Origin of Enantioselection in Chiral Alcohol Oxidation Catalyzed by Pd[(-)-sparteine]Cl2

A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl2-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl2 prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl2 to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) â-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl-] and [H+] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured krel values when using the extracted constants. Besides a factor of 10 difference between the relative rates of â-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides

Diffusion tensor imaging and tractwise fractional anisotropy statistics: quantitative analysis in white matter pathology

<p>Abstract</p> <p>Background</p> <p>Information on anatomical connectivity in the brain by measurements of the diffusion of water in white matter tracts lead to quantification of local tract directionality and integrity.</p> <p>Methods</p> <p>The combination of connectivity mapping (fibre tracking, FT) with quantitative diffusion fractional anisotropy (FA) mapping resulted in the approach of results based on group-averaged data, named tractwise FA statistics (TFAS). The task of this study was to apply these methods to group-averaged data from different subjects to quantify differences between normal subjects and subjects with defined alterations of the corpus callosum (CC).</p> <p>Results</p> <p>TFAS exhibited a significant FA reduction especially in the CC, in agreement with region of interest (ROI)-based analyses.</p> <p>Conclusion</p> <p>In summary, the applicability of the TFAS approach to diffusion tensor imaging studies of normal and pathologically altered brains was demonstrated.</p

Enhanced heterosexual transmission hypothesis for the origin of pandemic HIV-1.

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CCR2 of Tumor Microenvironmental Cells Is a Relevant Modulator of Glioma Biology.

Glioblastoma multiforme (GBM) shows a high influx of tumor-associated macrophages (TAMs). The CCR2/CCL2 pathway is considered a relevant signal for the recruitment of TAMs and has been suggested as a therapeutic target in malignant gliomas. We found that TAMs of human GBM specimens and of a syngeneic glioma model express CCR2 to varying extents. Using a Ccr2-deficient strain for glioma inoculation revealed a 30% reduction of TAMs intratumorally. This diminished immune cell infiltration occurred with augmented tumor volumes likely based on increased cell proliferation. Remaining TAMs in Ccr2-/- mice showed comparable surface marker expression patterns in comparison to wildtype mice, but expression levels of inflammatory transcription factors (Stat3, Irf7, Cox2) and cytokines (Ifnβ, Il1β, Il12α) were considerably affected. Furthermore, we demonstrated an impact on blood vessel integrity, while vascularization of tumors appeared similar between mouse strains. The higher stability and attenuated leakiness of the tumor vasculature imply improved sustenance of glioma tissue in Ccr2-/- mice. Additionally, despite TAMs residing in the perivascular niche in Ccr2-/- mice, their pro-angiogenic activity was reduced by the downregulation of Vegf. In conclusion, lacking CCR2 solely on tumor microenvironmental cells leads to enhanced tumor progression, whereby high numbers of TAMs infiltrate gliomas independently of the CCR2/CCL2 signal

Crossing the Dripline to 11N Using Elastic Resonance Scattering

The level structure of the unbound nucleus 11N has been studied by 10C+p elastic resonance scattering in inverse geometry with the LISE3 spectrometer at GANIL, using a 10C beam with an energy of 9.0 MeV/u. An additional measurement was done at the A1200 spectrometer at MSU. The excitation function above the 10C+p threshold has been determined up to 5 MeV. A potential-model analysis revealed three resonance states at energies 1.27 (+0.18-0.05) MeV (Gamma=1.44 +-0.2 MeV), 2.01(+0.15-0.05) MeV, (Gamma=0.84 +-$0.2 MeV) and 3.75(+-0.05) MeV, (Gamma=0.60 +-0.05 MeV) with the spin-parity assignments I(pi) =1/2+, 1/2- and 5/2+, respectively. Hence, 11N is shown to have a ground state parity inversion completely analogous to its mirror partner, 11Be. A narrow resonance in the excitation function at 4.33 (+-0.05) MeV was also observed and assigned spin-parity 3/2-.Comment: 14 pages, 9 figures, twocolumn Accepted for publication in PR

Comparative whole genome sequence analysis of the carcinogenic bacterial model pathogen Helicobacter felis

The gram-negative bacterium Helicobacter felis naturally colonizes the gastric mucosa of dogs and cats. Due to its ability to persistently infect laboratory mice, H. felis has been used extensively to experimentally model gastric disorders induced in humans by H. pylori. We determined the 1.67 Mb genome sequence of H. felis using combined Solexa and 454 pyrosequencing, annotated the genome, and compared it with multiple previously published Helicobacter genomes. About 1,063 (63.6%) of the 1,671 genes identified in the H. felis genome have orthologues in H. pylori, its closest relative among the fully sequenced Helicobacter species. Many H. pylori virulence factors are shared by H. felis: these include the gamma-glutamyl transpeptidase GGT, the immunomodulator NapA, and the secreted enzymes collagenase and HtrA. Helicobacter felis lacks a Cag pathogenicity island and the vacuolating cytotoxin VacA but possesses a complete comB system conferring natural competence. Remarkable features of the H. felis genome include its paucity of transcriptional regulators and an extraordinary abundance of chemotaxis sensors and restriction/modification systems. Helicobacter felis possesses an episomally replicating 6.7-kb plasmid and harbors three chromosomal regions with deviating GC content. These putative horizontally acquired regions show homology and synteny with the recently isolated H. pylori plasmid pHPPC4 and homology to Campylobacter bacteriophage genes (transposases, structural, and lytic genes), respectively. In summary, the H. felis genome harbors a variety of putative mobile elements that are unique among Helicobacter species and may contribute to this pathogen's carcinogenic properties.Publisher PDFPeer reviewe

Observation of enhanced chiral asymmetries in the inner-shell photoionization of uniaxially oriented methyloxirane enantiomers

Most large molecules are chiral in their structure: they exist as two enantiomers, which are mirror images of each other. Whereas the rovibronic sublevels of two enantiomers are almost identical, it turns out that the photoelectric effect is sensitive to the absolute configuration of the ionized enantiomer - an effect termed Photoelectron Circular Dichroism (PECD). Our comprehensive study demonstrates that the origin of PECD can be found in the molecular frame electron emission pattern connecting PECD to other fundamental photophysical effects as the circular dichroism in angular distributions (CDAD). Accordingly, orienting a chiral molecule in space enhances the PECD by a factor of about 10

Alcohol-induced retrograde facilitation renders witnesses of crime less suggestible to misinformation

RATIONALE: Research has shown that alcohol can have both detrimental and facilitating effects on memory: intoxication can lead to poor memory for information encoded after alcohol consumption (anterograde amnesia) and may improve memory for information encoded before consumption (retrograde facilitation). This study examined whether alcohol consumed after witnessing a crime can render individuals less vulnerable to misleading post-event information (misinformation). METHOD: Participants watched a simulated crime video. Thereafter, one third of participants expected and received alcohol (alcohol group), one third did not expect but received alcohol (reverse placebo), and one third did not expect nor receive alcohol (control). After alcohol consumption, participants were exposed to misinformation embedded in a written narrative about the crime. The following day, participants completed a cued-recall questionnaire about the event. RESULTS: Control participants were more likely to report misinformation compared to the alcohol and reverse placebo group. CONCLUSION: The findings suggest that we may oversimplify the effect alcohol has on suggestibility and that sometimes alcohol can have beneficial effects on eyewitness memory by protecting against misleading post-event information

New μs isomers in Tz=1 nuclei produced in the 112Sn(63A MeV)+natNi reaction

Expérience GANIL, équipement SISSI/LISE