Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in .

Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation.

Model-based design of a pneumatic actuator for a dynamically reconfigurable socket for transtibial amputees.

In this work, a cost-effective, scalable pneumatic silicone actuator array is introduced, designed to dynamically conform to the user's skin and thereby alleviate localised pressure within a prosthetic socket. The appropriate constitutive models for developing a finite element representation of these actuators are systematically identified, parametrised, and validated. Employing this computational framework, the surface deformation fields induced by 270 variations in soft actuator array design parameters under realistic load conditions are examined, achieving predictive accuracies within 70 µm.

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug).

Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses.

Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion.

Characterizing the Effect of Repetitive Head Impact Exposure and mTBI on Adolescent Collision Sports Players' Brain with Diffusion Magnetic Resonance Imaging.

Athletes in collision sports frequently sustain repetitive head impacts (RHI), which, while not individually severe enough for a clinical mild traumatic brain injury (mTBI) diagnosis, can compromise neuronal organization by transferring mechanical energy to the brain. Although numerous studies target athletes with mTBI, there is a lack of longitudinal research on young collision sport participants, highlighting an unaddressed concern regarding cumulative RHI effects on brain microstructures. Therefore, this study aimed to investigate the microstructural changes in the brains' of high school rugby players due to repeated head impacts and to establish a correlation between clinical symptoms, cumulative effects of RHI exposure, and changes in the brain's microstructure.