An NADH-controlled gatekeeper of ATP synthase

Summary ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase. This interaction is NADH dependent and influenced by glycolysis, linking it to the cell’s metabolic state. Genetic interference with AIFM1/AK2 association impedes the ability of Caenorhabditis elegans animals to handle altered metabolic rates and nutrient availability. Together, the results imply AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis. This metabolic signal relay balances ATP synthase substrate supply against ATP conservation, enabling cells to adapt to fluctuating energy availability, with possible implications for AIFM1-related mitochondrial diseases

Validation of a performance-based driving assessment:Implications for licensing young drivers

Introduction: The on-road behind-the-wheel “practical” license test is the gate by which aspiring drivers must pass in order to drive independently in many jurisdictions. Evidence linking practical test performance and future driving outcomes is mixed. In the United States, license tests are characterized by high pass rates. A more rigorous test might dissuade applicants who are not ready from attempting the test, encourage better preparation, and also sensitize aspirational drivers to their areas of strengths and weaknesses; this is especially important for young, novice drivers. Methods: The purpose of this analysis was to detail the validation and implementation of the Drivingly On-Road Driver Assessment (DORA) to inform the debate on adopting a more challenging license test for young drivers and to describe the frequency of critical errors committed. Dyads randomized to the intervention arm of the Drivingly trial and who participated in the DORA were analyzed (n = 453 adolescents). The DORA was administered in live-traffic by a certified instructor at the end of the state learner’s permit holding period. Critical errors were assessed. Drivers self-reported practice hours and number of license test attempts following the DORA. Driver licenses were authenticated by the study team. Enrollment ran from 8/18/2021 to 12/15/2023. Results: Learner drivers passing the practical test the first-time had fewer critical errors on the DORA than those who took 3 + attempts or who delayed license-testing (p < 0.0001). Practice was inversely associated with errors (p < 0.001). Commission of critical errors was common, yet 317(70%) of learner drivers were licensed in one practical test attempt. Conclusions: The DORA validly assesses driving performance. Practical Implications: Changing state practical driver licensing examinations to be more comprehensive and rigorous could enhance traffic safety

Understanding Contact Angle Hysteresis: The Case of Slippery Micro-Patterned Biphilic Liquid-Like Surfaces

Shedding droplets and bubbles from surfaces is important in a wide range of practical situations, such as keeping windows dry, preventing icing, and heat transfer during nucleate boiling. A challenge for understanding these processes is the influence of pinning in hindering contact line motion. Here we report the pinning caused by square patterns of hydrophilic microscopic areas within a hydrophobic surface where both possess ultra-low contact angle hysteresis (ca. 3 degrees). The surfaces are created using a new lithographic method to pattern circular areas of a hydrophilic PEG-based slippery covalently-attached liquid surface (SCALS) within a hydrophobic PDMS-based SCALS background. We observe that at low (<35%) or high (>65%) Cassie surface area fractions for one component of the surface, the increase in droplet pinning in roll-off experiments can be described by a strong dilute defects model. In the intermediate range, droplets exhibit contact line faceting, with roll-off angles becoming more scattered. We find a single parameter a=0.54 +/- 0.04 can be used to fit our data for both cases of the hydrophilic areas regarded as defects within a hydrophobic background and the hydrophobic areas regarded as defects within a hydrophilic background. Finally, we propose an equation for the strength of pinning force per defect as a function of the two contact angles and a defect shape factor. These results are relevant for situations, such as self-cleaning and anti-icing, where pinning of droplets dominates the surface’s liquid-shedding properties, or in phase-change based heat transfer where the inverse problem is the shedding of bubbles

Live Demonstration: Hardware/Software Co-Design to Exploit RRAM Programmability for Emerging Edge Classification Using ArC TWO

In this demonstration, we present a hardware/software co-design methodology for Convolutional Neural Networks, where the classification section is managed through Resistive RAMs (RRAMs). To this aim, RRAM arrays are mounted onto the ArC TWO instrumentation board, which is interfaced to a laptop. A software Python front-end executes convolutional layers for feature extraction, generates stimuli for RRAMs, and controls the instrumentation board. As a proof of concept, handwritten digits classification is exhibited.</p

Quantifying the carbon footprint of canine breed-specific surgical care in a veterinary referral setting

