Measurement of the Elastic Magnetic Form Factor of ^3He at High Momentum Transfer(Abstracts of Doctoral Dissertations,Annual Report(from April 1999 to March 2000))

New measurements of the ^3He elastic magnetic form factor have extended our knowledge of the momentum transfer dependence out to Q^2 of 42.6 fm^. Data were also acquired in the region of the first diffraction minimum. These data are important for testing models of the nucleon-nucleon potential and for our understanding of non-nucleonic effects in the three-body system. The results of several three-body calculations are compared to these data. No existing three-body calculation can explain all of these data including previous form factor data for ^3He and ^3H, consistently

Gluon polarization measurements and the possible role of diffractive process in the transverse single spin asymmetry measurements in RHIC-PHENIX

Two selected topics from the latest RHIC spin results are discussed here. For the transversely polarized spin program, an unexpectedly large single spin asymmetry in the very forward neutron production observed in polarized proton + nucleus collisions at √s = 200 GeV is discussed in this document. For the longitudinal program, the latest highlights from the measurements on the gluon spin components of the proton spin is discussed. After a decade of continuous efforts to hunt for the gluon polarization, the RHIC collaboration is about to catch the tail of the experimental evidence that gluon carries substantially large portion of the proton spin

Positive allosteric modulation of the calcium-sensing receptor by physiological concentrations of glucose

The calcium-sensing receptor (CaSR) is activated by various cations, cationic compounds, and amino acids. In the present study we investigated the effect of glucose on CaSR in HEK293 cells stably expressing human CaSR (HEK-CaSR cells). When glucose concentration in the buffer was raised from 3 to 25 mM, a rapid elevation of cytoplasmic Ca2+ concentration ([Ca2+](c)) was observed. This elevation was immediate and transient and was followed by a sustained decrease in [Ca2+](c). The effect of glucose was detected at a concentration of 4 mM and reached its maximum at 5 mM. 3-O-Methylglucose, a non-metabolizable analogue of glucose, reproduced the effect of glucose. Sucrose also induced an elevation of [Ca2+](c) in HEK-CaSR cells. Similarly, sucralose was nearly as effective as glucose in inducing elevation of [Ca2+](c). Glucose was not able to increase [Ca2+](c) in the absence of extracellular Ca2+. The effect of glucose on [Ca2+](c) was inhibited by NPS-2143, an allosteric inhibitor of CaSR. In addition, NPS-2143 also inhibited the [Ca2+](c) responses to sucralose and sucrose. Glucose as well as sucralose decreased cytoplasmic cAMP concentration in HEK-CaSR cells. The reduction of cAMP induced by glucose was blocked by pertussis toxin. Likewise, sucralose reduced [cAMP](c). Finally, glucose increased [Ca2+](c) in PT-r parathyroid cells and in Madin-Darby canine kidney cells, both of which express endogenous CaSR. These results indicate that glucose acts as a positive allosteric modulator of CaSR

Identification of Antigenic Site Within hsc 70 by Serum Autoantibody in Patients with Cancer-associated Retinopathy

In our previous studies, both recoverin and heat shock cognate protein 70 (hsc 70) were found as autoantigens recognized by sera from four patients with cancer-associated retinopathy (CAR) . In the present study on the mole-cular mechanism of antibody generation in CAR, we identified the antigenic site within hsc 70 by the patients\u27 sera using deletion mutants of hsc 73. We expressed a series of deletion mutants of hsc 73 proteins and subjected then to western blot analysis. In western blot analysis, CAR patient\u27s serum reacted with wild type hsp 70, but not with the C-terminal truncated mutants. This data demonstrated that the antigenic site was located within the C-terminus region of hsc 73 as identified by CAR patient\u27s serum

Lactisole: an inhibitor of the glucose-sensing receptor T1R3 expressed in pancreatic B-cells

Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic beta-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was similar to 4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+](c)) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP](c)) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+](c) and [cAMP](c). Lactisole attenuated the sucralose-induced increase in [Ca2+](c) but did not affect the elevation of [cAMP](c). Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic beta-cells

Elucidating colorectal cancer-associated bacteria through profiling of minimally perturbed tissue-associated microbiota

Sequencing-based interrogation of gut microbiota is a valuable approach for detecting microbes associated with colorectal cancer (CRC); however, such studies are often confounded by the effect of bowel preparation. In this study, we evaluated the viability of identifying CRC-associated mucosal bacteria through centimeter-scale profiling of the microbiota in tumors and adjacent noncancerous tissue from eleven patients who underwent colonic resection without preoperative bowel preparation. High-throughput 16S rRNA gene sequencing revealed that differences between on- and off-tumor microbiota varied considerably among patients. For some patients, phylotypes affiliated with genera previously implicated in colorectal carcinogenesis, as well as genera with less well-understood roles in CRC, were enriched in tumor tissue, whereas for other patients, on- and off-tumor microbiota were very similar. Notably, the enrichment of phylotypes in tumor-associated mucosa was highly localized and no longer apparent even a few centimeters away from the tumor. Through short-term liquid culturing and metagenomics, we further generated more than one-hundred metagenome-assembled genomes, several representing bacteria that were enriched in on-tumor samples. This is one of the first studies to analyze largely unperturbed mucosal microbiota in tissue samples from the resected colons of unprepped CRC patients. Future studies with larger cohorts are expected to clarify the causes and consequences of the observed variability in the emergence of tumor-localized microbiota among patients

The RHIC Spin Program: Achievements and Future Opportunities

This document summarizes recent achievements of the RHIC spin program and their impact on our understanding of the nucleon's spin structure, i.e. the individual parton (quark and gluon) contributions to the helicity structure of the nucleon and to understand the origin of the transverse spin phenomena. Open questions are identified and a suite of future measurements with polarized beams at RHIC to address them is laid out. Machine and detector requirements and upgrades are briefly discussed

Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial

Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760

Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

BACKGROUND:Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS:The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+) ([Ca(2+)](c)) and cAMP ([cAMP](c)) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+)](c). The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+)](c) response. The effect of sucralose on [Ca(2+)](c) was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q) inhibitor. Sucralose also induced sustained elevation of [cAMP](c), which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS:Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+) and cAMP-dependent mechanisms

Measurement of very forward particle production at RHIC with √s=510 GeV proton-proton collisions

The Relativistic Heavy Ion Collider forward (RHICf) experiment has measured neutral particles produced in the very forward direction in the √s=510 GeV proton-proton collisions at RHIC in June 2017. The production cross sections of these particles are crucial to understand the hadronic interaction relevant to the air shower development at the cosmic-ray equivalent energy of 1.4×10$^{14}$ eV, just below the energy of the knee. Together with the data at LHC, accelerator data can cover the interaction in the cosmic-ray energy of 10$^{14}$ eV to 10$^{17}$ eV. In addition, RHICf is able to improve the former measurements of single-spin asymmetry in the polarized proton- proton collisions that is sensitive to the fundamental process of the meson exchange. Common data taking with the STAR experiment will shed light on the unexplored low mass diffraction process