A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

Lifetime determination of excited states in Cd-106

Two separate experiments using the Differential Decay Curve Method have been performed to extract mean lifetimes of excited states in 106 Cd. The inedium-spin states of interest were populated by the Mo-98(C-12, 4n) Cd-106 reaction performed at the Wright Nuclear Structure Lab., Yale University. From this experiment, two isomeric state mean lifetimes have been deduced. The low-lying states were populated by the Mo-96(C-13, 3n)Cd-106 reaction performed at the Institut fur Kernphysik, Universitat zu Koln. The mean lifetime of the I-pi = 2(1)(+) state was deduced, tentatively, as 16.4(9) ps. This value differs from the previously accepted literature value from Coulomb excitation of 10.43(9) ps

Identification of mixed-symmetry states in an odd-mass nearly-spherical nucleus

The low-spin structure of 93Nb has been studied using the (n,n' gamma) reaction at neutron energies ranging from 1.5 to 3.0 MeV and the 94Zr(p,2n gamma)93Nb reaction at bombarding energies from 11.5 to 19 MeV. States at 1779.7 and 1840.6 keV, respectively, are proposed as mixed-symmetry states associated with the coupling of a proton hole in the p_1/2 orbit to the 2+_1,ms state in 94Mo. These assignments are derived from the observed M1 and E2 transition strengths to the symmetric one-phonon states, energy systematics, spins and parities, and comparison with shell model calculations.Comment: 5 pages, 3 figure

The Intrinsic Origin of Spin Echoes in Dipolar Solids Generated by Strong Pi Pulses

In spectroscopy, it is conventional to treat pulses much stronger than the linewidth as delta-functions. In NMR, this assumption leads to the prediction that pi pulses do not refocus the dipolar coupling. However, NMR spin echo measurements in dipolar solids defy these conventional expectations when more than one pi pulse is used. Observed effects include a long tail in the CPMG echo train for short delays between pi pulses, an even-odd asymmetry in the echo amplitudes for long delays, an unusual fingerprint pattern for intermediate delays, and a strong sensitivity to pi-pulse phase. Experiments that set limits on possible extrinsic causes for the phenomena are reported. We find that the action of the system's internal Hamiltonian during any real pulse is sufficient to cause the effects. Exact numerical calculations, combined with average Hamiltonian theory, identify novel terms that are sensitive to parameters such as pulse phase, dipolar coupling, and system size. Visualization of the entire density matrix shows a unique flow of quantum coherence from non-observable to observable channels when applying repeated pi pulses.Comment: 24 pages, 27 figures. Revised from helpful referee comments. Added new Table IV, new paragraphs on pages 3 and 1

An intercontinental analysis of food safety culture in view of food safety governance and national values

Taking food safety culture into account is a promising way to improve food safety performance in the food industry. Food safety culture (FS-culture) research is expanding from an organisational perspective to include characteristics of the internal and external company environment. In this study, the prevailing food safety culture in 17 food companies from four countries on three continents (Africa, Asia and Europe) was assessed in view of food safety governance and national values. The internal environment characteristics, i.e. food safety vision, food safety program and food production system vulnerability, were also assessed. Statistical analysis revealed little variation in FS-culture scores between the companies within the same country. Overall the FS-culture for Greek and Zambian companies was scored proactive, while for Chinese and Tanzanian companies an active score was achieved. Both the internal and external company environment seemed to influence the prevailing FS-culture. Cluster analysis showed that Tanzanian and Zambian companies exhibited similarities in the implementation of food safety programs, and in their national values and food safety governance as compared to Greece and China. Food safety governance was reflected in the food safety programs and supportiveness of the organisation to food safety and hygiene. All cultural dimensions were correlated with risk perceptions, with masculinity and long-term orientation also significantly correlated with the enabling conditions and attitude. Understanding how national values and food safety governance approaches differently influence food safety culture is expected to enable formulation of best approaches tailored for companies operating in countries with different company environments, to improve food safety performance.</p

The Study of TeV Variability and Duty Cycle of Mrk 421 from 3 Years of Observations with the Milagro Observatory

