The role of physics in multiomics and cancer evolution

Complex interactions between the physical environment and phenotype of a tumour, and genomics, transcriptomics, proteomics and epigenomics, are increasingly known to have a significant influence on cancer development, progression and evolution. For example, mechanical stress can alter both genome maintenance and histone modifications, which consequently affect transcription and the epigenome. Increased stiffness has been linked to genetic heterogeneity and is responsible for heterochromatin accumulations. Stiffness thereby leads to deregulation in gene expression, disrupts the proteome and can impact angiogenesis. Several studies have shown how the physics of cancer can influence diverse cancer hallmarks such as resistance to cell death, angiogenesis and evasion from immune destruction. In this review, we will explain the role that physics of cancer plays in cancer evolution and explore how multiomics are being used to elucidate the mechanisms underpinning them

Quantitative Image Processing for Three-Dimensional Episcopic Images of Biological Structures: Current State and Future Directions

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field

Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer

BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state

Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer

BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state

Im Geiste Jean Monnets: Rezension zu "The Economic Integration of Europe" von Richard Pomfret

Richard Pomfret: The Economic Integration of Europe. Cambridge, MA: Harvard University Press 2021. 978-0-674-24413-

Douleurs neuropathiques à l’officine : rôle du pharmacien dans leur prise en charge et dans la délivrance du Lyrica® (prégabaline)

Cette thèse s’intéresse à deux notions intriquées : le cas complexe des douleurs neuropathiques, ainsi que les problématiques gravitant autour d’un de ses principaux traitements, à savoir la prégabaline (Lyrica).Elle aborde de manière globale ce type de douleurs, en effectuant dans un premier temps des rappels de physiopathologie et en s’intéressant à leur diagnostic. Elle brosse ensuite l’ensemble des approches thérapeutiques disponibles, qu’elles soient médicamenteuses ou non, en s’appuyant entre autres sur les recommandations françaises établies en 2020 par des neurologues et médecins spécialisés dans la douleur, supervisées et validées par l’IASP (International Association for the Study of Pain).Elle enchaine sur la toxicomanie associée à la prégabaline, en se basant sur les rapports des observatoires européens, notamment au Royaume-Uni, en Finlande et en France, ce sujet nécessitant une vigilance particulière du pharmacien d’officine. Elle se termine enfin sur une étude de terrain menée sur les patients d’une pharmacie de quartier de Marseille concernant leur rapport vis-à-vis de leurs douleurs neuropathiques, ainsi que l’impact de leur traitement sur leur pathologie et sur leur qualité de vie. Les résultats sont tout aussi variés que le profil des patients et mériteraient de plus amples études

Real-time hand pose estimation on a smart-phone using Deep Learning

Hand pose estimation is a computer vision challenge that consists of detecting the coordinates of a hand’s key points in an image. This research investigates several deep learning-based solutions to determine whether or not it is possible to improve current state-of-the-art detectors for smartphone applications. Several models are tested and compared based on accuracy, processing speed and memory size. A final network is selected and detailed to compare it to the state-of-the-art. The proposed solution is obtained by combining the Differentiable Spatial to Numerical Transform layer to predict numerical coordinates together with the Fire module presented in the SqueezeNet architecture. This deep neural network contains around 1 million parameters and is able to outperform the current best documented model in all the metrics described above. A qualitative analysis is also performed to examine the predictions of the final solution on test images.Att bestämma en hands orientering är en utmaning inom bildanalys som består i att detektera koordinaterna för olika nyckelpunkter för handen i en bild. I denna studie undersöks ett antal metoder baserade på djupinlärning för att avgöra huruvida det är möjligt att förbättra existerande detektorer för tillämpningar på smartphones. Flera olika modeller testas och jämförs baserat på noggrannhet, beräkningshastighet och minneskrav. Ett slutligt nätverk väljs, analyseras och jämföras med nuvarande state-of-the-art teknik. Den lösning som föreslås erhålls genom att kombinera ett så kallat Differentiable Spatial to Numerical Transform-lager, för att förutsäga numeriska koordinater, tillsammans med en så kallad Fire-modul som tidigare presenteras som en del av arkitekturen SqueezeNet. Detta djupa neurala nätverk innehåller cirka en miljon parametrar och kan överträffa den nuvarande mest dokumenterade modellen i alla de avseenden som beskrivits ovan. En kvalitativ analys utförs också för att undersöka den slutliga lösningens uppskattningar på testbilder

Control of barley yellow dwarf virus (BYDV) in oat and wheat and identification of a RAPD marker associated with BYDV tolerance in oat

Populations of F\sb2 and F\sb3 plants from intraspecific spring oat (Avena sativa L.) crosses were grown in the greenhouse using a modified single-seed descent method with 100 plants per 15 cm pot. Subpopulations were inoculated with the BYDV-PAV-IL strain (1) in the F\sb2 generations only, and (2) in the F\sb2 and F\sb3 generations, using viruliferous aphids (Rhopalosiphum padi L.). These subpopulations were compared to uninoculated subpopulations. Inoculation did not increase the frequency of BYDV tolerant genotypes in the four crosses studied.The transmission characteristics of wingless (nymphs and apterous adults) viruliferous R. padi after access to oat treated with different rates of imidacloprid, a seed-treatment insecticide, were compared. After access to treated plants, aphid fecundity was reduced, aphids walked and fed atypically, and often abandoned the host plant. Aphids transmitted the virus to both treated and untreated plants, but the percentage of infected insecticide-treated seedlings was half that of untreated seedlings.The control of barley yellow dwarf using imidacloprid at three rates (0.6, 1.2 and 1.8 g a.i. Kg\sp{-1}) was studied in two oat and four soft red winter wheat cultivars in six-row plots. All insecticide treatments decreased the percentage of infected plants. Compared to untreated plots, yields were increased 112% and 35% in 1992 and 1993, respectively, in treated plots of a moderately susceptible oat cultivar inoculated with viruliferous aphids carrying BYDV-PAV-IL. In insecticide-treated plots of a tolerant oat cultivar, yields increased 23% and 21% in 1992 and 1993, respectively, compared to untreated plots. Yield increases of up to 21% were observed in treated plots of a susceptible wheat cultivar inoculated with viruliferous aphids carrying BYDV-PAV-IL. For all wheat cultivars, yield was negatively correlated with the percent disease incidence, and positively correlated with test weight and the calculated number of seeds tiller\sp{-1}. Test weight was negatively correlated with kernel weight.A RAPD marker associated with a gene for BYDV tolerance was identified in neat-isogenic lines (NILs) differing in BYDV tolerance. The NILs were derived by backcrossing with the sensitive cultivar Clintland 64 as recurrent parent to tolerant parents Ogle, IL 86-5698, IL 86-6404, and IL 86-1156 as donor parents. A polymorphic band is present in the donor parents and most BYDV tolerant NILs, but absent in the recurrent parent. The marker is associated with a gene for BYDV tolerance in NILs of IL 86-5698 x Clintland 64 and of IL 86-1156 x Clintland 64. The marker is not associated with BYDV tolerance in the two groups of NILs derived from backcross involving Ogle x Clintland 64 and IL 86-6404 x Clintland 64.U of I OnlyETDs are only available to UIUC Users without author permissio