University of Portsmouth

• We designed a multi-epitope-based vaccine candidate against Mycobacterium tuberculosis (MTB) through an in-silico approach . • Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. • Simulations predicted elevated levels of CD4 and CD8, T- lymphocytes, B- lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. • While the construct showed high antigenicity and lacked allergenic or toxic properties, this study demonstrated the potentials of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. Mycobacterium tuberculosis (MTB) remains a global health challenge, necessitating innovative strategies to enhance control and prevention. The emergence of drug-resistant MTB strains underscores the need for advanced tuberculosis (TB) vaccines beyond the Bacillus Calmette-Guérin (BCG). This study used computational approaches to design a multi-epitope MTB vaccine. Conserved antigenic proteins (PE_PGRS, ESAT-6, and CFP-10) were identified via MTB genome analyses from the NCBI database. Cytotoxic T cell (CTL), helper T cell (HTL), and B cell epitopes were predicted using the Immune Epitope Database (IEDB) and assembled with adjuvants and linkers to optimize stability and immunogenicity. The vaccine construct underwent rigorous assessments of epitope mapping, allergenicity, antigenicity, and tertiary structural modeling. Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. The final construct, consisting of 512 amino acids and a molecular weight of 48,937.61 Da, demonstrated favorable structural and immunological attributes, including 91% of residues in acceptable regions (Ramachandran analysis). Simulations predicted elevated levels of CD4 and CD8 T lymphocytes, B lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. Additionally, the vaccine was successfully cloned into an Escherichia coli (strain K12) pET-28a (+) plasmid for expression analysis. This study highlights the promise of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. While the construct showed high antigenicity and lacked allergenic or toxic properties, further in vivo evaluations are crucial for confirming human efficacy.

Alcohol use is driven not only by environmental cues but also by individual differences in motivational style. Recent work has demonstrated how memory cues can reduce subsequent desire for alcohol, yet it remains unclear how personality traits shape this effect. To address this, we recruited male and female participants ( N = 169) who completed the behavioural inhibition/approach system (BIS/BAS) scales and were then cued to recall either a previous alcohol drinking episode and estimate the number of alcohol calories consumed (Alcohol Cue, AC) or a control (Neutral Cue, NC). They then rated their desire for alcohol (DAQ). Findings revealed lower desire for those in the AC compared to NC group and separately, a positive association between alcohol desire and BAS and particularly BAS-Drive. We further found that a measure of residual BAS (BAS less BIS) was positively related to desire but did not moderate the effect of memory cue. These findings suggest that being reminded of a previous drinking episode can exert a modest but consistent influence on alcohol desire. • Memory of a recent drinking episode reduced alcohol desire in males and females. • Increases in Behavioural Approach System (BAS) increased alcohol desire. • BAS did not moderate the effect of the alcohol memory cue. • Memory cues could offer a simple method of reducing alcohol desire.

Professional standards are used to inform and measure educational programs and individual credentialling of many professions, including those in allied health. The objective of this project was to develop consensus on international professional standards for clinical exercise physiologists. The project employed an e-Delphi approach to build a consensus, being guided by a steering committee and an expert working group. The expert working group reviewed the elements and the steering committee overviewed the results of each round. The expert working group were invited to consider whether elements should be included or excluded and, if to be included, whether these should be core or non-core. The wording of the elements was also checked for accuracy. To be included in the end professional standards and as core, each element required 80% consensus from the expert working group. The e-Delphi process found consensus on four overarching professional standard domains for clinical exercise physiology: professional practice; foundational knowledge; assessment and client management; and case formulation anddesign and delivery of evidence-based interventions. Consensus was also achieved on individual elements. All bar two of the elements were accepted as core, with these two both being included in the professional standards since they were close to meeting the 80% consensus threshold and because they are reflected in the clinical exercise physiology professional standards where this profession is established. The international professional standards consensus has been achieved with the aim of supporting the development of a standardised approach to international education and practice in clinical exercise physiology.

Synthesizer is a fast, flexible, modular, and extensible Python package that empowers astronomers to turn theoretical galaxy models into realistic synthetic observations-including spectra, photometry, images, and spectral cubes-with a focus on interchangeable modelling assumptions.By offloading computationally intensive tasks to threaded C++ extensions, Synthesizer delivers both simplicity and speed, enabling rapid forward-modelling workflows without requiring users to manage low-level data processing and computational details.

