NASA Lidar system support and MOPA technology demonstration

A series of lidar design and technology demonstration tasks in support of a CO2 lidar program is discussed. The first of these tasks is discussed in Section VI of this report under the heading of NASA Optical Lidar Design and it consists of detailed recommendations for the layout of a CO2 Doppler lidar incorporating then existing NASA optical components and mounts. The second phase of this work consisted of the design, development, and delivery to NASA of a novel acousto-optic laser frequency stabilization system for use with the existing NASA ring laser transmitter. The second major task in this program encompasses the design and experimental demonstration of a master oscillator-power amplifier (MOPA) laser transmitter utilizing a commercially available laser as the amplifier. The MOPA design including the low chirp master oscillator is discussed in detail. Experimental results are given for one, two and three pass amplification. The report includes operating procedures for the MOPA system

Aryl hydrocarbon receptor activation during in vitro and in vivo digestion of raw and cooked broccoli (brassica oleracea var. Italica)

Broccoli is rich in glucosinolates, which can be converted upon chewing and processing into Aryl hydrocarbon Receptor (AhR) ligands. Activation of AhR plays an important role in overall gut homeostasis but the role of broccoli processing on the generation of AhR ligands is still largely unknown. In this study, the effects of temperature, cooking method (steaming versus boiling), gastric pH and further digestion of broccoli on AhR activation were investigated in vitro and in ileostomy subjects. For the in vitro study, raw, steamed (t = 3 min and t = 6 min) and boiled (t = 3 min and t = 6 min) broccoli were digested in vitro with different gastric pH. In the in vivo ileostomy study, 8 subjects received a broccoli soup or a broccoli soup plus an exogenous myrosinase source. AhR activation was measured in both in vitro and in vivo samples by using HepG2-Lucia™ AhR reporter cells. Cooking broccoli reduced the AhR activation measured after gastric digestion in vitro, but no effect of gastric pH was found. Indole AhR ligands were not detected or detected at very low levels both after intestinal in vitro digestion and in the ileostomy patient samples, which resulted in no AhR activation. This suggests that the evaluation of the relevance of glucosinolates for AhR modulation in the gut cannot prescind from the way broccoli is processed, and that broccoli consumption does not necessarily produce substantial amounts of AhR ligands in the large intestine

Effect of a Short-Course Treatment with Synbiotics on Plasma p-Cresol Concentration in Kidney Transplant Recipients.

We evaluated whether a short-term course with synbiotics may lower plasma p-Cresol concentrations in kidney transplant patients (KTRs) who accumulate this uremic toxin both because of increased production by their dysbiotic gut microbiome and because of reduced elimination by the transplanted kidneys. METHODS: Thirty-six KTRs (29 males, mean age 49.6 ± 9.1 years) with transplant vintage > 12 months, stable graft function, and no episode of acute rejection or infection in the last 3 months were enrolled in this single-center, parallel-group, double-blinded, randomized (2:1 synbiotic to placebo) study. Synbiotic (Probinul Neutro, CadiGroup, Rome, Italy) or placebo was taken at home for 30 days, as 5 g powder packets dissolved in water three times a day far from meals. The main outcome measure was the decrease in total plasma p-Cresol measured by high-performance liquid chromatography at baseline and after 15 and 30 days of placebo or synbiotic treatment. RESULTS: After 15 and 30 days of treatment, plasma p-Cresol decreased by 40% and 33% from baseline (both p < 0.05), respectively, in the synbiotic group, whereas it remained stable in the placebo group. After 30 days of treatment, no significant change was observed in either group in renal function, glycemia, plasma lipids, or albumin concentration. Treatment was well tolerated and did not induce any change in stool characteristics. CONCLUSION: The results of this pilot study suggest that treatment with synbiotics may be effective to lower plasma p-Cresol concentrations in KTRs. Prospective larger scale, longer term studies are needed to establish whether cardiovascular prognosis could also be improved with this nutritional intervention

Strange Quark Contributions to Parity-Violating Asymmetries in the Backward Angle G0 Electron Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton and quasi-elastic electron-deuteron scattering at Q^2 = 0.22 and 0.63 GeV^2. They are sensitive to strange quark contributions to currents in the nucleon, and to the nucleon axial current. The results indicate strange quark contributions of < 10% of the charge and magnetic nucleon form factors at these four-momentum transfers. We also present the first measurement of anapole moment effects in the axial current at these four-momentum transfers.Comment: 5 pages, 2 figures, changed references, typo, and conten

