Search for non-Gaussianity in pixel, harmonic and wavelet space: compared and combined

We present a comparison between three approaches to test non-Gaussianity of cosmic microwave background data. The Minkowski functionals, the empirical process method and the skewness of wavelet coefficients are applied to maps generated from non-standard inflationary models and to Gaussian maps with point sources included. We discuss the different power of the pixel, harmonic and wavelet space methods on these simulated almost full-sky data (with Planck like noise). We also suggest a new procedure consisting of a combination of statistics in pixel, harmonic and wavelet space.Comment: Accepted for publication in PR

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Pyridazin-3(2H)-ones via D2-isoxazoline intermediates: synthetic studies

An efficient method for the prepn. of 6-​substituted-​4,​5-​dihydro-​3(2H)​pyridazinones I (R = alkyl, benzyl, etc.) was described. The synthetic strategy is based on Δ2-​isoxazolines chem. which were unmasked by N-​O bond cleavage and cyclized to the target compd. Utilizing the same approach was possible to obtain both 6-​substituted-​3(2H)​-​pyridazinones and 6-​substituted-​4-​hydroxy-​4,​5-​dihydro-​3(2H)​-​pyridazinones. This protocol was also extended to a C-​nucleoside starting from β-​ribofuranosylnitromethane. Moreover, an intramol. version of this methodol. has been developed to prep. a known antiulcer tricyclic 3(2H)​-​pyridazinone. The unusual transformation of compds. I into the corresponding 3-​(1-​naphthyl)​propionic acid Et ester derivs. was also reported

Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone analogs of pyrrolo[1,4]benzodiazepines (PBDs)

A new class of pyrrolo[1,​4]​benzodiazepines (PBDs) analogs featuring a pyrazolo[4,​3-​e]​pyrrolo[1,​2-​a]​[1,​4]​diazepinone ring system has been designed and synthesized. In these compds. the A-​benzene ring, characteristic of PBDs, has been replaced by a dimethylpyrazole ring, a modification suggested by modeling studies performed on the PBD base structure. Biol. evaluation revealed appreciable antitumor activity for I and II (8.84-​22.4 μM) which encourages further investigation of the N6 or N7 alkyl pyrazole analogs