66 research outputs found
Building Legal Competency: Foundations for a More Effective Criminology and Criminal Justice Discipline
This article argues for the need to build legal competency in the discipline of criminal justice and criminology through incorporating law courses in its PhD program curriculum, whether as black letter law (i.e. criminal law, criminal procedure, courts), sociology of law, or socio-legal studies (i.e. law and society courses). Through requiring law courses as a necessary and integral part of the curriculum, and recognizing the mainstream impact of these courses, the discipline stands to enrich the field of legal studies in criminology and criminal justice. The disciplineâs need and demand for law trained tenure track faculty with PhD credentials can only be met through consistent law course offerings
PPARα Is Essential for Microparticle-Induced Differentiation of Mouse Bone Marrow-Derived Endothelial Progenitor Cells and Angiogenesis
BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for neovascularization. We hypothesized that microparticles (MPs), small fragments generated from the plasma membrane, can activate angiogenic programming of EPCs. METHODOLOGY/PRINCIPAL FINDINGS: We studied the effects of MPs obtained from wild type (MPs(PPARalpha+/+)) and knock-out (MPs(PPARalpha-/-)) mice on EPC differentiation and angiogenesis. Bone marrow-derived cells were isolated from WT or KO mice and were cultured in the presence of MPs(PPARalpha+/+) or MPs(PPARalpha-/-) obtained from blood of mice. Only MPs(PPARalpha+/+) harboring PPAR(alpha) significantly increased EPC, but not monocytic, differentiation. Bone marrow-derived cells treated with MPs(PPARalpha+/+) displayed increased expression of pro-angiogenic genes and increased in vivo angiogenesis. MPs(PPARalpha+/+) increased capillary-like tube formation of endothelial cells that was associated with enhanced expressions of endothelial cell-specific markers. Finally, the effects of MPs(PPARalpha+/+) were mediated by NF-kappaB-dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: Our results underscore the obligatory role of PPARalpha carried by MPs for EPC differentiation and angiogenesis. PPARalpha-NF-kappaB-Akt pathways may play a pivotal stimulatory role for neovascularization, which may, at least in part, be mediated by bone marrow-derived EPCs. Improvement of EPC differentiation may represent a useful strategy during reparative neovascularization
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A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18â19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10â80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR âcoreâ reveals two different velocities in the scintillation pattern: a primary velocity of ~20â40 msâ1 with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of ~110 msâ1 with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported
Counteranion-Dependent Reaction Pathways in the Protonation of Cationic RutheniumâVinylidene Complexes
The tetraphenylborate salts of the cationic vinylidene complexes [Cp*Ru=C=CHR(iPr2PNHPy)]+ (R = p-C6H4CF3 (1a-BPh4), Ph (1b-BPh4), p-C6H4CH3 (1c- BPh4), p-C6H4Br (1d-BPh4), tBu (1e-BPh4), H (1f-BPh4)) have been protonated using an excess of HBF4·OEt2 in CD2Cl2, furnishing the dicationic carbyne complexes [Cp*RuâĄCCH2R(iPr2PNHPy)]2+ (R = p-C6H4CF3 (2a), Ph (2b), p-C6H4CH3 (2c), p-C6H4Br (2d), tBu (2e), H (2f)), which were characterized in solution at low temperature by NMR spectroscopy. The corresponding reaction of the chloride salts 1a-Cl, 1b-Cl, 1c-Cl, and 1d-Cl followed a different pathway, instead affording the novel alkene complexes [Cp*RuCl(Îș1(N),η2(C,C)-C5H4N-NHPiPr2CH=CHR)][BF4] (3aâd). In these species, the entering proton is located at the α- carbon atom of the former vinylidene ligand, which also forms a PâC bond with the phosphorus atom of the iPr2PNHPy ligand. To shed light on the reaction mechanism, DFT calculations have been performed by considering several protonation sites. The computational results suggest metal protonation followed by insertion. The coordination of chloride to ruthenium leads to alkenyl species which can undergo a PâC coupling to yield the corresponding alkene complexes. The noncoordinating nature of [BPh4]â does not allow the stabilization of the unsaturated species coming from the insertion step, thus preventing this alternative pathway
Counteranion and Solvent Assistance in Ruthenium-Mediated Alkyne to Vinylidene Isomerizations
The complex [Cp*RuCl(iPr2PNHPy)] (1) reacts with 1-alkynes HCâĄCR (R = COOMe, C6H4CF3) in
dichloromethane furnishing the corresponding vinylidene complexes [Cp*RuâĄCâĄCHR(iPr2PNHPy)]Cl (R = COOMe (2a-
Cl), C6H4CF3 (2b-Cl)), whereas reaction of 1 with NaBPh4 in MeOH followed by addition of HCâĄCR (R = COOMe,
C6H4CF3) yields the metastable Ï-alkyne complexes [Cp*Ru(η2-HCâĄCR)(iPr2PNHPy)][BPh4] (R = COOMe (3a-BPh4),
C6H4CF3 (3b-BPh4)). The transformation of 3a-BPh4/3b-BPh4 into their respective vinylidene isomers in dichloromethane is
very slow and requires hours to its completion. However, this process is accelerated by addition of LiCl in methanol solution.
Reaction of 1 with HCâĄCR (R = COOMe, C6H4CF3) in MeOH goes through the intermediacy of the Ï-alkyne complexes
[Cp*Ru(η2-HCâĄCR)(iPr2PNHPy)]Cl (R = COOMe (3a-Cl), C6H4CF3 (3b-Cl)), which rearrange to vinylidenes in minutes,
i.e., much faster than their counterparts containing the [BPh4]â anion. The kinetics of these isomerizations has been studied in
solution by NMR. With the help of DFT studies, these observations have been interpreted in terms of chloride- and methanolassisted
hydrogen migrations. Calculations suggest participation of a hydridoâalkynyl intermediate in the process, in which the
hydrogen atom can be transferred from the metal to the ÎČ-carbon by means of species with weak basic character acting as proton
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Design, construction, and functional characterization of a tRNA neochromosome in yeast
Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the âŒ190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs
Design, construction, and functional characterization of a tRNA neochromosome in yeast
Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the âŒ190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs
Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.
AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals
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