL-5, but not production of IL-2 and IL-10, or activation of NFAT. Notably, T cell receptor (TCR)-mediated functions showed decreases in sensitivities for S4S6 versus gp100 wild-type (wt) peptide, which were minor for cytotoxicity but at least a 1000-fold more prominent for the production of cytokines. TCR-engineered T cells did not bind A3-HLA-A2, but did bind S4S6-HLA-A2 although to a lowered extent compared to wt peptide-HLA-A2. Moreover, S4S6-induced T cell function demonstrated an enhanced dependency on CD8α. Taken together, most gp100 APLs functioned as agonists, but A3 and S4S6 peptides acted as a null ligand and partial agonist, respectively. Our results further suggest that TCR-mediated cytotoxicity can be dissected from production of cytokines and activation of NFAT, and that the agonist potential of peptide mutants relates to the extent of binding by TCR and CD8α. These findings may facilitate the design of APLs to advance the study of T cell activation and their use for therapeutic applications

Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition

MicroRNA (miRNA) sponges are transcripts with repeated miRNA antisense sequences that can sequester miRNAs from endogenous targets. MiRNA sponges are valuable tools for miRNA loss-of-function studies both in vitro and in vivo. We developed a fast and flexible method to generate miRNA sponges and tested their efficiency in various assays. Using a single directional ligation reaction we generated sponges with 10 or more miRNA binding sites. Luciferase and AGO2-immuno precipitation (IP) assays confirmed effective binding of the miRNAs to the sponges. Using a GFP competition assay we showed that miR-19 sponges with central mismatches in the miRNA binding sites are efficient miRNA inhibitors while sponges with perfect antisense binding sites are not. Quantification of miRNA sponge levels suggests that this is at least in part due to degradation of the perfect antisense sponge transcripts. Finally, we provide evidence that combined inhibition of miRNAs of the miR-17∼92 cluster results in a more effective growth inhibition as compared to inhibition of individual miRNAs. In conclusion, we describe and validate a method to rapidly generate miRNA sponges for miRNA loss-of-function studies

A Deployable 600-720GHz ALMA-TypeSideband-Separating Receiver Cartridge

Esta investigación, titulada “La autoestima y el desarrollo de las habilidades sociales en los alumnos de la Carrera de Administración Bancaria del Instituto Certus”, ha sido desarrollada con la finalidad de evaluar la relación que hay entre la autoestima y las habilidades sociales de los estudiantes de la Carrera de Administración Bancaria del Instituto Certus. Para este fin, fue necesario hacer un trabajo de campo definido dentro de un enfoque cuantitativo, cubriendo un alcance descriptivo y correlacional, además de seguir un diseño no experimental y transversal

Sideband separating mixer for 600-720 GHz for ALMA band 9 upgrade

For high-frequency observational bands like ALMA (Atacama Large Millimeter Array) Band 9 (600—720 GHz), which tend to be dominated by atmospheric noise, implementation of sideband-separating mixers can reduce, up to a factor of two, the integration time needed to reach a certain signal-to-noise ratio for spectral line observations. Because of very high oversubscription factor for observation in ALMA Band 9, an upgrade of the current Double Sideband (DSB) mixer to a Two Sideband (2SB) configuration is a promising option for future ALMA development. Here we present a developed 2SB mixer and a modified cartridge design. The 2SB mixer includes a waveguide RF hybrid block, which have been produced on a micro-milling machine and equipped with standard Band 9 SIS mixer devices. These two SIS mixers have been separately tested in DSB mode. The SSB noise temperature is within the ALMA requirements of 336 K over 80% of the band, and 500 K over the entire band. The 2SB mixer has the sideband rejection ratio better than 12 dB over the ful