Objective To develop and apply a calculator to quantify the carbon footprint of breed-specific surgical care in dogs, from hospital admission to discharge, in a veterinary referral setting. Materials and methods Breed-specific procedures were defined as surgeries performed uniquely or predominantly in particular breeds due to inherited or conformational pathology, as identified by the relevant clinical services. All dogs undergoing breed-specific procedures at a UK veterinary referral hospital over an eight-month period were prospectively studied. Data collected included procedure type, diagnostic imaging, anaesthesia, pharmaceuticals, surgical waste, travel distance, and personal protective equipment use. Published carbon conversion factors were applied to calculate the carbon footprint (kg CO₂e) for each component of care and the total per-patient emissions. Results Data were collected from 41 patients undergoing breed-specific surgeries. The mean carbon footprint per patient was calculated to be 103kg CO2e (standard deviation ± 47.5, range 33–220kg CO2e). Mean carbon footprint per patient for breed-specific procedures was; BOAS 100kg CO2e (standard deviation ± 36.4, range 49-174kg CO2e), medial canthoplasty 55kg CO2e (standard deviation ± 20.3, range 33-89kg CO2e), screw tail caudectomy 120kg CO2e (standard deviation ± 22.6, range 104-136kg CO2e), ‘Y’ fracture 159kg CO2e (standard deviation ± 48.2, range 103-211kg CO2e), ‘Y’ fracture and prophylactic humeral transcondylar screw 200kg CO2e (standard deviation ± 28.9, range 180-220kg CO2e) and prophylactic unilateral or bilateral humeral transcondylar screw 99kg CO2e (standard deviation ± 15.9, range 84-115kg CO2e) (Table 2). The largest contributors were pharmaceuticals excluding volatile agents (mean 55kg CO₂e, 40-67% of procedure-based emissions), owner travel (mean 19kg CO₂e, 9-28% of procedure-based emissions), and volatile agents (14kg CO₂e, 8-24% of procedure-based emissions). Diagnostic imaging accounted for 6kg CO₂e (0-8% of procedure-based emissions). Conclusions Breed-related procedures generate substantial carbon emissions, with pharmaceuticals and owner travel being major contributors. These findings provide a foundation for identifying environmentally impactful practices and support efforts to improve sustainability in referral veterinary care. This study also prompts broader ethical reflection on the environmental cost of inherited breed disorders, offering a new dimension to discussions on animal welfare, responsible breeding, and sustainability in companion animal medicine

The pandemic of poverty:Analysing the economic legacies of the pandemic

The COVID-19 pandemic brought unprecedented disruption to South African livelihoods. However, this disruption was unequally felt. During the height of the pandemic lockdown, most could not work, while many lost their employment. In a labour force that was already characterised by a myriad of poorly paid and precarious work, this disruption exacerbated poverty in the country. This study explores the economic impacts of the pandemic using quantitative data. It examines pandemic-related intertemporal relative deprivation (IRD); that is the feeling of deprivation that arises when individuals compare their current situation with their past circumstances. The study examines IRD during the heart of the pandemic (i.e., between early 2020 and late 2021). Data from the South African Social Attitudes Survey (N=2,996) was used for this study. Data analysis shows that levels of IRD are unevenly felt across South Africa. The analysis finds that IRD was negatively correlated with support for the political system in the country. Experiencing IRD bred distrust in the African National Congress, reduced satisfaction with political leaders, and increased democratic discontent. The article investigates the main drivers of pandemic-related IRD. Study analysis showed that IRD was associated with Coronavirus exposure as well as micro-level inequality

Variant Scoring Tools for Deep Mutational Scanning

Deep mutational scanning (DMS) can systematically assess the effects of thousands ofgenetic variants in a single assay, providing insights into protein function, evolution,host-pathogen interactions, and clinical impacts. Accurate scoring of variant effects iscrucial, yet the diversity of tools and experimental designs contributes considerableheterogeneity that complicates data analysis. Here, we review and compare 12computational tools for processing DMS sequencing data and scoring variant effects.We systematically outline each tool's statistical approaches, supported experimentaldesigns, input/output requirements, software implementation, visualisationcapabilities, and key assumptions. By highlighting the strengths and limitations of thesetools, we hope to guide researchers in selecting methods appropriate for their specificexperiments. Furthermore, we discuss current challenges, including the need forstandardised analysis protocols and sustainable software maintenance, as well asopportunities for future methods development. Ultimately, this review seeks toadvance the application and adoption of DMS, facilitating deeper biologicalunderstanding and improved clinical translation

Integrated investment, retrofit and abandonment planning of energy systems with short-term and long-term uncertainty using enhanced Benders decomposition

We propose the REORIENT (REnewable resOuRce Investment for the ENergy Transition) model for energy systems planning with the following novelties: (1) integrating capacity expansion, retrofit and abandonment planning, and (2) using multi-horizon stochastic mixed-integer linear programming with multi-timescale uncertainty. We apply the model to the European energy system considering: (a) investment in new hydrogen infrastructures, (b) capacity expansion of the European power system, (c) retrofitting oil and gas infrastructures in the North Sea region for hydrogen production and distribution, and abandoning existing infrastructures, and (d) long-term uncertainty in oil and gas prices and short-term uncertainty in time series parameters. We utilise the structure of multi-horizon stochastic programming and propose a stabilised adaptive Benders decomposition to solve the model efficiently. We first conduct a sensitivity analysis on retrofitting costs of oil and gas infrastructures. We then compare the REORIENT model with a conventional investment planning model regarding costs and investment decisions. Finally, the computational performance of the algorithm is presented. The results show that: (1) when the retrofitting cost is below 20% of the cost of building new ones, retrofitting is economical for most of the existing pipelines, (2) platform clusters keep producing oil due to the massive profit, and the clusters are abandoned in the last investment stage, (3) compared with a traditional investment planning model, the REORIENT model yields 24% lower investment cost in the North Sea region, and (4) the enhanced Benders algorithm is up to 6.8 times faster than the level method stabilised adaptive Benders.</p

Flow-Induced Vibration of an Underwater Lazy Wave Cable in Unidirectional Current

This paper describes measurements of the flow-induced vibration of an instrumented model cable in a lazy wave configuration immersed in unidirectional currents in the 2 m deep FloWave Facility at the University of Edinburgh. The cable model, designed to represent a dynamic power cable used in offshore renewable energy structures for electricity transmission, has an external diameter (D) of 31 mm and a mass ratio of 1.22. The current speed was varied from 0.1 to 0.9 m/s and its direction was set at 0, 90, and 180 degrees relative to the initial longitudinal axis of the cable. An underwater Qualisys motion capture system measured the in-line (IL) and cross-flow (CF) displacement components at 36 locations along the length of the submerged cable. Local displacements, response frequencies, and travelling wave modes are determined for reduced velocity Ur ϵ (5.29, 47.69), and Reynolds number Re ϵ (103, 104). It is found that the root mean square (RMS) values of the displacement components exhibited an increasing trend with reduced velocity reaching 0.40D in the in-line direction and 0.45D in the cross-flow direction. For reduced velocity in the range from 5.29 to 10.58, the cable exhibited single frequency vibrations. For Ur &gt; 10.58, the cable experienced broad-banded, multi-frequency responses. Along the cable, certain locations were found to execute distinct circular, elliptical, nearly linear, and figure-of- eight orbits at low Ur. A sudden phase shift was observed along the cable length, related to unsteady vortex-induced vibration (VIV), which effectively prevented lock-in occurring at high Ur

A multicenter, retrospective analysis of long-term survival in 255 dogs with pheochromocytoma treated with alpha-adrenoreceptor antagonists or surgery (2010 – 2021)

Background: The survival of dogs with pheochromocytoma (PCC) treated with adrenoreceptor antagonists has not been described or compared to surgically managed cases. Hypothesis/Objectives: The objective of this study is to evaluate the survival of medically and surgically managed dogs with PCC and investigate factors associated with survival. Animals: Two hundred fifty-five dogs with PCC, treated with alpha-adrenoreceptor antagonists (AA) without adrenalectomy (Group 1, n = 75), adrenalectomy +/– AA (Group 2, n = 128), or neither treatment (Group 3, n = 52). Methods: Retrospective, multicenter review of medical records. Median overall survival time (OST) for Groups 1 and 2 combined was calculated using Kaplan–Meier estimates, and then compared between Group 1 and Group 2 using Log-Rank testing. Cox proportional hazard analysis identified factors associated with survival in Groups 1 and 2 individually and combined. Results: Median OST for all cases was 854 (95% CI: 572–1136) days. Median OST was lower in Group 1 (247 days, 95% CI: 76–418 days) than in Group 2 (927 days, 95% CI: 587–1267 days; p &lt; 0.001). In Group 2, 88/92 dogs (97.8%) that received presurgical AA treatment survived to discharge compared to 23/27 (85.2%) that did not receive AA pretreatment (p = 0.03). Lack of clinical signs at presentation was associated with increased survival in both groups combined (HR 0.5; 95% CI 0.3–0.9; p = 0.02) and in Group 2 alone (HR 0.3; 95% CI 0.1–0.7; p = 0.01). Conclusions and Clinical Importance: Dogs with PCC treated with adrenalectomy have longer survival compared to those managed with AA without adrenalectomy.</p