Polymorphisms in the SOCS7 gene and glucose homeostasis traits

BACKGROUND: SOCS7 is a member of the suppressor of cytokine signaling family of proteins and is expressed in skeletal muscle and islets. SOCS7 deficient mice develop islet hyperplasia in the setting of increased insulin sensitivity and normal glucose tolerance. The objective of this study was to determine if variants in SOCS7 play a role in variation of glucose and insulin levels and the development of type 2 diabetes (T2DM). RESULTS: Five SOCS7 tagging SNPs were genotyped in diabetic and nondiabetic Old Order Amish. A case–control study was performed in T2DM (n = 145) and normal glucose tolerant (n = 358) subjects. Nominal associations were observed with T2DM and the minor alleles for rs8068600 (P = 0.01) and rs8074124 (P = 0.04); however, only rs8068600 remained significant after Bonferroni adjustment for multiple comparisons (P = 0.01). Among nondiabetic Amish (n = 765), no significant associations with glucose or insulin traits including fasting or 2 hour glucose and insulin from the oral glucose tolerance test, insulin or glucose area under the curve, Matsuda Index or HOMA-IR were found for any of the SNPs. CONCLUSION: In conclusion, genetic variants in the SOCS7 gene do not impact variation in glucose homeostasis traits and only minimally impact risk of T2DM in the Old Order Amish. Our study was not able to address whether rare variants that potentially impact gene function might influence T2DM risk

Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors

Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism (Mistry et al., 2016), but their molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, BQCA, in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human M1 mAChR. Interactions between the orthosteric agonists and the novel PAMs or BQCA suggested their allosteric effects were solely governed by modulation of agonist affinity. The greatest degree of positive co-operativity was observed with higher efficacy agonists, whereas minimal potentiation was observed when the modulators were tested against the lower efficacy agonist, xanomeline. Each PAM was investigated for its effects on the endogenous agonist, ACh, on three different signalling pathways, (ERK1/2 phosphorylation, IP1 accumulation and β-arrestin-2 recruitment), revealing that the allosteric potentiation generally tracked with the efficiency of stimulus-response coupling and that there was little pathway bias in the allosteric effects. Thus, despite the identification of novel allosteric scaffolds targeting the M1 mAChR, the molecular mechanism of action of these compounds is largely consistent with a model of allostery previously described for BQCA, suggesting that this may be a more generalized mechanism for M1 mAChR PAM effects than previously appreciated

4-Phenylpyridin-2-one derivatives: a novel class of positive allosteric modulator of the M1 muscarinic acetylcholine receptor

Positive allosteric modulators (PAMs) of the M1 muscarinic acetylcholine receptor (M1 mAChR) are a promising strategy for the treatment of the cognitive deficits associated with diseases including Alzheimer’s and schizophrenia. Herein, we report the design, synthesis, and characterization of a novel family of M1 mAChR PAMs. The most active compounds of the 4-phenylpyridin-2-one series exhibited comparable binding affinity to the reference compound, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (BQCA) (1), but markedly improved positive cooperativity with acetylcholine, and retained exquisite selectivity for the M1 mAChR. Furthermore, our pharmacological characterization revealed ligands with a diverse range of activities, including modulators that displayed both high intrinsic efficacy and PAM activity, those that showed no detectable agonism but robust PAM activity and ligands that displayed robust allosteric agonism but little modulatory activity. Thus, the 4-phenylpyridin-2-one scaffold offers an attractive starting point for further lead optimization

Transverse Beam Spin Asymmetries at Backward Angles in Elastic Electron-Proton and Quasi-elastic Electron-Deuteron Scattering

We have measured the beam-normal single-spin asymmetries in elastic scattering of transversely polarized electrons from the proton, and performed the first measurement in quasi-elastic scattering on the deuteron, at backward angles (lab scattering angle of 108 degrees) for Q2 = 0.22 GeV^2/c^2 and 0.63 GeV^2/c^2 at beam energies of 362 MeV and 687 MeV, respectively. The asymmetry arises due to the imaginary part of the interference of the two-photon exchange amplitude with that of single photon exchange. Results for the proton are consistent with a model calculation which includes inelastic intermediate hadronic (piN) states. An estimate of the beam-normal single-spin asymmetry for the scattering from the neutron is made using a quasi-static deuterium approximation, and is also in agreement with theory

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method