TeV flaring activity with time scales as short as tens of minutes and an orphan TeV flare have been observed from the blazar Markarian 421 (Mrk 421). The TeV emission from Mrk 421 is believed to be produced by leptonic synchrotron self-Compton (SSC) emission. In this scenario, correlations between the X-ray and the TeV fluxes are expected, TeV orphan flares are hardly explained and the activity (measured as duty cycle) of the source at TeV energies is expected to be equal or less than that observed in X-rays if only SSC is considered. To estimate the TeV duty cycle of Mrk 421 and to establish limits on its variability at different time scales, we continuously observed Mrk 421 with the Milagro observatory. Mrk 421 was detected by Milagro with a statistical significance of 7.1 standard deviations between 2005 September 21 and 2008 March 15. The observed spectrum is consistent with previous observations by VERITAS. We estimate the duty cycle of Mrk 421 for energies above 1 TeV for different hypothesis of the baseline flux and for different flare selections and we compare our results with the X-ray duty cycle estimated by Resconi et al. 2009. The robustness of the results is discussed.Comment: 27 pages, 6 figures, ApJ accepte

Типові схеми використання офшорних та оншорних зон для зменшення податкового навантаження бізнесу в Україні

The proteasome is able to create spliced Ags, in which two distant parts of a protein are excised and ligated together to form a novel peptide, for presentation by MHC class I molecules. These noncontiguous epitopes are generated via a transpeptidation reaction catalyzed by the proteasomal active sites. Transpeptidation reactions in the proteasome follow explicit rules and occur particularly efficiently when the C-terminal ligation partner contains a lysine or arginine residue at the site of ligation. Lysine contains two amino groups that theoretically may both participate in ligation reactions, implying that potentially not only peptide but also isopeptide linkages could be formed. Using nuclear magnetic resonance spectroscopy, we demonstrate in the present study that the proteasome can use the ε-amino group of an N-terminal lysine residue in transpeptidation reactions to create a novel type of posttranslationally modified epitopes. We show that the overall efficiency of ε ligation is only 10-fold lower as compared with α ligation, suggesting that the proteasome can produce sufficient isopeptide Ag to evoke a T cell response. Additionally, we show that isopeptides are more stable toward further proteasomal processing than are normal peptides, and we demonstrate that isopeptides can bind to HLA-A2.1 and HLA-A3 with high affinity. These properties likely increase the fraction of ε-ligated peptides presented on the cell surface for CD8+ T cell surveillance. Finally, we show that isopeptide Ags are immunogenic in vivo. We postulate that ε ligation is a genuine posttranslational modification, suggesting that the proteasome can create a novel type of Ag that is likely to play a role in immunity

TeV Gamma-Ray Sources from a Survey of the Galactic Plane with Milagro

A survey of Galactic gamma-ray sources at a median energy of ~20 TeV has been performed using the Milagro Gamma Ray Observatory. Eight candidate sources of TeV emission are detected with pre-trials significance $>4.5\sigma$ in the region of Galactic longitude $l\in[30^\circ,220^\circ]$ and latitude $b\in[-10^\circ,10^\circ]$. Four of these sources, including the Crab nebula and the recently published MGRO J2019+37, are observed with significances $>4\sigma$ after accounting for the trials involved in searching the 3800 square degree region. All four of these sources are also coincident with EGRET sources. Two of the lower significance sources are coincident with EGRET sources and one of these sources is Geminga. The other two candidates are in the Cygnus region of the Galaxy. Several of the sources appear to be spatially extended. The fluxes of the sources at 20 TeV range from ~25% of the Crab flux to nearly as bright as the Crab.Comment: Submitted to Ap

Discovery of Localized Regions of Excess 10-TeV Cosmic Rays

An analysis of 7 years of Milagro data performed on a 10-degree angular scale has found two localized regions of excess of unknown origin with greater than 12 sigma significance. Both regions are inconsistent with gamma-ray emission with high confidence. One of the regions has a different energy spectrum than the isotropic cosmic-ray flux at a level of 4.6 sigma, and it is consistent with hard spectrum protons with an exponential cutoff, with the most significant excess at ~10 TeV. Potential causes of these excesses are explored, but no compelling explanations are found.Comment: Submitted to PhysRevLet

Search for very high energy gamma-rays from WIMP annihilations near the Sun with the Milagro Detector

The neutralino, the lightest stable supersymmetric particle, is a strong theoretical candidate for the missing astronomical ``dark matter''. A profusion of such neutralinos can accumulate near the Sun when they lose energy upon scattering and are gravitationally captured. Pair-annihilations of those neutralinos may produce very high energy (VHE, above $100 GeV$) gamma-rays. Milagro is an air shower array which uses the water Cherenkov technique to detect extensive air showers and is capable of observing VHE gamma-rays from the direction of the Sun with an angular resolution of $0.75^{\circ}$. Analysis of Milagro data with an exposure to the Sun of 1165 hours presents the first attempt to detect TeV gamma-rays produced by annihilating neutralinos captured by the Solar system and shows no statistically significant signal. Resulting limits that can be set on gamma-ray flux due to near-Solar neutralino annihilations and on neutralino cross-section are presented