The one-loop and Sommerfeld electroweak corrections to the Wino dark matter annihilation

We compute the present-day Wino dark matter annihilation cross-section including the one-loop radiative corrections together with the fully treated electroweak Sommerfeld effect. We discuss what is the consistent way of incorporating these two corrections simultaneously and why simply using the running coupling constants values at the Wino mass scale is not correct. The results show that up to a few TeV scale the full one-loop computation makes the cross-section smaller up to about 30% with respect to the Sommerfeld enhanced tree level result and are considerably larger than the tree or one-loop level without the Sommerfeld effect.Comment: 25 pages, 13 figures; clarifications on the range of validity of the results, in particular for the annihilation into neutral gauge bosons; attached tabulated results for the cross-section

Antiferromagnetic spintronics

Antiferromagnetic materials are magnetic inside, however, the direction of their ordered microscopic moments alternates between individual atomic sites. The resulting zero net magnetic moment makes magnetism in antiferromagnets invisible on the outside. It also implies that if information was stored in antiferromagnetic moments it would be insensitive to disturbing external magnetic fields, and the antiferromagnetic element would not affect magnetically its neighbors no matter how densely the elements were arranged in a device. The intrinsic high frequencies of antiferromagnetic dynamics represent another property that makes antiferromagnets distinct from ferromagnets. The outstanding question is how to efficiently manipulate and detect the magnetic state of an antiferromagnet. In this article we give an overview of recent works addressing this question. We also review studies looking at merits of antiferromagnetic spintronics from a more general perspective of spin-ransport, magnetization dynamics, and materials research, and give a brief outlook of future research and applications of antiferromagnetic spintronics.Comment: 13 pages, 7 figure

Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study

INTRODUCTION: Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, we examined the association between common genetic variation in this pathway and mammographic density. METHODS: We conducted a cross-sectional analysis among controls (n = 1,121) who were between the ages of 42 and 78 years at mammography, from a breast cancer case-control study nested within the Nurses' Health Study cohort. At the time of mammography, 204 women were premenopausal and 917 were postmenopausal. We genotyped 29 haplotype-tagging SNPs demonstrated to capture common genetic variation in IGF1, IGF binding protein (IGFBP)-1, and IGFBP-3. RESULTS: Common haplotype patterns in three of the four haplotype blocks spanning the gene encoding IGF1 were associated with mammographic density. Haplotype patterns in block 1 (p = 0.03), block 3 (p = 0.009), and block 4 (p = 0.007) were associated with mammographic density, whereas those in block 2 were not. None of the common haplotypes in the three haplotype blocks spanning the genes encoding IGFBP-1/IGFBP-3 were significantly associated with mammographic density. Two haplotype-tagging SNPs in IGF1, rs1520220 and rs2946834, showed a strong association with mammographic density. Those with the homozygous variant genotype for rs1520220 had a mean percentage mammographic density of 19.6% compared with those with the homozygous wild-type genotype, who had a mean percentage mammographic density of 27.9% (p for trend < 0.0001). Those that were homozygous variant for rs2946834 had a mean percentage mammographic density of 23.2% compared with those who were homozygous wild-type with a mean percentage mammographic density of 28.2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005). CONCLUSION: Common genetic variation in IGF1 is strongly associated with percentage mammographic density

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer

Rationale, design and population baseline characteristics of the PERFORM Vascular Project: an ancillary study of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) trial

&lt;p&gt;&lt;b&gt;Purpose&lt;/b&gt;&lt;/p&gt; &lt;p&gt;PERFORM is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke or transient ischemic attacks (TIAs). The PERFORM Vascular Project will evaluate the effect of terutroban on progression of atherosclerosis, as assessed by change in carotid intima-media thickness (CIMT) in a subgroup of patients.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and results&lt;/b&gt;&lt;/p&gt; &lt;p&gt;The Vascular Project includes structural (CIMT, carotid plaques) and functional (carotid stiffness) vascular studies in all patients showing at least one carotid plaque at entry. Expected mean follow-up is 36 months. Primary endpoint is rate of change of CIMT. Secondary endpoints include emergent plaques and assessment of carotid stiffness. 1,100 patients are required for 90% statistical power to detect treatment-related CIMT difference of 0.025 mm. The first patient was randomized in April 2006.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt;&lt;/p&gt; &lt;p&gt;The PERFORM Vascular Project will investigate terutroban’s effect on vascular structure and function in patients with a history of ischemic stroke or TIAs.&lt;/p&gt

Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

<p>Abstract</p> <p>Background</p> <p>Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.</p> <p>Methods</p> <p>Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3).</p> <p>Results</p> <p>The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis.</p> <p>Conclusion</p> <p>Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.</p