Large oxygen-isotope effect in Sr_{0.4}K_{0.6}BiO_{3}: Evidence for phonon-mediated superconductivity

Oxygen-isotope effect has been investigated in a recently discovered superconductor Sr_{0.4}K_{0.6}BiO_{3}. This compound has a distorted perovskite structure and becomes superconducting at about 12 K. Upon replacing ^{16}O with ^{18}O by 60-80%, the T_c of the sample is shifted down by 0.32-0.50 K, corresponding to an isotope exponent of alpha_{O} = 0.40(5). This isotope exponent is very close to that for a similar bismuthate superconductor Ba_{1-x}K_{x}BiO_{3} with T_c = 30 K. The very distinctive doping and T_c dependencies of alpha_{O} observed in bismuthates and cuprates suggest that bismuthates should belong to conventional phonon-mediated superconductors while cuprates might be unconventional supercondutors.Comment: 9 pages, 5 figure

The Fueling and Evolution of AGN: Internal and External Triggers

In this chapter, I review the fueling and evolution of active galactic nuclei (AGN) under the influence of internal and external triggers, namely intrinsic properties of host galaxies (morphological or Hubble type, color, presence of bars and other non-axisymmetric features, etc) and external factors such as environment and interactions. The most daunting challenge in fueling AGN is arguably the angular momentum problem as even matter located at a radius of a few hundred pc must lose more than 99.99 % of its specific angular momentum before it is fit for consumption by a BH. I review mass accretion rates, angular momentum requirements, the effectiveness of different fueling mechanisms, and the growth and mass density of black BHs at different epochs. I discuss connections between the nuclear and larger-scale properties of AGN, both locally and at intermediate redshifts, outlining some recent results from the GEMS and GOODS HST surveys.Comment: Invited Review Chapter to appear in LNP Volume on "AGN Physics on All Scales", Chapter 6, in press. 40 pages, 12 figures. Typo in Eq 5 correcte

Gene-centric functional dissection of human genetic variation uncovers regulators of hematopoiesis

Genome-wide association studies (GWAS) have identified thousands of variants associated with human diseases and traits. However, the majority of GWAS-implicated variants are in non-coding regions of the genome and require in depth follow-up to identify target genes and decipher biological mechanisms. Here, rather than focusing on causal variants, we have undertaken a pooled loss-of-function screen in primary hematopoietic cells to interrogate 389 candidate genes contained in 75 loci associated with red blood cell traits. Using this approach, we identify 77 genes at 38 GWAS loci, with most loci harboring 1-2 candidate genes. Importantly, the hit set was strongly enriched for genes validated through orthogonal genetic approaches. Genes identified by this approach are enriched in specific and relevant biological pathways, allowing regulators of human erythropoiesis and modifiers of blood diseases to be defined. More generally, this functional screen provides a paradigm for gene-centric follow up of GWAS for a variety of human diseases and traits

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P = 0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P = 0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P = 0.08) and del(5q) (P = 0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progressionfree survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P = 0.05). These findings comprise the largest MDS R72P SNP analysis