Atomic data from the IRON project - LI. Electron impact excitation of FeIX

We calculate collision strengths and thermally averaged collision strengths for electron excitation between the one hundred and forty energetically lowest levels of Fe8+. The scattering target is more elaborate than in any earlier work and large increases are found in the excitation rates among the levels of the 3s(2)3p(5)3d electron configuration due to resonance series that have not been considered previously. The implications for solar and stellar spectroscopy have been discussed elsewhere (Storey & Zeippen 2001). We correct some errors that were made in generating the figures given in that paper and present corrected versions

Atom gravimeters and gravitational redshift

In a recent paper, H. Mueller, A. Peters and S. Chu [A precision measurement of the gravitational redshift by the interference of matter waves, Nature 463, 926-929 (2010)] argued that atom interferometry experiments published a decade ago did in fact measure the gravitational redshift on the quantum clock operating at the very high Compton frequency associated with the rest mass of the Caesium atom. In the present Communication we show that this interpretation is incorrect.Comment: 2 pages, Brief Communication appeared in Nature (2 September 2010

Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies

To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level

Taming non-radiative recombination in Si nanocrystals interlinked in a porous network

A range of the distinctive physical properties, comprising high surface-to-volume ratio, possibility to achieve mechanical and chemical stability after a tailored treatment, controlled quantum confinement and the room-temperature photoluminescence, combined with mass production capabilities offer porous silicon unmatched capabilities required for the development of electro-optical devices. Yet, the mechanism of the charge carrier dynamics remains poorly controlled and understood. In particular, non-radiative recombination, often the main process of the excited carrier's decay, has not been adequately comprehended to this day. Here we show, that the recombination mechanism critically depends on the composition of surface passivation. That is, hydrogen passivated material exhibits Shockley–Read–Hall type of decay, while for oxidised surfaces, it proceeds by two orders of magnitude faster and exclusively through the Auger process. Moreover, it is possible to control the source of recombination in the same sample by applying a cyclic sequence of hydrogenation–oxidation–hydrogenation processes, and, consequently switching on-demand between Shockley–Read–Hall and Auger recombinations. Remarkably, irregardless of the recombination mechanism, the rate constant scales inversely with the average volume of individual silicon nanocrystals contained in the material. Thus, the type of the non-radiative recombination is established by the composition of the passivation, while its rate depends on the degree of the charge carriers’ quantum confinement

Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Multiple Oncogenic Pathway Signatures Show Coordinate Expression Patterns in Human Prostate Tumors

BACKGROUND: Gene transcription patterns associated with activation of oncogenes Myc, c-Src, beta-catenin, E2F3, H-Ras, HER2, EGFR, MEK, Raf, MAPK, Akt, and cyclin D1, as well as of the cell cycle and of androgen signaling have been generated in previous studies using experimental models. It was not clear whether genes in these "oncogenic signatures" would show coordinate expression patterns in human prostate tumors, particularly as most of the signatures were derived from cell types other than prostate. PRINCIPAL FINDINGS: The above oncogenic pathway signatures were examined in four different gene expression profile datasets of human prostate tumors (representing approximately 250 patients in all), using both Q1-Q2 and one-sided Fisher's exact enrichment analysis methods. A significant fraction (approximately 5%) of genes up-regulated experimentally by Myc, c-Src, HER2, Akt, or androgen were co-expressed in human tumors with the oncogene or biomarker corresponding to the pathway signature. Genes down-regulated experimentally, however, did not show anticipated patterns of anti-enrichment in the human tumors. CONCLUSIONS: Significant subsets of the genes in these experimentally-derived oncogenic signatures are relevant to the study of human prostate cancer. Both molecular biologists and clinical researchers could focus attention on the relatively small number of genes identified here as having coordinate patterns that arise from both the experimental system and the human disease system

Chameleon radiation by oceanic dispersal

Historical biogeography is dominated by vicariance methods that search for a congruent pattern of fragmentation of ancestral distributions produced by shared Earth history(1-3). A focus of vicariant studies has been austral area relationships and the break-up of the supercontinent Gondwana(3-5). Chameleons are one of the few extant terrestrial vertebrates thought to have biogeographic patterns that are congruent with the Gondwanan break-up of Madagascar and Africa(6,7). Here we show, using molecular and morphological evidence for 52 chameleon taxa, support for a phylogeny and area cladogram that does not fit a simple vicariant history. Oceanic dispersal-not Gondwanan breakup-facilitated species radiation, and the most parsimonious biogeographic hypothesis supports a Madagascan origin for chameleons, with multiple 'out-of-Madagascar' dispersal events to Africa, the Seychelles, the Comoros archipelago, and possibly Reunion Island. Although dispersal is evident in other Indian Ocean terrestrial animal groups(8-16), our study finds substantial out-of-Madagascar species radiation, and further highlights the importance of oceanic dispersal as a potential precursor for speciation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62614/1/415784a.pd

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe