Hyperpolarization of cis-15N,15N'-azobenzene by parahydrogen at ultralow magnetic fields

Development of the methods to exploit nuclear hyperpolarization and search for molecules whose nuclear spins can be efficiently hyperpolarized is an active area in nuclear magnetic resonance. Of particular interest are those molecules that have long nuclear relaxation times, making them to be suitable candidates as contrast agents in magnetic resonance imaging. In this work, we present a detailed study of SABRE SHEATH (Signal Amplification By Reversible Exchange in Shield Enabled Alignment Transfer to Heteronuclei) experiments of 15N,15N' azobenzene. In SABRE SHEATH experiments nuclear spins of the target are hyperpolarized by transfer of spin polarization from parahydrogen at ultralow fields during a reversible chemical process. The studied system is complicated, and we are concerned only about a subset of the data, presenting details for the molecules that experience fast chemical exchange at the catalytic complex and thus are involved in polarizing the free azobenzene. Azobenzene exists in two isomers trans- and cis-. We show that all nuclear spins in cis-azobenzene can be efficiently hyperpolarized by SABRE at suitable magnetic fields. Enhancement factors (relative to 9.4 T) reach several thousands of times for 15N spins and a few tens of times for the 1H spins. There are two approaches to observe either hyperpolarized magnetization of 15N/1H spins or hyperpolarized singlet order of the 15N spin pair. We compare these approaches and present the field dependencies of SABRE experiments for them. No hyperpolarization of trans 15N,15N' azobenzene was observed. The results presented here will be useful for further experiments where hyperpolarized cis-15N,15N' azobenzene is switched by light to trans 15N,15N' azobenzene for storing the produced hyperpolarization in the long-lived spin state of the 15N pair of trans-15N,15N' azobenzene

Visualization of NLP Extractions

The goal of this project is to design a visualization system for information extracted from large amounts of unstructured text. The importance of the project is for the system to display information in a more informative way than simple highlighting of the raw text. The data is obtained from a program that scans multiple files for entities and extracts the information in said files pertaining to those entities. The entities that the program scans for includes people, organizations, locations, dates, incidents and any relative key words. The information is extracted and stored in JSON files, specifically in a format that can be recognized by the visualization tool. The tool used is Exhibit 3.0 by Simile Widgets and is shown below, Figure 1 displaying the map and Figure 2 comparing the points. Exhibits displays the inputted data out on a map, using plots to show which locations had more frequent occurrences. The anticipated results are that the visualization system allows researchers to better understand the information being returned.https://scholarscompass.vcu.edu/capstone/1032/thumbnail.jp

A C/EBPα-Wnt connection in gut homeostasis and carcinogenesis

We explored the connection between C/EBPα (CCAAT/enhancer-binding protein α) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPα was expressed in human and murine intestinal epithelia in the transit-amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APC(Min/+) polyps, C/EBPα was absent in the nuclear β-catenin-positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPα KO in murine gut epithelia increased tumor volume. C/EBPα deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of β-catenin in organoids attenuated C/EBPα expression, and ectopic C/EBPα expression in HCT116 cells abrogated proliferation. C/EBPα expression accompanied differentiation of the colon cancer cell line Caco-2, whereas β-catenin stabilization suppressed C/EBPα. These data suggest homeostatic and oncogenic suppressor functions of C/EBPα in the gut by restricting Wnt signaling

Hope Agency and Hope Pathways as Potential Mediators of Trauma Exposure and Psychological Adjustment in Emerging Adults

The present study examined hope as a mediator between trauma exposure and negative affective conditions in 490 college students. Hope agency, but not hope pathways, mediated some of the association. Trauma exposure maintained a significant association with negative affective conditions. Implications for counselors working with trauma-exposed college students are discussed

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the <it>Cox-2 </it>gene is up-regulated in the gastric mucosa during <it>H. pylori </it>infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an <it>in vivo </it>model, thereby identifying potential targets for the study of the role of Cox- 2 in <it>H. pylori </it>pathogenesis and the initiation of pre- cancerous changes.</p> <p>Results</p> <p>Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after <it>H. pylori </it>infection. <it>H. pylori </it>infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of <it>H. pylori </it>infection. The Cox-2 dependent subset included those influencing gastric physiology (<it>Gastrin, Galr1</it>), epithelial barrier function (<it>Tjp1, connexin45, Aqp5</it>), inflammation (<it>Icam1</it>), apoptosis (<it>Clu</it>) and proliferation (<it>Gdf3, Igf2</it>). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression.</p> <p>Conclusion</p> <p>This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by <it>H. pylori </it>infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.</p

Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a

OBJECTIVE: In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS: Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS: At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS: SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-β-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01285401. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS treated with SC IFN-β-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status

An interactive web-based educational tool improves detection and delineation of Barrett’s esophagus related neoplasia

Background & Aims: Endoscopic detection of early Barrett’s esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. Methods: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett’s esophagus (NDBE). Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase 1, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared assessors interpretations with those from experts . These data informed selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. Results: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P [less than].001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all P [less than].001). Scores improved independent of assessors’ country of origin or level of endoscopic experience

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations