The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation

Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction

Blade loss transient dynamics analysis, volume 1. Task 1: Survey and perspective

An analytical technique was developed to predict the behavior of a rotor system subjected to sudden unbalance. The technique is implemented in the Turbine Engine Transient Rotor Analysis (TETRA) computer program using the component element method. The analysis was particularly aimed toward blade-loss phenomena in gas turbine engines. A dual-rotor, casing, and pylon structure can be modeled by the computer program. Blade tip rubs, Coriolis forces, and mechanical clearances are included. The analytical system was verified by modeling and simulating actual test conditions for a rig test as well as a full-engine, blade-release demonstration

Blade loss transient dynamics analysis, volume 2. Task 2: Theoretical and analytical development. Task 3: Experimental verification

The component element method was used to develop a transient dynamic analysis computer program which is essentially based on modal synthesis combined with a central, finite difference, numerical integration scheme. The methodology leads to a modular or building-block technique that is amenable to computer programming. To verify the analytical method, turbine engine transient response analysis (TETRA), was applied to two blade-out test vehicles that had been previously instrumented and tested. Comparison of the time dependent test data with those predicted by TETRA led to recommendations for refinement or extension of the analytical method to improve its accuracy and overcome its shortcomings. The development of working equations, their discretization, numerical solution scheme, the modular concept of engine modelling, the program logical structure and some illustrated results are discussed. The blade-loss test vehicles (rig full engine), the type of measured data, and the engine structural model are described

Sustaining Educational Reforms in Introductory Physics

While it is well known which curricular practices can improve student performance on measures of conceptual understanding, the sustaining of these practices and the role of faculty members in implementing these practices are less well understood. We present a study of the hand-off of Tutorials in Introductory Physics from initial adopters to other instructors at the University of Colorado, including traditional faculty not involved in physics education research. The study examines the impact of implementation of Tutorials on student conceptual learning across eight first-semester, and seven second-semester courses, for fifteen faculty over twelve semesters, and includes roughly 4000 students. It is possible to demonstrate consistently high, and statistically indistinguishable, student learning gains for different faculty members; however, such results are not the norm, and appear to rely on a variety of factors. Student performance varies by faculty background - faculty involved in, or informed by physics education research, consistently post higher student learning gains than less-informed faculty. Student performance in these courses also varies by curricula used - all semesters in which the research-based Tutorials and Learning Assistants are used have higher student learning gains than those semesters that rely on non-research based materials and do not employ Learning Assistants.Comment: 21 pages, 4 figures, and other essential inf

Glucose-lactate metabolic cooperation in cancer: insights from a spatial mathematical model and implications for targeted therapy

A recent study has hypothesised a glucose–lactate metabolic symbiosis between adjacent hypoxic and oxygenated regions of a developing tumour, and proposed a treatment strategy to target this symbiosis. However, in vivo experimental support remains inconclusive. Here we develop a minimal spatial mathematical model of glucose–lactate metabolism to examine, in principle, whether metabolic symbiosis is plausible in human tumours, and to assess the potential impact of inhibiting it. We find that symbiosis is a robust feature of our model system—although on the length scale at which oxygen supply is diffusion-limited, its occurrence requires very high cellular metabolic activity—and that necrosis in the tumour core is reduced in the presence of symbiosis. Upon simulating therapeutic inhibition of lactate uptake, we predict that targeted treatment increases the extent of tissue oxygenation without increasing core necrosis. The oxygenation effect is correlated strongly with the extent of wild-type hypoxia and only weakly with wild-type symbiotic behaviour, and therefore may be promising for radiosensitisation of hypoxic, lactate-consuming tumours even if they do not exhibit a spatially well-defined symbiosis. Finally, we conduct in vitro experiments on the U87 glioblastoma cell line to facilitate preliminary speculation as to where highly malignant tumours might fall in our parameter space, and find that these experiments suggest a weakly symbiotic regime for U87 cells, thus raising the new question of what relationship might exist between symbiosis and tumour malignancy

Gender differences in experiences and expectations of haemodialysis in a frail and seriously unwell patient population

Introduction Surprisingly few studies have explored the experiences of seriously unwell people with kidney disease on haemodialysis therapy: we conducted a mixed-methods study to investigate gender differences in illness experience, symptom burden, treatment considerations or expectations in this cohort. Methods Seriously unwell people on haemodialysis (1-year mortality risk of >20%) at three hospital-based units were invited to take part in a structured interview or to complete the same questions independently via a questionnaire. 54 people took part (36 males, 18 females); data analysis was undertaken using a thematic approach. Results ‘Desire to keep living’ is the most important and basic thought process when starting dialysis. Fear also predominates influencing risk assessment and decision-making. Once fear is managed, there are physical, social, practical and emotional issues to rationalise, but choice only seems possible if shared decision-making is part of the consultation. Gender differences were seen in perceived hopes and expectations of treatment. Males were more likely to prioritise achievement of physical goals, with females prioritising a wish to feel well. Both genders reported significantly higher symptom scores than their healthcare provider perceived, however this difference was more marked in females. Dialysis regret existed in >50% of participants and 6/54 (11%) stated that they would have chosen no dialysis at all. Females were more likely to report feeling depressed (P=0.001). Conclusion Different genders approach treatment decisions and prioritise treatment expectations differently. Recognising this will allow personalised care plans to be developed and improve the experiences of seriously unwell people with kidney disease

Gender Differences in Experiences and Expectations of Hemodialysis in a Frail and Seriously Unwell Patient Population.

Surprisingly few studies have explored the experiences of seriously unwell people with kidney disease on hemodialysis therapy: we conducted a mixed-methods study to investigate gender differences in illness experience, symptom burden, treatment considerations or expectations in this cohort. Seriously unwell people on hemodialysis (1-year mortality risk of >20%) at 3 hospital-based units were invited to take part in a structured interview or to complete the same questions independently via a questionnaire. A total of 54 people took part (36 males, 18 females); data analysis was undertaken using a thematic approach. "Desire to keep living" is the most important and basic thought process when starting dialysis. Fear also predominates influencing risk assessment and decision-making. Once fear is managed, there are physical, social, practical and emotional issues to rationalize, but choice only seems possible if shared decision-making is part of the consultation.Gender differences were seen in perceived hopes and expectations of treatment. Males were more likely to prioritize achievement of physical goals, with females prioritizing a wish to feel well. Both genders reported significantly higher symptom scores than their health care provider perceived, however this difference was more marked in females. Dialysis regret existed in >50% of participants and 6 out of 54 (11%) stated that they would have chosen no dialysis at all. Females were more likely to report feeling depressed (  = 0.001). Different genders approach treatment decisions and prioritize treatment expectations differently. Recognizing this will allow personalized care plans to be developed and improve the experiences of seriously unwell people with kidney disease. [Abstract copyright: © 2022 International Society of Nephrology. Published by Elsevier Inc.

Modelling corneal epithelial wound closure in the presence of physiological electric fields via a moving boundary formalism

A new framework for the modelling of corneal epithelial wound healing is presented, which can include the presence of a physiological electric field. The difficulty inherent in the inclusion of this biological phenomenon motivates our use of a moving boundary formalism. A key conclusion is that the model predicts a linear relation between the wound healing speed and the physiological electric field strengths over a physiologically large range of electric field strength. Another key point is that this linear relationship between electric field strength and wound healing speed is robust to variations in critical parameters that are difficult to estimate. The linearity is also robust to different realizations of the modelling framework presented

Shell evolution of stable N = 50-56 Zr and Mo nuclei with respect to low-lying octupole excitations

For the N = 50-56 zirconium (Z = 40) and molybdenum (Z = 42) isotopes, the evolution of subshells is evaluated by extracting the effective single-particle energies from available particle-transfer data. The extracted systematic evolution of neutron subshells and the systematics of the excitation energy of the octupole phonons provide evidence for type-II shape coexistence in the Zr isotopes. Employing a simplistic approach, the relative effective single-particle energies are used to estimate whether the formation of low-lying octupole-isovector excitations is possible at the proposed energies. The results raise doubts about this assignment

Locus-specific expression of transposable elements in single cells with CELLO-seq

Transposable elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next-generation, single-cell sequencing technologies because their highly repetitive nature means that short complementary DNA reads cannot be unambiguously mapped to a specific locus. Single CELl LOng-read RNA-sequencing (CELLO-seq) combines long-read single cell RNA-sequencing with computational analyses to measure TE expression at unique loci. We used CELLO-seq to assess the widespread expression of TEs in two-cell mouse blastomeres as well as in human induced pluripotent stem cells. Across both species, old and young TEs showed evidence of locus-specific expression with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to the reference with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed large heterogeneity, with TEs within a class showing different patterns of correlation and suggesting distinct regulatory mechanisms