Seepage forces, important factors in the formation of horizontal hydraulic fractures and bedding-parallel fibrous veins ('beef' and 'cone-in-cone')

International audienceBedding-parallel fibrous veins ('beef' and 'cone-in-cone') are common to a number of sedimentary basins, especially those containing black shale. The type locality is SW England. The commonest mineral in the fibres is calcite. The fibres indicate vertical opening, against the force of gravity. In the past, this has been attributed to fluid overpressure. However, a simple analysis, based on Von Terzaghi's concepts, leads to the conclusion that, for the fractures to be horizontal, either the rock must be anisotropic, or it must be subject to horizontal compression. By means of a more complete analysis, supported by physical models, we show that horizontal fractures are to be expected, even if the rock is isotropic and there are no tectonic stresses. Upward fluid flow, in response to an overpressure gradient, imparts seepage forces to all elements of the solid framework. The seepage forces counteract the weight of the rock, and even surpass it, generating a tensile effective stress. The process may lead, either to tensile hydraulic fracturing, or to dilatant shear failure. We suggest that these two failure modes, and the availability of suitable solutes, explain the frequent occurrence of 'beef' and 'cone-in-cone' respectively

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Insights in the exhumation history of the NWZagros frombedrock and detrital apatite fission-track analysis: evidence for a long-lived orogeny

We present the ¢rst ¢ssion-track (FT) thermochronology results for theNWZagrosBelt (SWIran) in order to identify denudation episodes that occurred during the protracted Zagros orogeny. Samples were collected from the two main detrital successions of the NWZagros foreland basin: the Palaeocene^early Eocene Amiran^Kashkan succession and theMiocene Agha Jari and Bakhtyari Formations. In situ bedrock samples were furthermore collected in the Sanandaj-Sirjan Zone. Only apatite ¢ssion-track (AFT) data have been successfully obtained, including 26 ages and11track-length distributions. Five families of AFTages have been documented from analyses of in situ bedrock and detrital samples: pre-middle Jurassic at 171 and 225Ma, early^late Cretaceous at 91Ma, Maastrichtian at 66Ma,middle^late Eocene at 38Ma and Oligocene^early Miocene at 22Ma.The most widespread middle^late Eocene cooling phase, around 38Ma, is documented by a predominant grain-age population in Agha Jari sediments and by cooling ages of a granitic boulder sample. AFTages document at least three cooling/denudation periods linked to major geodynamic events related to the Zagros orogeny, during the lateCretaceous oceanic obduction event, during the middle and late Eocene and during the earlyMiocene. Both late Cretaceous and early Miocene orogenic processes produced bending of the Arabian plate and concomitant foreland deposition. Between the two major £exural foreland episodes, the middle^late Eocene phase mostly produced a long-lasting slow- or nondepositional episode in the inner part of the foreland basin, whereas deposition and tectonics migrated to theNE along the Sanandaj-Sirjan domain and its Gaveh Rud fore-arc basin. As evidenced in this study, the Zagros orogeny was long-lived and multiepisodic, implying that the timing of accretion of the di¡erent tectonic domains that form the Zagros Mountains requires cautious interpretation

An internal ribosome entry site in the 5′ untranslated region of epidermal growth factor receptor allows hypoxic expression

The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5′ untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5′ UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates

Logistical Barriers in Accessing Emergency Healthcare for Rural Asthmatics: A Patient’s Perspective

Australia has a high prevalence of asthma amongst its population. Literature shows rural asthma patients have a higher need to access emergency healthcare due to asthma-related emergencies than those living in metropolitan areas, and that underutilisation of ambulance resources is evident in rural areas. This study aims to explore the barriers preventing patients from accessing emergency healthcare resources during an asthma-related emergency in rural New South Wales (NSW). A qualitative interpretative design comprising 12 semi-structured interviews was conducted between May and July 2021. Participants had accessed emergency healthcare in rural NSW during a moderate to severe asthma exacerbation in NSW within the last five years. Interviews were recorded and transcribed verbatim to allow thematic analysis, which produced four overarching themes. This paper explores two of those themes due to the depth and range of the data. The impact of healthcare logistics, including access and availability of emergency healthcare resources, response times, environmental concerns, and issues with transport home from the hospital, were identified as barriers. Additionally, financial cost, the presumed cost to healthcare workers and societal cost were also found to influence participants’ decisions to access emergency healthcare. Overall, multiple factors were identified as potential barriers to asthma patients in rural NSW accessing emergency healthcare. Introducing improved mapping systems and mobile/radio reception, in addition to better staff resourcing in rural locations may help reduce the reluctance of asthma patients to access healthcare due to logistical concerns and fear of being a burden on the emergency healthcare system. Keywords: asthma, emergency healthcare, health literacy, rural, self-management ____________________________________  Obstacles logistiques à l’accès aux soins de santé d’urgence pour les patients asthmatiques ruraux :Le point de vue d’un patient RésuméL'Australie a une prévalence élevée d'asthme parmi sa population. La littérature montre que les patients asthmatiques ruraux ont plus besoin d’accéder à des soins de santé d’urgence en raison d’urgences liées à l’asthme que ceux vivant dans les zones métropolitaines, et que la sous-utilisation des ressources ambulancières est évidente dans les zones rurales. Cette étude vise à explorer les obstacles empêchant les patients d'accéder aux ressources de soins de santé d'urgence lors d'une urgence liée à l'asthme dans les zones rurales de la Nouvelle-Galles du Sud (NGS). Une conception interprétative qualitative comprenant 12 entretiens semi-structurés a été menée entre mai et juillet 2021. Les participants avaient eu accès à des soins de santé d'urgence dans les zones rurales de la NGS lors d'une exacerbation de l'asthme modérée à sévère en NGS au cours des cinq dernières années. Les entretiens ont été enregistrés et transcrits textuellement pour permettre une analyse thématique, qui a produit quatre thèmes généraux. Cet article explore deux de ces thèmes en raison de la profondeur et de la portée des données. L’impact de la logistique des soins de santé, notamment l’accès et la disponibilité des ressources de soins de santé d’urgence, les délais de réponse, les préoccupations environnementales et les problèmes de transport depuis l’hôpital vers le domicile, ont été identifiés comme des obstacles. De plus, il a été constaté que le coût financier, le coût présumé pour les travailleurs de la santé et le coût sociétal influencent également les décisions des participants d’accéder aux soins de santé d’urgence. Dans l’ensemble, plusieurs facteurs ont été identifiés comme obstacles potentiels à l’accès des patients asthmatiques des zones rurales de la NGS aux soins de santé d’urgence. L'introduction de systèmes de cartographie améliorés et d'une réception mobile/radio, ainsi qu'une meilleure dotation en personnel dans les zones rurales, pourraient contribuer à réduire la réticence des patients asthmatiques à accéder aux soins de santé en raison de problèmes logistiques et de la peur de constituer un fardeau pour le système de soins de santé d'urgence. Mots clés : Asthme, soins de santé d’urgence, littératie en santé, milieu rural, autogestio

Learn!Bio—A time-limited cross-sectional study on biosciences students’ pathway to resilience during and post the Covid-19 pandemic at a UK university from 2020–2023 and insights into future teaching approaches

Higher education in biosciences is substantiallyinformed by hands-on field trips and practical laboratory skills-training. With the first Covid-19 national lock-down in England in March 2020, on-campus education at higher education institutions was swiftly moved to alternative provisions, including online only options, a mix of synchronous or asynchronous blended, or hybrid adaptions. Students enrolled on an undergraduate bioscience programme have been faced with unprecedented changes and interruptions to their education. This study aimed to evaluate bioscience students’ ability to adjust to a fast-evolving learning environment and to capture students’ journey building up resilience and graduate attributes. A total of 317 Bioscience undergraduate students in years 1–3 at the biology department at a northwest English university participated in this anonymous, cross-sectional, mixed-method study with open and closed questions evaluating their perception and feedback to remote and blended learning provisions during the Covid-19 pandemic and post pandemic learning capturing academic years 2019/20–2022/23. The Covid-19 pandemic and the consequent restriction of personal social interaction resulted in an significant decrease in the mental wellbeing of undergraduate bioscience students in this study, cumulating in poor or very poor self-rating of wellbeing in spring 2021; while at the same time students showed evidence of advanced adaption to the new learning and social environment by acquisition of additional technical, social and professional graduate-level skills. Post pandemic, bioscience students worry about the increased living costs and are strongly in favour of a mixture of face-to-face and blended learning approaches. Our results show that bioscience students can self-report poor mental health while developing resilience, indicating tailored support can aid in developing students’ resilience. Students have adjusted with ease to digital teaching provisions and now expect higher education institutions continue to offer both, face-to-face, and blended teaching, reducing the burden on students’ notably risen living costs

