Theoretical Studies of Several Small-Ring Precursors to (+)-JQ1

We present the results of DFT(B3LYP) calculations on several precursors to (+)-JQ1 using an accurate basis set, including a report of conformational analysis, thermochemistry, optimized geometries and electrostatic potentials, and calculated IR and Raman spectra. Species include (I)1H-1,4-diazepin-2(3H)-imine, (II) 9H-[1,2,4]triazolo[4,3-a][1,4]diazepine, (III) 6H-thieno[3,2-f][1,2,4]triazolo[4,3a][1,4]diazepine, and (IV) 4-(4-chlorophenyl)-6H-thieno[3,2f][1,2,4]triazolo[4,3-a][1,4]diazepine. Studies are also reported on monobrominated (II)-(IV) substituted at the chiral center of the seven member ring, including a comparison of the energetics of equatorial versus axial bromination of the parent precursor. Implications with regard to the larger structure of (+)-JQ1 are discussed

Screening the genome to detect an association with hypertension

We report tree-based association analysis as applied to the two Framingham cohorts and to the first replication of the simulated data obtained from the Genetic Analysis Workshop 13. For this analysis, familial association is ignored. The two endpoints examined are hypertension status at initial visit and time-to-hypertension, using a censored data approach. Although linkage association has previously been reported with hypertension, we found no association using the tree-based methodology

Bone Density Following Three Years of Recovery from Long-Duration Space Flight

It is well recognized that bone mineral density [BMD] at load-bearing sites of the hip and spine sustain significant loss during space flight, estimated at approximately 0.5-1.0% per month. However, the long-term effects on bone health following return from long-duration space flight remain unclear. It is unknown whether BMD for men recovers beyond 1 year following return from space to what would be predicted or if deficits persist. Using our previously created prediction models, we compared the observed BMD of male US crew following 3 years since returning from longduration space flight with what would be predicted if they had not been exposed to microgravity

Does Short Duration Space Flight have a Negative Effect on Bone Density?

No abstract availabl

Comparison of variable and model selection methods for genetic association studies using the GAW15 simulated data

We compared and evaluated several variable and model selection methods using Bayesian and non-Bayesian approaches for three replicates of the Genetic Analysis Workshop 15 (GAW15) simulated data. In doing so, two phenotypes were utilized: rheumatoid arthritis (RA) affection status as a binary trait and IgM as a continuous measure. The analyses were performed adjusting for sex, age, and smoking status. For both outcomes, all the methods were comparable in finding the single-nucleotide polymorphisms (SNPs) generated to have a genetic signal. We successfully identified the susceptibility SNPs for RA in the HLA region (chromosome 6), and chromosome 18, and the susceptibility SNP for IgM on chromosome 11; however, many of the methods produced false-positive results

Bone Density Following Long Duration Space Flight and Recovery

At approx.12 months, Bone Mineral Density (BMD) at most sites in men remained lower than would be predicted, raising concerns for long-term bone health consequences following space flight. Additional analyses based on longer follow-up are being conducted. Although the N is too small for definitive conclusions, women had lower rates of loss at load-bearing sites of the hip and spine immediately post-flight relative to men and smaller differences between observed vs. predicted BMD at most sites, both immediately and 12 months post-flight, relative to men. The role of other exposures/risk factors need to be explored to further understand these possible gender differences in BMD loss and recovery following long-duration space flight

Reply to : On powerful GWAS in admixed populations

Non peer reviewe