Geometric deep learning: Ein Überblick

In dem sich in rapidem Tempo entwickelnden Gebiet des maschinellen Lernens mittels künstlicher neuronaler Netzwerke werden Jahr für Jahr bahnbrechende Erfolge erzielt. Dies gilt insbesondere im Fall euklidischer Daten wie Bildsignale oder sequentielle Daten, beispielsweise Text in natürlicher Sprache, Audiosignale, Zeitreihendaten oder Genomsequenzen. Die Verarbeitung nichteuklidischer geometrischer Datenstrukturen wie Graphen, Mannigfaltigkeiten, Polygonnetze oder Punktwolken hingegen ist weniger erforscht. Da eine Vielzahl von Problemstellungen sich mittels Graphen beschreiben lässt, eröffnen die Methoden des aufsteigenden Teilgebiets namens geometric deep learning nicht nur für die Computergrafik und das maschinelle Sehen ungeahnte Möglichkeiten. Aufgabe dieser Arbeit ist es, einen umfassenden Überblick über diese junge Teildisziplin und ihre Techniken zu verschaffen. Ziel dabei ist es, auch unerfahrenen Lesern einen zugänglichen Einstieg in diesen Themenbereich zu präsentieren. Zu diesem Zweck werden unterschiedliche Ansätze zur Verallgemeinerung der klassischen Faltung auf nichteuklidische Gebiete behandelt. Darüber hinaus werden am Beispiel verschiedener Anwendungsfälle konkrete neuronale Netzwerkmodelle vorgestellt

Are a “can do” Attitude and a can of Red Bull Enough? Workload and Fatigue in High-stakes, High-demand Carrier Sortie Operations

AbstractThe purpose of this investigation was to examine the role of fatigue and crew endurance in human performance of Carrier Sortie requirements; this mission capability involves high-stakes, high-demand, high-tempo operations in a challenging maritime environment. The researchers engaged with a panel of Nimitz crewmembers for a discussion of workload, notional schedules, and endurance risk factors. Workload was examined with models that consider the human capacity for sustaining. The investigation found that more attention is paid to physical fatigue, compared to cognitive or mental fatigue. Crewmembers emphasized that crew has a “can do” attitude to combat fatigue; the crew stated that “pride and adrenaline overpower fatigue…plus coffee and Red Bull.” They indicated that this results in good initiative, but at times bad judgment while trying to accomplish the work. The current research posits that fatigue is likely to reduce the ability of crewmembers to tolerate sustained performance and associated increased physiological and cognitive costs. However, the authors also recognize the limits of fatigue science with regard to predicting human capacity in intense operational and combat conditions. There is much anecdotal information to suggest that sailors are managing fatigue despite the predictions of various fatigue models. As a result, we cannot yet predict with certainty when the accumulated workload and fatigue of the individual sailor will be untenable, or identify critical thresholds of degraded cognitive capacity and decision making. Rather than rely solely on fatigue prediction software, it is recommended that potential mitigations are considered that might provide the crew more tools to manage endurance as a fatigue abatement strategy. The development of a crew endurance program to mitigate the risks posed by fatigue and reduced alertness during carrier sortie operations would identify risks relating to fatigue and alertness, and generate solutions to mitigate these risks by controlling exposure to endurance risk factors during normal operations so that the crew will be better prepared to respond to any operational demand

Modulation of the severe CD4+ T-cell loss caused by a pathogenic simian–human immunodeficiency virus by replacement of the subtype B vpu with the vpu from a subtype C HIV-1 clinical isolate

AbstractPreviously, we showed that the Vpu protein from subtype C human immunodeficiency virus type 1 (HIV-1) was efficiently targeted to the cell surface, suggesting that this protein has biological properties that differ from the well-studied subtype B Vpu protein. In this study, we have further analyzed the biological properties of the subtype C Vpu protein. Flow cytometric analysis revealed that the subtype B Vpu (strain HXB2) was more efficient at down-regulating CD4 surface expression than the Vpu proteins from four subtype C clinical isolates. We constructed a simian-human immunodeficiency virus virus, designated as SHIVSCVpu, in which the subtype B vpu gene from the pathogenic SHIVKU-1bMC33 was substituted with the vpu from a clinical isolate of subtype C HIV-1 (strain C.96.BW16B01). Cell culture studies revealed that SHIVSCVpu replicated with slightly reduced kinetics when compared with the parental SHIVKU-1bMC33 and that the viral Env and Gag precursor proteins were synthesized and processed similarly compared to the parental SHIVKU-1bMC33. To determine if substitution of the subtype C Vpu protein affected the pathogenesis of the virus, three pig-tailed macaques were inoculated with SHIVSCVpu and circulating CD4+ T-cell levels and viral loads were monitored for up to 44 weeks. Our results show that SHIVSCVpu caused a more gradual decline in the rate of CD4+ T cells in pig-tailed macaques compared to those inoculated with parental subtype B SHIVKU-1bMC33. These results show for the first time that different Vpu proteins of HIV-1 can influence the rate at which CD4+ T-cell loss occurs in the SHIV/pig-tailed macaque model

