190 research outputs found
Ab Initio Estimates of the Size of the Observable Universe
When one combines multiverse predictions by Bousso, Hall, and Nomura for the
observed age and size of the universe in terms of the proton and electron
charge and masses with anthropic predictions of Carter, Carr, and Rees for
these masses in terms of the charge, one gets that the age of the universe
should be roughly the inverse 64th power, and the cosmological constant should
be around the 128th power, of the proton charge. Combining these with a further
renormalization group argument gives a single approximate equation for the
proton charge, with no continuous adjustable or observed parameters, and with a
solution that is within 8% of the observed value. Using this solution gives
large logarithms for the age and size of the universe and for the cosmological
constant that agree with the observed values within 17%.Comment: 10 pages, LaTe
The BRCA2 c.68-7TÂ >Â A variant is not pathogenic: A model for clinical calibration of spliceogenicity.
Although the spliceogenic nature of the BRCA2 c.68-7T>A variant has been demonstrated, its association with cancer risk remains ontroversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636
individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T>A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 x 10-115. There was neither evidence for
increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T>A. Genetic and quantitative
transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants
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Diborane Reductions of CO2 and CS2 Mediated by Dicopper μ-Boryl Complexes of a Robust Bis(phosphino)-1,8-naphthyridine Ligand.
A dinucleating 1,8-naphthyridine ligand featuring fluorene-9,9-diyl-linked phosphino side arms (PNNPFlu) was synthesized and used to obtain the cationic dicopper complexes 2, [(PNNPFlu)Cu2(μ-Ph)][NTf2]; [NTf2] = bis(trifluoromethane)sulfonimide, 6, [(PNNPFlu)Cu2(μ-CCPh)][NTf2], and 3, [(PNNPFlu)Cu2(μ-OtBu)][NTf2]. Complex 3 reacted with diboranes to afford dicopper μ-boryl species (4, with μ-Bcat; cat = catecholate and 5, with μ-Bpin; pin = pinacolate) that are more reactive in C(sp)-H bond activations and toward activations of CO2 and CS2, compared to dicopper μ-boryl complexes supported by a 1,8-naphthyridine-based ligand with di(pyridyl) side arms. The solid-state structures and DFT analysis indicate that the higher reactivities of 4 and 5 relate to changes in the coordination sphere of copper, rather than to perturbations on the Cu-B bonding interactions. Addition of xylyl isocyanide (CNXyl) to 4 gave 7, [(PNNPFlu)Cu2(μ-Bcat)(CNXyl)][NTf2], demonstrating that the lower coordination number at copper is chemically significant. Reactions of 4 and 5 with CO2 yielded the corresponding dicopper borate complexes (8, [(PNNPFlu)Cu2(μ-OBcat)][NTf2]; 9, [(PNNPFlu)Cu2(μ-OBpin)][NTf2]), with 4 demonstrating catalytic reduction in the presence of excess diborane. Related reactions of 4 and 5 with CS2 provided insertion products 10, {[(PNNPFlu)Cu2]2[μ-S2C(Bcat)2]}[NTf2]2, and 11, [(PNNPFlu)Cu2(μ,κ2-S2CBpin)][NTf2], respectively. These products feature Cu-S-C-B linkages analogous to those of proposed CO2 insertion intermediate
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