Evaluation of turbulent dissipation rate retrievals from Doppler Cloud Radar

Turbulent dissipation rate retrievals from cloud radar Doppler velocity measurements are evaluated using independent, in situ observations in Arctic stratocumulus clouds. In situ validation data sets of dissipation rate are derived using sonic anemometer measurements from a tethered balloon and high frequency pressure variation observations from a research aircraft, both flown in proximity to stationary, ground-based radars. Modest biases are found among the data sets in particularly low- or high-turbulence regimes, but in general the radar-retrieved values correspond well with the in situ measurements. Root mean square differences are typically a factor of 4-6 relative to any given magnitude of dissipation rate. These differences are no larger than those found when comparing dissipation rates computed from tetheredballoon and meteorological tower-mounted sonic anemometer measurements made at spatial distances of a few hundred meters. Temporal lag analyses suggest that approximately half of the observed differences are due to spatial sampling considerations, such that the anticipated radar-based retrieval uncertainty is on the order of a factor of 2-3. Moreover, radar retrievals are clearly able to capture the vertical dissipation rate structure observed by the in situ sensors, while offering substantially more information on the time variability of turbulence profiles. Together these evaluations indicate that radar-based retrievals can, at a minimum, be used to determine the vertical structure of turbulence in Arctic stratocumulus clouds

A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

This work was partially supported by the CENIT program from the Centro Tecnológico Industrial (CEN-20091016), grants from the Spanish Institute of Health Carlos III (ADE10/00026, PI09/02444, PI12/00511, Acción Transversal de Cáncer) grants from the Fondo de Investigacion Sanitaria/FEDER (08/1276, 08/0024, PS09/02368, 11/00219, 11/00681), and by COST office through COST action BM1206. SCB is supported by contracts from the Fondo de Investigación Sanitaria (CP 03-0070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Centro Tecnológico IndustrialInstituto de Salud Carlos IIIFondo de Investigación Sanitaria / FEDE

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background\ud In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.\ud \ud Methods\ud We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings.\ud \ud Results\ud Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls).\ud \ud Conclusions\ud Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10-6 were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10 -7 in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10 -9). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation

Background rejection in NEXT using deep neural networks

[EN] We investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the use of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain and FEDER under grants CONSOLIDER-Ingenio 2010 CSD2008-0037 (CUP), FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; GVA under grant PROMETEO/2016/120. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the United States Department of Energy. JR acknowledges support from a Fulbright Junior Research Award.Renner, J.; Farbin, A.; Muñoz Vidal, J.; Benlloch-Rodríguez, J.; Botas, A.; Ferrario, P.; Gómez-Cadenas, J.... (2017). Background rejection in NEXT using deep neural networks. Journal of Instrumentation. 12. https://doi.org/10.1088/1748-0221/12/01/T01004S1

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted