Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior parent are pooled, the DNA extracted and sequenced. Genomic regions linked to the trait of interest are identified by searching the pool for overrepresented alleles that normally originate from the superior parent. BSA data analysis is non-trivial due to sequencing, alignment and screening errors. Results: To increase the power of the BSA technology and obtain a better distinction between spuriously and truly linked regions, we developed EXPLoRA (EXtraction of over-rePresented aLleles in BSA), an algorithm for BSA data analysis that explicitly models the dependency between neighboring marker sites by exploiting the properties of linkage disequilibrium through a Hidden Markov Model (HMM). Reanalyzing a BSA dataset for high ethanol tolerance in yeast allowed reliably identifying QTLs linked to this phenotype that could not be identified with statistical significance in the original study. Experimental validation of one of the least pronounced linked regions, by identifying its causative gene VPS70, confirmed the potential of our method. Conclusions: EXPLoRA has a performance at least as good as the state-of-the-art and it is robust even at low signal to noise ratio's i.e. when the true linkage signal is diluted by sampling, screening errors or when few segregants are available

Anomaly detection by X-ray tomography and probabilistic fatigue assessment of aluminum brackets manufactured by PBF-LB

The assessment of safety-critical components for fatigue applications is a key requirement for metal additive manufacturing (AM) applications. Material anomalies play a relevant role in determining the fatigue resistance properties of a component. X-ray computed tomography (CT) helps collect important information on these flaws, such as their size and position within a part. In this study, we discuss how to employ anomaly data detected on an AlSi10Mg bracket manufactured by laser- powder bed fusion to describe the prospective allowable life of a component under a given operating condition. A statistical analysis was conducted on the specimens and component to derive the correlation between different resolution scans and analyze the uncertainties of the micro-CT measurements. The full-scale non-destructive evaluation (NDE) can be constrained to large voxel sizes. Eventually, the authors proposed a fully probabilistic route for assessment instead of a simple deterministic assessment based on safety factors. This assessment enables designers to consider the uncertainties of the assessment (uncertainties of micro-CT detection and the model for fatigue strength)

Full Crystallographic Imaging of Hexagonal Boron Nitride Monolayers with Phonon-Enhanced Sum-Frequency Microscopy

Hexagonal boron nitride (hBN) is an important 2D material for van der Waals heterostructures, single photon emitters, and infrared nanophotonics. The optical characterization of mono- and few-layer samples of hBN however remains a challenge as the material is almost invisible optically. Here we introduce phase-resolved sum-frequency microscopy as a technique for imaging monolayers of hBN grown by chemical vapor deposition (CVD) and visualize their crystal orientation. A combination of femtosecond mid-infrared (IR) and visible laser pulses is used for sum-frequency generation (SFG), which is imaged in a wide-field optical microscope. The IR laser resonantly excites a phonon of hBN that leads to an ~800-fold enhancement of the SFG intensity, making it possible to image large 100x100 µm2 sample areas in less than 1 s. Implementing heterodyne detection in combination with azimuthal rotation of the sample further provides full crystallographic information. Through combined knowledge of topography and crystal orientation, we find that triangular domains of CVD-grown monolayer hBN have nitrogen-terminated zigzag edges. Overall, SFG microscopy can be used as an ultra-sensitive tool to image crystal structure, strain, stacking sequences, and twist angles, and is applicable to the wide range of van der Waals structures, where location and identification of monolayer regions and interfaces with broken inversion symmetry is of paramount importance

Building a Web-Based Knowledge Repository on Climate Change to Support Environmental Communities

This paper presents the technology base and roadmap of the Climate Change Collaboratory, a Web-based platform that aims to strengthen the relations between scientists, educators, environmental NGOs, policy makers, news media and corporations - stakeholders who recognize the need for adaptation and mitigation, but differ in world-views, goals and agendas. The collaboratory manages expert knowledge and provides a platform for effective communication and collaboration. It aims to assist networking with leading international organizations, bridges the science-policy gap and promotes rich, self-sustaining community interaction to translate knowledge into coordinated action. Innovative survey instruments in the tradition of "games with a purpose" will create shared meaning through collaborative ontology building and leverage social networking platforms to capture indicators of environmental attitudes, lifestyles and behaviors

Current views on the role of Notch signaling and the pathogenesis of human leukemia

The Notch signaling pathway is highly conserved from Drosophila to humans and plays an important role in the regulation of cellular proliferation, differentiation and apoptosis

Clinical outcomes of pediatric kidney replacement therapy after childhood cancer—An ESPN/ERA Registry study

Cancer and its treatment may lead to kidney injury and the need for kidney replacement therapy (KRT). We identified 287 pediatric KRT patients with a history of malignancy from the European Society for Paediatric Nephrology/European Renal Association Registry. Of these, 197 had cancer as a primary cause of KRT (group 1) and 90 had a malignancy diagnosis before KRT (group 2). Two matched controls without malignancy were randomly selected for each patient. Data were complemented with a questionnaire. Median time to kidney transplantation (KT) from KRT initiation was 2.4 (IQR: 1.5-4.7), 1.5 (IQR: 0.4-3.3), 3.6 (IQR: 1.3 to Q3 not reached), and 1.1 (IQR: 0.3-3.6) years for group 1, their controls, group 2, and their controls, respectively. Overall 10-year mortality for those on KRT was higher among cancer patients vs controls in group 1: 16% vs 9% (adjusted hazard ratio 2.02, 95% CI: 1.21-3.37) and in group 2: 23% vs 14% (adjusted hazard ratio 2.32, 95% CI: 1.11-4.85). In contrast, 10-year patient survival after the first KT was comparable to controls (93% vs 96%; 100% vs 94%, in groups 1 and 2, respectively). In summary, childhood cancer survivors’ KT was delayed, and their overall mortality when on KRT was increased, but once transplanted, their long-term outcome was similar to other KT recipients

Reproducibility of electromagnetic field simulations of local radiofrequency transmit elements tailored for 7 T MRI

The literature reports on radiofrequency (RF) transmit (Tx) elements tailored for ultrahigh-field (UHF) magnetic resonance imaging (MRI) showed confounded reproducibility due to variations in simulation tools, modeling assumptions, and meshing techniques. This study proposes a standardized methodology to improve reproducibility and consistency across research sites (testers) and simulation tools (testing conditions). The methodology includes detailed simulation workflow and performance metrics for RF Tx elements. The impact of the used mesh setting is assessed. Following the methodology, a reproducibility study was conducted using CST Microwave Studio Suite, HFSS, and Sim4Life. The methodology and simulations were ultimately validated through 7 T MRI phantom experiments. The reproducibility study showed consistent performance with less than 6% standard deviation for B(1)(+) fields and 12% for peak SAR averaged over 10 g tissue (pSAR10g). The SAR efficiency metric (|B(1)(+)|/√pSAR(10g)) was particularly robust (<5%). The simulated and experimental |B(1)(+)| maps showed good qualitative agreement. This study demonstrates the feasibility of a standardized methodology for achieving reproducible RF Tx element electromagnetic field simulations. By following the FAIR principles including making the framework publicly available, we promote transparency and collaboration within the MRI community, supporting the advancement of technological innovation and improving patient safety in UHF-MRI

Loss of NOTCH2 Positively Predicts Survival in Subgroups of Human Glial Brain Tumors

The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH) on chromosome 1p is associated with the longer survival of oligodendroglioma (OD) patients. To test the clinical relevance of 1p loss in glioblastomas (GBM) patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0.0175), while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918). Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test) allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925) that is equivalent to histological classification combined with the D1S2696 status (0.954) and higher than current genetic evaluation by 1p/19q LOH (0.762). Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas