AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Fourier transform of percol gradients boosts CNN classification ofhereditary hemolytic anemias.

Hereditary hemolytic anemias are genetic disorders that af-fect the shape and density of red blood cells. Genetic testscurrently used to diagnose such anemias are expensive andunavailable in the majority of clinical labs. Here, we pro-pose a method for identifying hereditary hemolytic anemiasbased on a standard biochemistry method, called Percollgradient, obtained by centrifuging a patient’s blood. Our hy-brid approach consists on using spatial data-driven features,extracted with a convolutional neural network and spectralhandcrafted features obtained from fast Fourier transform.We compare late and early feature fusion with AlexNet andVGG16 architectures. AlexNet with late fusion of spectralfeatures performs better compared to other approaches. Weachieved an average F1-score of 88% on different classes sug-gesting the possibility of diagnosing of hereditary hemolyticanemias from Percoll gradients. Finally, we utilize Grad-CAM to explore the spatial features used for classification

Correlation between suprathermal electron bursts, broadband extremely low frequency waves, and local ion heating in the midaltitude cleft//low-latitude boundary layer observed by Cluster

The Cluster spacecraft often cross the midaltitude cleft/cusp and observe a very well defined “electron-only cleft” region consisting of electron injections without magnetosheath ions. This region contains soft suprathermal (<500 eV) electron bursts in antifield and/or field-aligned directions. We present an example of such observations which shows that the O+ ion outflow at midaltitudes appears just poleward of the open-closed boundary simultaneously with electron injections and was observed in the cleft, cusp, and mantle in the form of narrow energy beam. Inside the “electron-only” cleft the suprathermal electron bursts are strongly correlated with strong O+ and H+ ion heating and with localized extra low frequency (ELF) (1–10 Hz) magnetic field wave power with broadband spectra. Our study shows that strong ion heating was observed only in the region with electron field-aligned anisotropy more than 2. In addition, comparison of particle data from two spacecraft, which crossed the heating region with a time difference of 4 min, shows the correlation between ion outflow fluxes and fluxes of the injected electrons. Whereas ELF electromagnetic waves are localized inside the ion heating region, ELF electrostatic waves are detected throughout the cleft/cusp/mantle regions, where strong ion heating was not observed, suggesting that electromagnetic ELF waves heat ions in the cleft region. Owing to the absence of magnetosheath ions and strong field-aligned currents, we suppose that inside “electron-only” cleft region the suprathermal electron bursts are most likely an energy source for the wave destabilization. We suggest that the location of the heating region and the level of the outflow ion fluxes could be related to electron injection in the cleft in such events