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The role of electric vehicle-to-X in net zero energy systems:A comprehensive review
No full textVehicle-to-X (V2X) incorporates the ability to transfer energy from electric vehicles (EVs), to appliances, homes, businesses, communities and electricity distribution networks. The role of EVs and V2X is developing rapidly and could yield substantial benefits in the transition to a net zero energy system. To understand recent developments in the field we conduct a review of 75 peer-reviewed articles published between 2018 and 2023. Recognising that distribution network operators and local governments are likely to play a significant role in grid integration and charging infrastructure the review focusses on the role of decentralised actors. There has been rapid technical innovation over this period, vehicle manufacturers are moving to include bi-directional charging within vehicle specifications, and we find a strong case for policy interventions that expedite the development of V2X. Realizing the full benefits of V2X will require collaboration within and between local and national government, and with distribution grids. From a local perspective, deployment of V2X could help to realise the full potential of local renewable energy generation, progress emission reductions, and reduce the investment needed in distribution network infrastructure. With appropriate interventions and targeting it could help to reduce energy and transport inequalities but the converse is also likely to apply. We identify barriers to the development of local and national policies on V2G, provide recommendations for policy-makers, and propose issues that would benefit from further research
Semantic and morphophonological productivity in the Kîîtharaka gender system:A quantitative study
No full textNominal classification systems are characterized by diverse and sometimes complex gender assignment rules that interact in dynamic ways. The specifics of how gender assignment works can vary widely from language to language. Nominal classification systems of Bantu languages in particular have been the subject of long-standing debate. Traditional accounts of gender assignment are based principally on abstract semantic features which have been found to be unreliable in at least some present-day Bantu languages. Such analyses, in addition to relying on arbitrary sets of semantic features, are problematic, since they provide no clear definition of what it means for a particular feature to be productive. Here we follow a more recent approach, using corpus data to evaluate productivity. We compiled a corpus of 2,327 Kîîtharaka nouns, each coded for a set of semantic and morphophonological features. We then used the Tolerance Principle (Yang, 2016) to measure the predicted productivity of each feature. Our results indicate that morphophonological features are highly productive in Kîîtharaka. However, of the tested semantic features, relatively few were predicted to be productive, including Human, and some evaluative features (Augmentative, Pejorative, Diminutive). The feature Human is in fact only productive for a specific subset of nouns, indicating a possible interaction between features. We discuss why this might be, and highlight the implications of this approach for Kîîtharaka, and for the study of gender assignment in Bantu more broadly
Association of Plasma Biomarkers With Longitudinal Atrophy and Microvascular Burden on MRI Across Neurodegenerative and Cerebrovascular Diseases
No full textDYF-5 regulates intraflagellar transport by affecting train turnaround
No full textIntraflagellar transport (IFT) coordinates the transport of cargo in cilia and is essential for ciliary function. CILK1 has been identified as a key regulator of IFT. The mechanism by which it acts has, however, remained unclear. In this study, we use fluorescence imaging and single-molecule tracking in the phasmid cilia of live Caenorhabditis elegans to study the effect of the CILK1 homologue DYF-5 on the dynamics of the IFT. We show that in the absence of DYF-5, IFT components accumulate at the ciliary tip. Kinesin-II is no longer restricted to the proximal segment of the cilium but is present throughout the cilium, while its velocity is different from that of OSM-3. The frequency of IFT trains is reduced and in particular retrograde trains were rarely observed. In the absence of DYF-5, retrograde transport is vastly reduced, resulting in the accumulation of IFT components at the tip and depletion at the base. The latter results in impeded anterograde train assembly, resulting in fewer trains with irregular composition. Our results show that DYF-5 plays a key role in regulating the turnarounds of IFT trains at the ciliary tip.</p
Diagnostic performance of the Enferplex Bovine TB antibody test using bulk tank milk samples from dairy cattle
