Geothermal Potential of the Brenner Base Tunnel—Initial Evaluations

Increasing demands on mobility and transport, but limited space above ground, lead to new traffic routes being built, even more underground in the form of tunnels. In addition to improving the traffic situation, tunnels offer the possibility of contributing to climate-friendly heating by indirectly serving as geothermal power plants. In this study, the geothermal potential of the future longest railway tunnel in the world, the Brenner Base Tunnel, was evaluated. At the Brenner Base Tunnel, warm water naturally flows from the apex of the tunnel towards the city of Innsbruck, Austria. In order to estimate its geothermal potential, hydrological data of discharge rates and temperatures were investigated and analyzed. The investigations indicated the highest geothermal potential in the summertime, while the lowest occurs during winter. It could be shown that these variations were a result of cooling during discharge through areas of low overburden (mid mountain range), where the tunnel atmosphere is increasingly influenced by the air temperatures outside the tunnel. Nevertheless, the calculations showed that there will be a usable potential after completion of the tunnel

Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods

Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Cytoplasmic fused in sarcoma (FUS) aggregates are pathological hallmarks of FUS-ALS. Proper shuttling between the nucleus and cytoplasm is essential for physiological cell function. However, the initial event in the pathophysiology of FUS-ALS remains enigmatic. Using human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs), we show that impairment of poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response (DDR) signaling due to mutations in the FUS nuclear localization sequence (NLS) induces additional cytoplasmic FUS mislocalization which in turn results in neurodegeneration and FUS aggregate formation. Our work suggests that a key pathophysiologic event in ALS is upstream of aggregate formation. Targeting DDR signaling could lead to novel therapeutic routes for ameliorating ALS

African Head and Neck Society Clinical Practice guidelines for thyroid nodules and cancer in developing countries and limited resource settings

Background International thyroid nodule and cancer management guidelines generally fail to take into account potential limitations in diagnostic and treatment resources. Methods Thyroid cancer specialists from the African Head and Neck Society and American Head & Neck Society Endocrine Section developed guidelines for diagnosis and management of thyroid nodules and cancer in low resource settings. Recommendations were based on literature review and expert opinion, with level of evidence defined. Results Using the ADAPTE process, diagnostic and treatment algorithms were adapted from the National Comprehensive Cancer Network (NCCN). Low resource settings were simulated by systematically removing elements such as availability of laboratory testing, hormone replacement, imaging, and cytopathology from NCCN guidelines. Conclusions Successful management of thyroid nodules and cancer in low resource settings requires adaptation of treatment methodologies. These guidelines define specific scenarios where either more or less aggressive intervention for thyroid pathology may be advisable based on limited available resources

Robots in machining

Robotic machining centers offer diverse advantages: large operation reach with large reorientation capability, and a low cost, to name a few. Many challenges have slowed down the adoption or sometimes inhibited the use of robots for machining tasks. This paper deals with the current usage and status of robots in machining, as well as the necessary modelling and identification for enabling optimization, process planning and process control. Recent research addressing deburring, milling, incremental forming, polishing or thin wall machining is presented. We discuss various processes in which robots need to deal with significant process forces while fulfilling their machining task

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Life Cycle Assessment of High-Performance Railway Infrastructure, Analysis of Superstructures in Tunnels and on Open Tracks

Almost 25% of the environmental pollution, measured by the indicator of global greenhouse emissions, is emitted by transport. Changes in the mobility behavior of the population will be essential if the 17 UN Sustainable Development Goals (SDGs) and the goals of the EU Commission’s Green Deal are to be attained. Accordingly, the existing infrastructure has to transform into a sustainable transport infrastructure through further optimizations in the future. Therefore, continuous optimizations and improvements of designs, materials, and processes are crucial to achieving long-term sustainability. This study investigates different superstructures with the method of life cycle assessment using the example of the emerging high-performance infrastructure at the Brenner Base Tunnel (BBT). The study analyzes all relevant life cycle stages (A1–C4) and validates different effects of service lifetimes of superstructure elements on the open track and in the tunnel. The results, which are presented in the form of GWP, AP, and NRCED, show that there is environmental reduction potential, especially in the stage of use. As more frequent modernization cycles and the associated remanufacturing of superstructure elements account for a significant proportion of the total environmental impact, lifetime extending optimization of products yields improvements in the ecological footprint

Lipid droplets at a glance

Lipid droplets (LDs) are the major cellular organelles for the storage of neutral lipids. Excessive lipid storage in LDs is central to the pathogenesis of prevalent metabolic diseases, such as obesity, diabetes and atherosclerosis; LDs are, therefore, crucial in the development of these diseases. Long considered to be inert, LDs have recently attracted great interest as dynamic structures at the hub of lipid and energy metabolism. Major findings that highlight the diversity and dynamics of LDs include the identification of key proteins that are involved in LD biology, the discovery o

Laser scored machining of fiber reinforced plastics to prevent delamination

Delamination is a major problem in contour milling of fiber reinforced plastics (FRP) causing scrap or rework. Today, delamination avoidance limits overall productivity and tool life. Damage of the top layer of a composite structure is initiated if fibers are not cut during first engagement of the cutting edge, but deflected. Generated cracks propagate due to recurrent contact of fibers with the rotating tool. In contrast, when laser cutting FRP, the heat input often leads to an extensive heat-affected zone (HAZ), particularly in case of large laminate thickness and high energy input. Combination of both processes is a promising approach to overcome the mentioned disadvantages. Experiments indicate that pre-scoring of the top layer is possible with negligible HAZ for FRP materials using proper laser parameters, especially low energy input per unit length. Positioning of the laser scored kerf along the contour to be manufactured by the subsequent milling tool prevents crack propagation along the fiber direction even with a heavily worn milling tool at increased feed rate. Furthermore, laser pre-scoring eliminates protruding fibers and allows for edge chamfering. The process understanding is enhanced using simulation of the laser pre-scoring, particularly considering heat conduction and forced convection, as well as by presenting a model for the mechanism of delamination prevention.The project on which this paper is based is funded by the German Federal Ministry of Economics Affairs and Energy under funding code 20W1509C