614 research outputs found
High-Energy Neutrino Astronomy
Kilometer-scale neutrino detectors such as IceCube are discovery instruments
covering nuclear and particle physics, cosmology and astronomy. Examples of
their multidisciplinary missions include the search for the particle nature of
dark matter and for additional small dimensions of space. In the end, their
conceptual design is very much anchored to the observational fact that Nature
accelerates protons and photons to energies in excess of and
eV, respectively. The cosmic ray connection sets the scale of cosmic
neutrino fluxes. In this context, we discuss the first results of the completed
AMANDA detector and the reach of its extension, IceCube. Similar experiments
are under construction in the Mediterranean. Neutrino astronomy is also
expanding in new directions with efforts to detect air showers, acoustic and
radio signals initiated by super-EeV neutrinos.Comment: 9 pages, Latex2e, uses ws-procs975x65standard.sty (included), 4
postscript figures. To appear in Proceedings of Thinking, Observing, and
Mining the Universe, Sorrento, Italy, September 200
The Money Mentors Program: Increasing Financial Literacy in Utah Youths
Utah 4-H and Fidelity Investments collaborated on a program for increasing the financial literacy of teens and children. The collaboration resulted in positive impacts for both Extension and Utah youths. Extension benefited through partnership with a corporation that provided content expertise, volunteers, and funding for a financial literacy program. Youths benefited from improved financial literacy. A Teens Reaching Youth (TRY) team approach was used for the training of 81 teens, who then taught 530 youths statewide. The curriculum addressed research-based financial concepts through activities and technologies that were interactive, appealing, and engaging. The program development and implementation processes may serve as models for other Extension programs, and the curriculum is free to download
Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking
Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake
Differences in Heart Disease Risk Perception and Actual Cardiac Risk in Men vs. Women
Differences in Heart Disease Risk Perception and Actual Cardiac Risk in Male vs. Female Cardiac Patients Amanda Dietz, Julie Borsack, Steve Martin, Kathy L. Hill, Thomas Meade, Stephen F. Crouse, FACSM, and John S. Green, FACSM Texas A&M University, College Station, TX (Sponsor: John S. Green, FACSM)
PURPOSE: To describe gender differences in both risk perception and actual coronary risk in patients with coronary artery disease (CAD). METHODS: 33 females and 67 males with documented CAD completed a questionnaire designed to assess CAD risk perception. They also underwent assessments for all ACSM risk factors. Five-point Likert scale responses to the question “Compared to others of your own age and gender, how would you rate your risk of ever having a heart attack?” were used to quantify CAD risk perception. To quantify actual risk, the number of ACSM risk markers for each subject was tabulated. It should be noted that, since all of the subjects had active CAD, they were all at high risk. Tabulations and Likert scale responses were compared using Chi-square analysis or Fisher’s Exact test with significance accepted at p\u3c0.05. To further assess risk perception accuracy, Chi-square analysis with pre-determined expected cell count percentages was used. RESULTS: Likert responses for perceived risk between genders were not significantly different but showed perception inaccuracies of the entire cohort. Only 41% of the subjects perceived their risk as “higher” or “much higher” than their peers while 27% perceived their risk as lower or much lower. 32% of the subjects perceived their risk to be the same as their peers. Comparison of risk marker number between genders was significantly different (Fisher’s exact test, p = .046) with males having 33% more markers than females. Chi-square analysis using an expected cell percentage of 75% in the “higher” Likert category, 25% in the “much higher” Likert category, and fractions of 1 in the other categories revealed significance (p\u3c.0001) with only 29.8% of subject responses in the “higher” category and 11.9% in the “much higher” category. The female cohort showed similar results with test percentages of 73% in the “higher” category and 27% in the “much higher” category. Responses were significantly different (p\u3c.0001) with only 30% choosing the “higher” category and 10% choosing the “much higher” category. CONCLUSIONS: Although significant differences in actual cardiac risk exist between genders in a cohort of cardiac patients, perceived risks are not significantly different. Both genders greatly underestimate their risk
Predictors of donor follow‐up after living donor liver transplantation
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108074/1/lt23912.pd
‘The International Teacher Leadership project,’ a case of international action research.