No full textBovine tuberculosis, caused mainly by Mycobacterium bovis, is a major disease of cattle worldwide associated with significant economic losses and is usually diagnosed using periodic tuberculin skin tests, IFNγ release assay, or at postmortem. Recently, we developed a multiplex test for detecting antibodies to Mycobacterium bovis in cattle that has high sensitivity and specificity using serum or individual milk samples. Here, we assessed the performance of the test using bulk tank milk samples from skin test-positive and bovine tuberculosis-free cattle herds. In nonanamnestic bulk tank milk samples, the sensitivity relative to the comparative cervical skin test was 77.2% and the specificity was 99.8% using the high sensitivity setting of the antibody test. A kappa value of 0.85 was found, indicating almost perfect agreement between the test results and comparative cervical skin test status of the herds. Likelihood ratio analysis gave a positive likelihood ratio of 53.1 and a negative likelihood ratio of 0.030, indicating that the test provides good diagnostic evidence of the infection being either present or absent, respectively. Bulk tank milk samples from herds with inconclusive reactors to the comparative cervical skin test but had no reactors gave a test positivity of 73.7%, indicating that antibody-positive animals were present in the herd after removal of the reactors. Variances in herd prevalence did not result in statistically significant differences in test positivity, and the test was able to detect a herd prevalence of 0.1% of comparative cervical skin test reactors in 80% of low prevalence herds. The test showed good repeatability and reproducibility, giving complete concordance in results from 3 independent laboratories. The results show that the bulk milk antibody test could be used as a nonanamnestic surveillance tool for detecting and monitoring bovine tuberculosis in dairy cattle herds.</p
Perivascular space and white matter hyperintensities in Alzheimer's disease:associations with disease progression and cognitive function
No full textBACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD. This study aimed to investigate alterations in the function of the glymphatic system in individuals with AD versus healthy controls (HC), and to explore its association with Aβ, cerebrovascular disease (CVD), white matter hyperintensities (WMH), and cognitive function.METHODS: DTI MRI data from three independent study cohorts (ActiGliA: AD n = 16, Controls n = 18; DELCODE: AD n = 54, Controls n = 67; ADNI: AD n = 43, Controls n = 49) were used to evaluate the perivascular space (PVS) integrity; a potential biomarker for glymphatic activity. The DTI-Along the Perivascular Space technique was used to measure water diffusion along PVS providing an index to assess the efficiency of the glymphatic system's waste clearance function. WMH load was quantified in FLAIR MRI using the lesion segmentation tool. We quantified WMHs volume within our defined region of interest (ROI) and excluded participants with any WMHs to avoid confounding the ALPS-Index. Associations with cerebrospinal fluid (CSF) AD hallmark biomarkers, cognitive performance (MMSE) and clinical severity (CDR) were assessed.RESULTS: AD patients had a significantly lower ALPS-Index vs. healthy controls (ActiGliA: AD: mean = 1.22, SD = 0.12; Controls: mean = 1.36, SD = 0.14, p = 0.004; DELCODE: AD: mean = 1.26, SD = 0.18; Controls: mean = 1.34, SD = 0.2, p = 0.035; ADNI: AD: mean = 1.08, SD = 0.24; Controls: mean = 1.19, SD = 0.13, p = 0.008). The ALPS-Index was associated with CSF Aβ concentration, WMH number and MMSE and CDR. WMH, found in the ROIs correlated negatively with the ALPS-Index.CONCLUSIONS: This study highlights the potential of the DTI-ALPS-Index as a biomarker for glymphatic dysfunction in AD. It underscores the importance of considering vascular factors and the glymphatic system in the pathogenesis and diagnosis of AD as WMHs in the ROI could cause disturbances and inaccurate indices.</p
Computer-directed rational engineering of dioxygenase TcsAB for triclosan biodegradation under cold conditions
Get PDFThe dioxygenase TcsAB is a specific dioxygenase involved in the initial biodegradation of the broad-spectrum antibacterial agent triclosan (TCS). However, it exhibits significantly reduced activity under cold conditions. In this study, a computer-directed approach combining loop engineering and N-terminal truncation was utilized to decrease the thermostability of TcsAB, thereby enhancing its catalytic activity in cold environments. The iterative mutant TcsAB (TcsAY277P/F279P/S311W/A313WTcsBN-terminal truncation) exhibited a 2.54-fold greater catalytic efficiency than the wild type at 15°C. Molecular dynamics simulations showed that the mutations introduced in the substrate-binding pocket increased its flexibility, leading to enhanced catalytic activity through binding in a more advantageous conformation. This modified dioxygenase was employed as a biological component, and Pseudomonas knackmussii B13 was used as a chassis cell to construct an engineered strain for the efficient degradation of TCS at low temperatures. The objective was to enhance the capacity of TCS bioremediation in natural environments. Insights gained from this study may inform the rational redesign of enzymes related to the robustness of biodegradation of emerging contaminants
Proton Exchange Membrane Electrolysis Revisited: Advancements, Challenges, and Two-Phase Transport Insights in Materials and Modelling
Get PDFThe transition to clean energy has accelerated the pursuit of hydrogen as a sustainable fuel. Among various production methods, proton exchange membrane electrolysis cells (PEMECs) stand out due to their ability to generate ultra-pure hydrogen with efficiencies exceeding 80% and current densities reaching 2 A/cm2. Their compact design and rapid response to dynamic energy inputs make them ideal for integration with renewable energy sources. This review provides a comprehensive assessment of PEMEC technology, covering key internal components, system configurations, and efficiency improvements. The role of catalyst optimization, membrane advancements, and electrode architectures in enhancing performance is critically analyzed. Additionally, we examine state-of-the-art numerical modelling, comparing zero-dimensional to three-dimensional simulations and single-phase to two-phase flow dynamics. The impact of oxygen evolution and bubble dynamics on mass transport and performance is highlighted. Recent studies indicate that optimized electrode architectures