Identification of supershear transition mechanisms due to material contrast at bimaterial faults

Numerical modelling of dynamic rupture is conducted along faults separating similar and dissimilar materials. Supershear transition is enhanced in the direction of slip of the stiffer material (the negative direction) due to the bimaterial effect whereby a decrease in normal stress in front of the crack tip supports yielding ahead of the rupture. In the direction of slip of the more compliant material (the positive direction), an increase in normal stress ahead of the rupture tip delays or prevents the supershear transition, whereas the impact of the bimaterial effect on subshear ruptures is to promote rupture in the positive direction due to the tensile stress perturbation behind the rupture tip in this direction. We demonstrate that the material contrast and the parameter S control whether the transition from sub- to supershear velocity (supershear transition) is smooth or follows the Burridge–Andrews mechanism. Supershear transition along interfaces separating dissimilar materials is possible for higher values of the parameter S than supershear transition along material interfaces separating similar materials. The difference between pulse-like and crack-like rupture is small with regard to the supershear transition type

Fitness for purpose in vocational higher education : relationship between entry requirements and student attainment in occupational therapy degree programmes.

This thesis explores the relationship between the level of entry requirements and subsequent student attainment on Occupational Therapy degree programmes. It questions the justification for the continued rise in the level of entry qualifications since the early 1990s. It also considers whether students' personal qualities should be seen as equally important when considering entry to a vocational programme. The thesis begins With a review of the evoiution of Occupational Therapy as a profession and considers the development of training courses from diploma through to degree validation. A range of literature is discussed in relation to the role of qualifications in education and training including degrees in the training of professionals and issues of professional competence. An empirical investigation, using quantitative and qualitative methods was conducted of the relationship between entry requirements and student attainment at an English university where an Occupational Therapy degree programme has been placed since 1991. A questionnaire survey provided details of the students' entry qualifications which were then considered alongside evidence of students' progress and attainment during the programme and their final degree classification. Interviews were conducted with lecturers at the university and employers of the new graduates. The findings of this thesis did not find any academic rationale to support the rise in entry qualifications. Rather, the results indicate that had the entry standards been strictly adhered to, a high percentage of students would not have been eligible to train. Furthermore, the thesis establishes that more importance should be given to the role of interviewing prospective students

Asymptotic Theory for Rayleigh and Rayleigh-Type Waves

Explicit asymptotic formulations are derived for Rayleigh and Rayleigh-type interfacial and edge waves. The hyperbolic–elliptic duality of surface and interfacial waves is established, along with the parabolic–elliptic duality of the dispersive edge wave on a Kirchhoff plate. The effects of anisotropy, piezoelectricity, thin elastic coatings, and mixed boundary conditions are taken into consideration. The advantages of the developed approach are illustrated by steady-state and transient problems for a moving load on an elastic half-space

Signaling from mTOR to eIF2α mediates cell migration in response to the chemotherapeutic doxorubicin.

After exposure to cytotoxic chemotherapeutics, tumor cells alter their translatome to promote cell survival programs through the regulation of eukaryotic initiation factor 4F (eIF4F) and ternary complex. Compounds that block mTOR signaling and eIF4F complex formation, such as rapamycin and its analogs, have been used in combination therapies to enhance cell killing, although their success has been limited. This is likely because the cross-talk between signaling pathways that coordinate eIF4F regulation with ternary complex formation after treatment with genotoxic therapeutics has not been fully explored. Here, we described a regulatory pathway downstream of p53 in which inhibition of mTOR after DNA damage promoted cross-talk signaling and led to eIF2α phosphorylation. We showed that eIF2α phosphorylation did not inhibit protein synthesis but was instead required for cell migration and that pharmacologically blocking this pathway with either ISRIB or trazodone limited cell migration. These results support the notion that therapeutic targeting of eIF2α signaling could restrict tumor cell metastasis and invasion and could be beneficial to subsets of patients with cancer.R.F.H. was supported by MRC studentship and Wellcome Trust (grant number 110071/Z/15/Z). A.E.W., T.A.A.P., and M.S. were supported by MRC Programme funding (MC_UP_A600_1023