Evaluation of process simulation for metal additive manufacturing, analyzation for oral maxillofacial surgery & depiction of fracture mechanics for human tibia

Evaluation of Process Simulation for Metal Additive Manufacturing, Analyzation for oral maxillofacial surgery & Depiction of fracture mechanics for human tibi

Using microbes to remove microplastics from wastewater and sewage sludge

Microplastics are a widespread form of plastic pollution. There is increasing evidence that they are a threat to human health and the environment. Microplastics in domestic and industrial wastewater become concentrated in sewage sludge during wastewater treatment processes. In 2020, water companies in England produced more than 800,000 tonnes of sewage sludge from urban wastewater. More than 90% of UK sewage sludge is spread on agricultural land as a fertilizer and soil conditioner. This provides a pathway for microplastics to enter the terrestrial environment. There is currently no UK legislation defining safe limits for microplastics in sludge and soils but future regulation is a possibility. There is currently no technology available to remove microplastics from wastewater treatment processes or the resulting sludge. Safe limits for microplastics in treated sewage sludge, soils and water bodies should be identified. This will require a survey of the extent of microplastic pollution throughout the UK, including concentration, identity and characteristics of microplastics in each environmental reservoir, and understanding how microplastics affect different living organisms. Microbes or fungi that break down plastic could be added to existing wastewater treatment process to remove microplastics and prevent their release into the environment. Alternatively, only the active enzymes (rather than the live microorganisms) could be added to the process. Currently, only polyester microplastics (11% of the total microplastic burden) could be treated in this way. Different microorganisms would have to be discovered or developed to tackle other common microplastic polymers such as polypropylene or polyethylene

Stress distribution throughout the craniofacial region following the maxillary expansion - a finite element analysis study

Stress Distribution Throughout the Craniofacial Region Following the Maxillary Expansion - A Finite Element Analysis Stud

Structure of the transmembrane protein 2 (TMEM2) ectodomain and its apparent lack of hyaluronidase activity

Background: Hyaluronic acid (HA) is a major polysaccharide component of the extracellular matrix. HA has essential functions in tissue architecture and the regulation of cell behaviour. HA turnover needs to be finely balanced. Increased HA degradation is associated with cancer, inflammation, and other pathological situations. Transmembrane protein 2 (TMEM2) is a cell surface protein that has been reported to degrade HA into ~5 kDa fragments and play an essential role in systemic HA turnover. Methods: We produced the soluble TMEM2 ectodomain (residues 106-1383; sTMEM2) in human embryonic kidney cells (HEK293) and determined its structure using X-ray crystallography. We tested sTMEM2 hyaluronidase activity using fluorescently labelled HA and size fractionation of reaction products. We tested HA binding in solution and using a glycan microarray. Results: Our crystal structure of sTMEM2 confirms a remarkably accurate prediction by AlphaFold. sTMEM2 contains a parallel β-helix typical of other polysaccharide-degrading enzymes, but an active site cannot be assigned with confidence. A lectin-like domain is inserted into the β-helix and predicted to be functional in carbohydrate binding. A second lectin-like domain at the C-terminus is unlikely to bind carbohydrates. We did not observe HA binding in two assay formats, suggesting a modest affinity at best. Unexpectedly, we were unable to observe any HA degradation by sTMEM2. Our negative results set an upper limit for k cat of approximately 10 -5 min -1. Conclusions: Although sTMEM2 contains domain types consistent with its suggested role in TMEM2 degradation, its hyaluronidase activity was undetectable. HA degradation by TMEM2 may require additional proteins and/or localisation at the cell surface

Eosinophils and tissue remodeling: relevance to airway disease

The ability of human tissue to reorganize and restore its existing structure underlies tissue homeostasis in the healthy airways, but in disease can persist without normal resolution, leading to an altered airway structure. Eosinophils play a cardinal role in airway remodeling both in health and disease, driving epithelial homeostasis and extracellular matrix turnover. Physiological consequences associated with eosinophil-driven remodeling include impaired lung function and reduced bronchodilator reversibility in asthma, and obstructed airflow in chronic rhinosinusitis with nasal polyps (CRSwNP). Given the contribution of airway remodeling to the development and persistence of symptoms in airways disease, targeting remodeling is an important therapeutic consideration. Indeed, there is early evidence that eosinophil attenuation may reduce remodeling and disease progression in asthma. This review provides an overview of tissue remodeling in both health and airway disease with a particular focus on eosinophilic asthma and CRSwNP, as well as the role of eosinophils in these processes and the implications for therapeutic interventions. Areas for future research are also noted, to help improve our understanding of the homeostatic and pathological roles of eosinophils in tissue remodeling, which should aid the development of targeted and effective treatments for eosinophilic diseases of the airways

Methods for embedding cell-free protein synthesis reactions in macro-scale hydrogels