Copyright CARNThe paper arises from the International Teacher Leadership project, a research and development project involving researchers and practitioners in 14 European countries. The paper provides a conceptual exploration of the idea of teacher leadership and its role in educational reform, central to which is the idea that teachers, regardless of their level of power and organisational position, can engage in the leadership of enquiry-based development activity aimed at influencing their colleagues and embedding improved practices in their schools. The paper provides an outline of the project’s methodology which builds on that used in the Carpe Vitam Leadership for Learning project (Frost, 2008a). It is a form of collaborative
action research which is highly developmental and discursive. It seeks to identify principles, strategies and tools that can be applied in a range of cultural settings. The paper includes a thematic analysis of the cultural contexts and policy environments of the participating countries in order to identify the obstacles to teacher leadership and to inform the nature of the support strategies employed
Characterization of resistance to a potent D-peptide HIV entry inhibitor.
BACKGROUND: PIE12-trimer is a highly potent D-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to prevent the viral resistance pathway of stepwise accumulation of modest affinity-disrupting mutations. Such modest mutations would not affect PIE12-trimer potency and therefore not confer a selective advantage. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely extended timeframe (\u3e 1 year) in comparison to other entry inhibitors. Eventually, HIV developed resistance to PIE12-trimer by mutating Q577 in the gp41 pocket.
RESULTS: Using deep sequence analysis, we identified three mutations at Q577 (R, N and K) in our two PIE12-trimer resistant pools. Each point mutant is capable of conferring the majority of PIE12-trimer resistance seen in the polyclonal pools. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. A high-resolution X-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. The Q577 mutations in an NL4-3 backbone decreased viral growth rates. Fitness was ultimately rescued in resistant viral pools by a suite of compensatory mutations in gp120 and gp41, of which we identified seven candidates from our sequencing data.
CONCLUSIONS: These data show that PIE12-trimer exhibits a high barrier to resistance, as extended passaging was required to develop resistant virus with normal growth rates. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness, and candidate compensatory mutations in gp160 have been identified
Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study
Peer reviewedPublisher PD
Deposition of SnS Thin Films from Sn(II) Thioamidate Precursors
Two
thioamide pro-ligands, R<sup>1</sup>N(H)C(S)R<sup>2</sup> (R<sup>1</sup> = <i>t</i>-Bu, R<sup>2</sup> = i-Pr and
R<sup>1</sup> = i-Pr, R<sup>2</sup> = i-Pr), were synthesized by treatment
of the corresponding amides with Lawesson’s reagent. Reactions
of [Sn{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>2</sub>] with two molar
equivalents of each thioamide pro-ligand yielded the tin(II) thioamidate
species, bis(2-methyl-<i>N</i>-(1-methylethyl)-propanethioamide)tin(II)
and Bis[<i>N</i>-(1,1-dimethylethyl)-2-methylpropanethioamide]tin(II).
Both of the new tin compounds have been characterized by <sup>1</sup>H, <sup>13</sup>C{<sup>1</sup>H}, and <sup>119</sup>Sn NMR spectroscopy
and elemental analysis. In addition, the solid-state structure of
bis(2-methyl-<i>N</i>-(1-methylethyl)-propanethioamide)tin(II)
has been determined through a single crystal X-ray diffraction analysis
and shown to display a monomeric constitution in which the tin(II)
center occupies a distorted <i>pseudo</i> square pyramidal
geometry defined by the N<sub>2</sub>S<sub>2</sub> donors and the
stereochemically active lone pair. Both tin(II) derivatives have been
assessed for their potential as single source precursors to SnS by
TGA and by NMR spectroscopic analysis of the volatile organic products
produced during their thermolysis. Both compounds have been utilized
in the growth of thin films by aerosol-assisted chemical vapor deposition
(AACVD). These latter studies provided film growth at temperatures
as low as 200 °C. The films have been analyzed by PXRD, Raman
spectroscopy, XPS, AFM, and SEM and are shown to comprise primarily
the orthorhombic (Herzenbergite) phase of SnS, which is contaminated
by only low levels of residual carbon (<5 at %). Although further
films deposited onto Mo-coated substrates produced only limited photocurrents
when illuminated, these results demonstrate the potential of such
simple thioamidate derivatives to act as single source precursors
to useful metal sulfide thin film materials
Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter
Background: Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina. Methods & Results A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina-targeted (embryonic day 12.5) deletion of VAChT (VAChT(Six3-Cre-flox/flox)) and littermate controls at 5 and 12 months of age. VAChT(Six3-Cre-flox/flox) mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChT(Six3-Cre-flox/flox) mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses. Significance This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina
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