Survival rates for metastatic Ewing sarcoma (EwS) have remained persistently low over recent decades, highlighting the need for more effective chemotherapeutic options. Potential targets may be found within the Neuropeptide Y (NPY) signalling pathway that has been implicated in EwS cell survival. However, confounding factors include hypoxia that modulates NPY signalling, dipeptidyl peptidase-4 (DPP4/CD26) that cleaves NPY and interactions via NPY signalling from infiltrating immune cells. We investigated these interactions in A673 and SK-ES-1 EwS cell lines and THP-1 monocytes to identify therapeutic targets suitable for drug repurposing. Both EwS cell lines secreted NPY into conditioned media and extracellular vesicles. Recombinant NPY enhanced viability of both A673 and SK-ES-1 cells; however, the NPY1R antagonist BMS-193885 reduced viability in A673 cells only. Recombinant DPP4 widely promoted EwS viability and, under hypoxic conditions, it increased cell metabolism. The DPP4 inhibitor linagliptin, which is used clinically, consistently suppressed EwS viability with elevated sensitivity under hypoxia, where there was increased cell death of SK-ES-1 cells. Conversely, in THP-1 monocytes, NPY suppressed metabolism, BMS-193885 increased live-cell staining and DPP4 induced cell death. These findings suggest that NPY and DPP4 enhance EwS survival through autocrine/paracrine signalling while reducing monocyte viability. Thus, targeting the NPY/DPP4 signalling axis may provide therapeutic benefit by directly suppressing EwS growth and enhancing efficacy of immunotherapy.

The dislodgement and transportation of boulders on rocky coasts by storm waves has been the subject of an increasing number of studies in the last decade. Research has been approached from different perspectives, such as numerical models that hindcast wave heights that produce movement, structural control on boulder production, and innovative monitoring and change detection techniques. However, the complex dynamics between boulders and wave forces that determine boulder mobility remain insufficiently understood.This ongoing study aims to document instances of boulder displacement and quantify their frequency over a two-year observation period. Monitoring is being conducted at three coastal sites across the Maltese Islands (Central Mediterranean): one in Qawra (northern coast) and two in Marsascala (southern coast). Data acquisition is conducted periodically using unmanned aerial vehicles (UAVs), with subsequent 3D model reconstruction performed using Agisoft Metashape. Each newly generated model is compared to its predecessor to detect changes in boulder positions.Observed boulder movement is evaluated based on key parameters including size, morphology, initial location, displacement distance, and direction of transport. These transport events are then correlated with wave conditions recorded during the interval between successive UAV surveys.Preliminary findings from the first six-month monitoring phase at Qawra are being presented here. These results suggest that boulder mobility is influenced by a combination of factors, including boulder morphometry and location, coastal topography, wave energy, and wave direction relative to shoreline orientation.

Modern day crustal evolution is controlled by plate tectonics. I-type magmatism dominates Phanerozoic crustal growth and has been extensively used to study modern subduction systems and slab-mantle interactions. In contrast, Archean geodynamics remain poorly constrained, with no consensus on the existence of a primitive form of plate tectonics or subduction. This uncertainty largely results from a preservation bias: most Archean crust has been destroyed, and the surviving rock record shows an overprint of billions of years of overlapping, non-mutually exclusive processes such as metamorphism or hydrothermal alteration. As a result, identifying primary geochemical signatures indicative of specific Archean geodynamic mechanisms is not straightforward. In this work, we present a viable Phanerozoic proxy to Archean geodynamics using a global assessment of geochemical and experimental data. A comparison between Phanerozoic post-collisional magmatism and the Archean sanukitoid suite reveals a conspicuous geochemical resemblance based on major and trace element criteria. This common signature is coherent with derivation from a metasomatized-mantle source. The requirement for mantle metasomatism by felsic, upper-crustal material implies a mechanism capable of juxtaposing upper crust with the lithospheric mantle, potentially through continental subduction. Although this geochemical parallel does not necessarily imply a tectonic analogy, it demands active geodynamics during the Archean capable of generating hybrid lithospheric sources. Together, these observations support the use of Phanerozoic magmatic analogues as a framework for investigating Archean geodynamic processes.

The aim of this study was to assess the effect of printing orientation and water ageing on the flexural strength and flexural modulus of 3D printed resins for occlusal splints. Bar-shaped specimens were designed with dimensions of 64 × 10 × 3.3 mm according to ISO 20795-2:2013. Specimens were 3D printed with the Form 3B printer (Formlabs), using Dental LT Clear Resin (CL) or Comfort Resin (CO) (Formlabs), and 3 different printing orientations: as per manufacturer's recommendation (40° N = 20), parallel (0° N = 20), or perpendicular to the build platform (90° N = 20). To simulate intraoral ageing, half of the specimens per material and printing orientation (N = 10) were stored in distilled water at 37 °C for 30 days prior to testing. Specimens were tested in a three-point bending apparatus using a universal testing machine equipped with a 50 N load cell moving at a crosshead speed of 5 mm/min. Flexural strength (MPa) and flexural modulus (GPa) data were collected and statistically processed with separate analyses for unaged and aged specimens (Two-Way or One-Way ANOVA; Tukey test; p < 0.05). As for unaged specimens, both resin materials exhibited the highest flexural strength and modulus in the 90° orientation and the lowest values in the 40° orientation group. After water aging, all groups showed reduced flexural strength and modulus, with CO displaying up to 52% loss in flexural strength and values falling below ISO thresholds. CO consistently exhibited significantly lower flexural strength and modulus than CL, irrespective of aging.