Asymmetric cyclopropanation of conjugated cyanosulfones using a novel cupreine organocatalyst: rapid access to d3-amino acids

An organocatalytic asymmetric synthesis of a novel, highly functionalised cyclopropane system furnished with versatile substituents and containing a quaternary centre is described. The process utilises a new bifunctional catalyst based on the cinchona alkaloid framework and the products made using this catalyst were obtained as single diastereoisomers, with very high enantioselectivities (up to 96% ee). We have also demonstrated that these resulting cyclopropanes are very useful synthetic intermediates to interesting products, such as the difficult to access d3-amino acids

Skeletal accumulation of fluorescently-tagged zoledronate is higher in animals with early stage chronic kidney disease

This work examines the skeletal accumulation of fluorescently-tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation 24-hours post-dose in animals with lower kidney function due to greater amounts of binding at individual surfaces.NIH F30 DK115162; NIH T32 AR065971; NIH P30 DK 07931

A longitudinal evaluation of food safety knowledge and attitudes among Ontario high school students following a food handler training program

The final publication is available at Elsevier via https://doi.org/10.1016/j.foodcont.2017.01.011 © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Youth are a unique audience for food safety education, in part due to low food safety knowledge. Although the effectiveness of such education has been explored for primary school and college students, no studies have assessed effectiveness among high school students specifically. We conducted a longitudinal intervention study in Ontario, Canada, between February and May 2015, to measure the baseline food safety knowledge and attitudes of high school students (n=119; from 8 classes in 4 high schools), and determine whether these factors improved following in-class delivery of a provincial standardized food handler training program. Linear mixed effects regression models were used to model within-student changes in knowledge scores and attitudes over time (i.e., circa 2 and 12 weeks post-intervention), and to investigate associations with student characteristics. At baseline, knowledge and attitudes were poor. Following training, overall knowledge was significantly greater than at baseline, although at three months post-intervention only knowledge of safe times and temperatures for cooking and storing food remained significantly higher than baseline. Following training, students were significantly less interested in learning about how to avoid foodborne disease. Other attitudes, as well as knowledge of cross-contamination prevention and disinfection procedures, remained unchanged. These findings suggest that delivering existing food handler training programs within high schools may be a feasible mechanism for food safety educators to improve students’ food safety knowledge, both overall and specific to safe times and temperatures, albeit potentially for short timeframes. Whether knowledge continues to decline beyond three months after training bears further investigation. As well, future research to investigate how students’ actual food safety practices may change following such training, and whether improvements in knowledge translate into reduced foodborne disease risk, is warranted.Ontario Ministry of Agriculture, Food and Rural Affairs' Food Safety Research Program || FS2013-1843 Canadian Institutes of Health Research || OOP-110788 Canadian Institutes of Health Research || MOP-114875 Additional support was provided via CIHR Public Health Agency of Canada Chairs in Applied Public Health (D. Hammond, S. Leatherdale)

University of California Research Seminar Network: A Prospectus

By webcasting the hundreds of seminars presented in the University of California system each week, UC educators hope to enhance the exchange of scientific information for their campuses and create the foundation for an international research seminar network

Coastal Ocean Processes : a science prospectus

CoOP (Coastal Ocean Processes) is an organization meant to study major interdisciplinary scientific problems in the coastal ocean. Its goal is "to obtain a new level of quantitative understanding of the processes that dominate the transformations, transport and fates of biologically, chemically and geologically important matter on the continental margin". Central to obtaining this understanding will be advances in observing and modeling the cross-shelf component of transport. More specific objectives are to understand 1) cross-margin exchanges, 2) air sea exchanges, 3) benthic-pelagic exchanges, 4) terrestrial inputs and 5) biological and chemical transformations within the water column. CoOP research will be carried out primarly through a series of process-oriented field studies, each involving about two years of measurements. Each of these field studies is to be initiated and defined through a community workshop. In addition to the process studies, CoOP will also involve modeling, long time series, exploratory studies, remote sensing, technological innovation, data archiving and communications. A CoOP pilot study has been approved for funding by the National Science Foundation, and funding will begin in 1992. The CoOP science effort is thus already underway.Funding was provided by the National Science Foundation under Grant No. OCE-9108993

UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis

\ua9 2024 The Author(s)Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies

Scaling Up the 2010 World Health Organization HIV Treatment Guidelines in Resource-Limited Settings: A Model-Based Analysis

Rochelle Walensky and colleagues use a model-based analysis to examine which of the 2010 WHO antiretroviral therapy guidelines should be implemented first in resource-limited settings by ranking them according to survival, cost-effectiveness, and equity

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

High intensity interval training exercise increases dopamine D2 levels and modulates brain dopamine signaling

BackgroundPrevious research has outlined the health benefits of exercise including its therapeutic potential for substance use disorders (SUD). These data have already been utilized and it is now common to find exercise as part of SUD treatment and relapse prevention programs. However, we need to better understand different exercise regimens and determine which would be the most beneficial for SUDs. Recently, high intensity interval training (HIIT) has gained attention in comparison with aerobic and resistance exercise. Little is known regarding the neurobiological mechanisms of HIIT, including its effects on dopamine signaling and receptor levels in the brain. The present study examined the effects of chronic HIIT exercise on dopamine signaling as measured by dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and tyrosine hydroxylase (TH) quantification in the brains of male and female rats as measured by [3H] SCH 23390 and [3H] spiperone autoradiography, and TH-immunoreactive optical density values.MethodsRats were separated in two groups: sedentary and HIIT exercise. Exercise was on a treadmill for 30 min daily (10 3 min cycles) for six weeks with progressive speed increased up to 0.8 mph (21.5 m/min).ResultsResults showed for D2R-like binding, a significant effect across the ventral caudate putamen (V CPU) between sexes, such that mean D2R-like binding was 14% greater for males than females. In the nucleus accumbens shell (Nac Shell), the HIIT Exercise rats showed 16% greater D2R-like binding as compared to the sedentary rats. No significant effects of HIIT exercise were found across groups for brain D1R-like binding levels or TH expression.ConclusionThese results suggest that HIIT exercise can modulate dopamine signaling by way of increased D2R. These findings support the premise that HIIT exercise plays an important role in dopamine signaling and, may provide a potential mechanism for how HIIT exercise can impact the brain and behavior