can enhance mass transport efficiency by up to 20%, significantly improving PEMEC operation. Advancements in two-phase flow simulations are crucial for capturing multiphase transport effects, such as phase separation, electrolyte transport, and membrane hydration. However, challenges persist, including high catalyst costs, durability concerns, and scalable system designs. To address these, this review explores non-precious metal catalysts, nanostructured membranes, and machine-learning-assisted simulations, which have demonstrated cost reductions of up to 50% while maintaining electrochemical performance. Future research should integrate experimental validation with computational modelling to improve predictive accuracy and real-world performance. Addressing system control strategies for stable PEMEC operation under variable renewable energy conditions is essential for large-scale deployment. This review serves as a roadmap for future research, guiding the development of more efficient, durable, and economically viable PEM electrolyzers for green hydrogen production
Convergent depression of activity-dependent bulk endocytosis in rodent models of autism spectrum disorder
Get PDFBackgroundThe key pathological mechanisms underlying autism spectrum disorder (ASD) remain relatively undetermined, potentially due to the heterogenous nature of the condition. Targeted studies of a series of monogenic ASDs have revealed postsynaptic dysfunction as a central conserved mechanism. Presynaptic dysfunction is emerging as an additional disease locus in neurodevelopmental disorders; however, it is unclear whether this dysfunction drives ASD or is an adaptation to the altered brain microenvironment.MethodsTo differentiate between these two competing scenarios, we performed a high content analysis of key stages of the synaptic vesicle lifecycle in primary neuronal cultures derived from a series of preclinical rat models of monogenic ASD. These five independent models (Nrxn1+/−, Nlgn3−/y, Syngap+/−, Syngap+/Δ−GAP, Pten+/−) were specifically selected to have perturbations in a diverse palette of genes that were expressed either at the pre- or post-synapse. Synaptic vesicle exocytosis and cargo trafficking were triggered via two discrete trains of activity and monitored using the genetically-encoded reporter synaptophysin-pHluorin. Activity-dependent bulk endocytosis was assessed during intense neuronal activity using the fluid phase marker tetramethylrhodamine-dextran.ResultsBoth synaptic vesicle fusion events and cargo trafficking were unaffected in all models investigated under all stimulation protocols. However, a key convergent phenotype across neurons derived from all five models was revealed, a depression in activity-dependent bulk endocytosis.LimitationsThe study is exclusively conducted in primary cultures of hippocampal neurons; therefore, the impact on neurons from other brain regions or altered brain microcircuitry was not assessed. No molecular mechanism has been identified for this depression.ConclusionThis suggests that depression of activity-dependent bulk endocytosis is a presynaptic homeostatic mechanism to correct for intrinsic dysfunction in ASD neurons
Unequal access to diagnosis of myalgic encephalomyelitis in England
Get PDFBackgroundPeople with Myalgic Encephalomyelitis (ME/CFS; sometimes referred to as chronic fatigue syndrome) experience poor health-related quality of life and only rarely recover. ME/CFS has no curative treatment, and no single diagnostic test. Public health and policy decisions relevant to ME/CFS require knowledge of its prevalence and barriers to diagnosis. However, people with ME/CFS report lengthy diagnostic delays and prevalence estimates vary greatly due to uneven diagnosis and misdiagnosis. Factors that influence diagnosis could be revealed by stratifying a single population by gender, age and ethnicity.MethodsHospital Episode Statistics data, routinely collected by the NHS in England, was downloaded from the Feasibility Self-Service of NHS DigiTrials. This was used to stratify individuals with the ICD-10 code that best reflects ME/CFS symptoms (G93.3) according to age, self-reported gender and ethnicity, General Practice and NHS England Integrated Care Board (ICB).ResultsIn all, 100,055 people in England had been diagnosed with ME/CFS (ICD-10:G93.3) between April 1 1989 and October 7 2023, 0.16% of all registered patients. Of these, 79,445 were females and 20,590 males, a female-to-male ratio of 3.88:1. Female relative to male prevalence peaked at about 6-to-1 in individuals’ fourth and fifth decades of life. Prevalence varied widely across the 42 ICBs: 0.086%-0.82% for females and 0.024%-0.21% for males. White individuals were approximately 5-fold more likely to be diagnosed with ME/CFS than others; Black, Asian or Chinese ethnicities are associated with particularly low rates of ME/CFS diagnoses. This ethnicity bias is stronger than for other common diseases. Among active English GP practices, 176 (3%) had no registered ME/CFS patients. Eight ICBs (19%) each contained fewer than 8 other-than-white individuals with a G93.3 code despite their registers containing a total of 293,770 other-than-white patients.ConclusionOther-than-white ethnic groups, older females (>60y), older males (>80y), and people living in areas of multiple deprivation are disproportionately undiagnosed with ME/CFS. Lifetime prevalence of ME/CFS for English females and males may be as high as 0.92% and 0.25%, respectively, or approximately 404,000 UK individuals overall (0.6%). This improved estimate of ME/CFS prevalence allows more accurate assessment of the socioeconomic and disease burden imposed by ME/CFS.<br/
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