A Hitchhiker's guide through the bio-image analysis software universe

Modern research in the life sciences is unthinkable without computational methods for extracting, quantifying and visualising information derived from microscopy imaging data of biological samples. In the past decade, we observed a dramatic increase in available software packages for these purposes. As it is increasingly difficult to keep track of the number of available image analysis platforms, tool collections, components and emerging technologies, we provide a conservative overview of software that we use in daily routine and give insights into emerging new tools. We give guidance on which aspects to consider when choosing the platform that best suits the user's needs, including aspects such as image data type, skills of the team, infrastructure and community at the institute and availability of time and budget.Peer reviewe

Fix Your Membrane Receptor Imaging: Actin Cytoskeleton and CD4 Membrane Organization Disruption by Chemical Fixation

Single-molecule localization microscopy (SMLM) techniques allow near molecular scale resolution (~ 20 nm) as well as precise and robust analysis of protein organization at different scales. SMLM hardware, analytics and probes have been the focus of a variety of studies and are now commonly used in laboratories across the world. Protocol reliability and artifact identification are increasingly seen as important aspects of super-resolution microscopy. The reliability of these approaches thus requires in-depth evaluation so that biological findings are based on solid foundations. Here we explore how different fixation approaches that disrupt or preserve the actin cytoskeleton affect membrane protein organization. Using CD4 as a model, we show that fixation-mediated disruption of the actin cytoskeleton correlates with changes in CD4 membrane organization. We highlight how these artifacts are easy to overlook and how careful sample preparation is essential for extracting meaningful results from super-resolution microscopy

Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression

Chemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce histone hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition of HDACs plays any part in the normal physiological regulation of transcription. Using both in vitro and in vivo assays, we show that lactate, which accumulates when glycolysis exceeds the cell’s aerobic metabolic capacity, is an endogenous HDAC inhibitor, deregulating transcription in an HDAC-dependent manner. Lactate is a relatively weak inhibitor (IC(50) 40 mM) compared to the established inhibitors trichostatin A and butyrate, but the genes deregulated overlap significantly with those affected by low concentrations of the more potent inhibitors. HDAC inhibition causes significant up and downregulation of genes, but genes that are associated with HDAC proteins are more likely to be upregulated and less likely to be downregulated than would be expected. Our results suggest that the primary effect of HDAC inhibition by endogenous short-chain fatty acids like lactate is to promote gene expression at genes associated with HDAC proteins. Therefore, we propose that lactate may be an important transcriptional regulator, linking the metabolic state of the cell to gene transcription

Loss of Integrin-linked kinase sensitizes breast cancer to SRC inhibitors

SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, SRC tyrosine kinase inhibitors have so far failed to live up to their promise in clinical trials, with poor overall response rates. We aimed to identify possible synergistic gene–drug interactions to discover new rational combination therapies for SRC inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen in a model of triple-negative breast cancer revealed that loss of integrin-linked kinase (ILK) and its binding partners α-Parvin and PINCH-1 sensitizes cells to bosutinib, a clinically approved SRC/ABL kinase inhibitor. Sensitivity to bosutinib did not correlate with ABL dependency; instead, bosutinib likely induces these effects by acting as a SRC tyrosine kinase inhibitor. Furthermore, in vitro and in vivo models showed that loss of ILK enhanced sensitivity to eCF506, a novel and highly selective inhibitor of SRC with a unique mode of action. Whole-genome RNA sequencing following bosutinib treatment in ILK knockout cells identified broad changes in the expression of genes regulating cell adhesion and cell–extracellular matrix. Increased sensitivity to SRC inhibition in ILK knockout cells was associated with defective adhesion, resulting in reduced cell number as well as increased G(1) arrest and apoptosis. These findings support the potential of ILK loss as an exploitable therapeutic vulnerability in breast cancer, enhancing the effectiveness of clinical SRC inhibitors. SIGNIFICANCE: A CRISPR-Cas9 screen reveals that loss of integrin-linked kinase synergizes with SRC inhibition, providing a new opportunity for enhancing the clinical effectiveness of SRC inhibitors in breast cancer

Технология и техника сооружения разведочно-эксплуатационной скважины для водоснабжения школы села Некрасово (Томская область)

Объект исследования: артезианские скважины, необходимые для подведения водоснабжения школы села Некрасово (Томская область). Цель работы: разработка проекта на разведочно-эксплуатационное бурение артезианских скважин по данному объекту. Метод проведения работ: изучение, анализ, разработка.Object of the study: artesian wells needed to supply water to the school in the village of Nekrasovo (Tomsk region). Purpose of work: development of the project for exploration and production drilling of artesian wells for this facility. Method of work: study, analysis, development