Synthetic gene networks provide a platform for scientists and engineers to design and build novel systems with functionality encoded at a genetic level. While the dominant paradigm for the deployment of gene networks is within a cellular chassis, synthetic gene networks may also be deployed in cell-free environments. Promising applications of cell-free gene networks include biosensors, as these devices have been demonstrated against biotic (Ebola, Zika, and SARS-CoV-2 viruses) and abiotic (heavy metals, sulfides, pesticides, and other organic contaminants) targets. Cell-free systems are typically deployed in liquid form within a reaction vessel. Being able to embed such reactions in a physical matrix, however, may facilitate their broader application in a wider set of environments. To this end, methods for embedding cell-free protein synthesis (CFPS) reactions in a variety of hydrogel matrices have been developed. One of the key properties of hydrogels conducive to this work is the high-water reconstitution capacity of hydrogel materials. Additionally, hydrogels possess physical and chemical characteristics that are functionally beneficial. Hydrogels can be freeze-dried for storage and rehydrated for use later. Two step-by-step protocols for the inclusion and assay of CFPS reactions in hydrogels are presented. First, a CFPS system can be incorporated into a hydrogel via rehydration with a cell lysate. The system within the hydrogel can then be induced or expressed constitutively for complete protein expression through the hydrogel. Second, cell lysate can be introduced to a hydrogel at the point of polymerization, and the entire system can be freeze-dried and rehydrated at a later point with an aqueous solution containing the inducer for the expression system encoded within the hydrogel. These methods have the potential to allow for cell-free gene networks that confer sensory capabilities to hydrogel materials, with the potential for deployment beyond the laboratory

Protein structure-based evaluation of missense variants: Resources, challenges and future directions.

We provide an overview of the methods that can be used for protein structure-based evaluation of missense variants. The algorithms can be broadly divided into those that calculate the difference in free energy (ΔΔG) between the wild type and variant structures and those that use structural features to predict the damaging effect of a variant without providing a ΔΔG. A wide range of machine learning approaches have been employed to develop those algorithms. We also discuss challenges and opportunities for variant interpretation in view of the recent breakthrough in three-dimensional structural modelling using deep learning

Novel approaches to study the design principles of turing patterns

A fundamental concern in biology is the origins of, and the mechanisms responsible for the structures and patterns observed within, organisms [1]. Turing patterns and the Turing mechanism may explain the processes behind biological pattern formation. Theoretical studies of the Turing mechanism show that it is highly sensitive to fluctuations and variations in kinetic parameters. Various experiments have shown that biochemical processes in living cells are inherently noisy systems, they are subjected to a diverse range of fluctuations. This ‘robustness problem’ raises the question of how such a seemingly sensitive mechanism could produce robust patterns amidst noise [2]. Recent computational advances allow for large-scale explorations of the design space of regulatory networks underpinning pattern production. Such explorations generate insights into the Turing mechanism’s robustness and sensitivity. Part 1 of the thesis performs a large-scale exploration within a discrete modelling framework, identifying the same pattern producing network types identified within previous studies. The equivalence we find across modelling frameworks suggests that a deeper underlying principle of these Turing mechanisms exist. In contrast to the continuous case , networks appear to be more robust in the discrete framework we explore here, suggesting that these networks might be more robust than previously thought. Part 2 of the thesis focuses on Turing patterns as a inverse problem: is it possible to infer the parameters that most likely produced a given pattern? Here, we distill the information of a pattern into a one-dimensional representation based on resistance distances, a concept from electrical networks [3]. We shown this representation to be robust against fluctuations in the pattern stemming from random initial conditions, or stochasticity of the model, and therefore permits the application of machine learning methods such as neural networks and support vector regression for parameter inference. We apply this method to infer one and three parameters for both deterministic and stochastic models of the Gierer-Meinhardt system. We show that the ’resistance distance histogram’ method is more robust to noise, and performs better for limited number of data samples than a vanilla convolutional neural network approach. Robustness of parameter inference with respect to noise and limited data samples is of particular importance when considering real experimental data. Overall, this thesis advances our understanding on the design principles of pattern formation, and provides insight into possible methods for inferring details of regulatory networks behind experimental evidence of Turing patterns.Open Acces

Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: the ASCOT study

BACKGROUND/AIMS: To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). METHODS: A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. RESULTS: 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. CONCLUSION: The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. TRIAL REGISTRATION NUMBER: NCT02873026

'Condoms are hard to get by': access to HIV prevention methods during lockdown of the COVID-19 epidemic in eastern Zimbabwe

BACKGROUND: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, health services were disrupted worldwide, including HIV prevention services. While some studies have begun to document the effects of COVID-19 on HIV prevention, little has been done to qualitatively examine how lockdown measures were experienced and perceived to affect access to HIV prevention methods in sub-Saharan Africa. OBJECTIVES: To explore how the COVID-19 pandemic was perceived to affect access to HIV prevention methods in eastern Zimbabwe. METHOD: This article draws on qualitative data from the first three data collection points (involving telephone interviews, group discussions, and photography) of a telephone and WhatsApp-enabled digital ethnography. Data were collected from 11 adolescent girls and young women and five men over a 5-month period (March-July 2021). The data were analysed thematically. RESULTS: Participants reported widespread interruption to their condom supply when beerhalls were shut down as part of a nationwide lockdown. Restrictions in movement meant that participants who could afford to buy condoms from larger supermarkets or pharmacies were unable to. Additionally, the police reportedly refused to issue letters granting permission to travel for the purpose of accessing HIV prevention services. The COVID-19 pandemic was also described to obstruct the demand (fear of COVID-19, movement restrictions) and supply (de-prioritised, stock-outs) for HIV prevention services. Nonetheless, under certain formal and informal circumstances, such as accessing other and more prioritised health services, or 'knowing the right people', some participants were able to access HIV prevention methods. CONCLUSION: People at risk of HIV experienced the COVID-19 epidemic in Zimbabwe as disruptive to access to HIV prevention methods. While the disruptions were temporary, they were long enough to catalyse local responses, and to highlight the need for future pandemic response capacities to circumvent a reversal of hard-won gains in HIV prevention