3D-Printed Hollow Microneedle-Lateral Flow Devices for Rapid Blood-Free Detection of C-Reactive Protein and Procalcitonin

\ua9 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.Hollow microneedle devices as a technology for interstitial fluid extraction show promise for the minimally invasive point-of-care detection of analytes. Despite increasing efforts toward on-patch diagnostics, the use of hollow microneedles has been limited due to the complexity caused by integrating hollow microneedles with established point-of-care diagnostic techniques. Herein, a 3D printing method is utilized, to provide low-cost manufacturing of custom-designed hollow microneedle devices, allowing for easy integration with lateral flow assays for rapid and blood-free diagnostics. Microneedle surface modification through PEGylation results in prolonged and enhanced hydrophilicity, enabling passive uptake of small volume samples (≈22.5 \ub5L) and an enhanced shelf life. The hollow microneedle devices are deemed non-cytotoxic to cell types found within the skin following short-term and prolonged exposure in accordance with ISO10993. Furthermore, the devices demonstrate high mechanical strength and successfully penetrate porcine skin grafts without damaging the surrounding skin morphology. This work also demonstrates for the first time the use of hollow microneedles for the simultaneous detection, at clinically relevant concentrations, of C-reactive protein (LoD = 10 \ub5g mL−1) and procalcitonin (LoD = 1 ng mL−1), through porcine skin, ultimately demonstrating the beneficial use of manufactured 3D-printed hollow microneedles towards low-cost blood-free diagnostics of inflammation markers

Cervical spine injuries: A whole-body musculoskeletal model for the analysis of spinal loading

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Cervical spine trauma from sport or traffic collisions can have devastating consequences for individuals and a high societal cost. The precise mechanisms of such injuries are still unknown as investigation is hampered by the difficulty in experimentally replicating the conditions under which these injuries occur. We harness the benefits of computer simulation to report on the creation and validation of i) a generic musculoskeletal model (MASI) for the analyses of cervical spine loading in healthy subjects, and ii) a population-specific version of the model (Rugby Model), for investigating cervical spine injury mechanisms during rugby activities. The musculoskeletal models were created in OpenSim, and validated against in vivo data of a healthy subject and a rugby player performing neck and upper limb movements. The novel aspects of the Rugby Model comprise i) population-specific inertial properties and muscle parameters representing rugby forward players, and ii) a custom scapula-clavicular joint that allows the application of multiple external loads. We confirm the utility of the developed generic and population-specific models via verification steps and validation of kinematics, joint moments and neuromuscular activations during rugby scrummaging and neck functional movements, which achieve results comparable with in vivoand in vitrodata. The Rugby Model was validated and used for the first time to provide insight into anatomical loading and cervical spine injury mechanisms related to rugby, whilst the MASI introduces a new computational tool to allow investigation of spinal injuries arising from other sporting activities, transport, and ergonomic applications. The models used in this study are freely available at simtk.org and allow to integrate in silico analyses with experimental approaches in injury prevention.Funding: This project is funded by the Rugby Football Union (RFU) Injured Players Foundation. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Musculoskeletal modelling of the human cervical spine for the investigation of injury mechanisms during axial impacts

This is the final version. Available from Public Library of Science via the DOI in this record.All relevant data are available at Figshare [https://figshare.com/projects/SILVESTROS_PLOS_ONE_SUPPORTING_DOCUMENTS/58280] and musculoskeletal models and relevant project information is available on the OpenSim SimTK repository [https://simtk.org/projects/csibath].Head collisions in sport can result in catastrophic injuries to the cervical spine. Musculoskeletal modelling can help analyse the relationship between motion, external forces and internal loads that lead to injury. However, impact specific musculoskeletal models are lacking as current viscoelastic values used to describe cervical spine joint dynamics have been obtained from unrepresentative quasi-static or static experiments. The aim of this study was to develop and validate a cervical spine musculoskeletal model for use in axial impacts. Cervical spine specimens (C2-C6) were tested under measured sub-catastrophic loads and the resulting 3D motion of the vertebrae was measured. Specimen specific musculoskeletal models were then created and used to estimate the axial and shear viscoelastic (stiffness and damping) properties of the joints through an optimisation algorithm that minimised tracking errors between measured and simulated kinematics. A five-fold cross validation and a Monte Carlo sensitivity analysis were conducted to assess the performance of the newly estimated parameters. The impact-specific parameters were integrated in a population specific musculoskeletal model and used to assess cervical spine loads measured from Rugby union impacts compared to available models. Results of the optimisation showed a larger increase of axial joint stiffness compared to axial damping and shear viscoelastic parameters for all models. The sensitivity analysis revealed that lower values of axial stiffness and shear damping reduced the models performance considerably compared to other degrees of freedom. The impact-specific parameters integrated in the population specific model estimated more appropriate joint displacements for axial head impacts compared to available models and are therefore more suited for injury mechanism analysis.Rugby Football Union (RFU) Injured Players Foundatio

Molecular Characterization of Two Monoclonal Antibodies against the Same Epitope on B-Cell Receptor Associated Protein 31

published_or_final_versio

Machinability investigations of Inconel-800 super alloy under sustainable cooling conditions

With regard to the manufacturing of innovative hard-machining super alloys (i.e., Inconel-800), a potential alternative for improving the process is using a novel cutting fluid approach. Generally, the cutting fluids allow the maintenance of a better tool topography that can generate a superior surface quality of machined material. However, the chemical components of fluids involved in that process may produce harmful effects on human health and can trigger environmental concerns. By decreasing the cutting fluids amount while using sustainable methods (i.e., dry), Near Dry Machining (NDM) will be possible in order to resolve these problems. This paper discusses the features of two innovative techniques for machining an Inconel-800 superalloy by plain turning while considering some critical parameters such as the cutting force, surface characteristics (Ra), the tool wear rate, and chip morphology. The research findings highlight the near-dry machining process robustness over the dry machining routine while its great potential to resolve the heat transfer concerns in this manufacturing method was demonstrated. The results confirm other benefits of these methods (i.e., NDM) linked to the sustainability aspects in terms of the clean process, friendly environment, and permits as well as in terms of improving the manufacturing characteristics

A pyramid MOT with integrated optical cavities as a cold atom platform for an optical lattice clock

We realize a two-stage, hexagonal pyramid magneto-optical trap (MOT) with strontium, and demonstrate loading of cold atoms into cavity-enhanced 1D and 2D optical lattice traps, all within a single compact assembly of in-vacuum optics. We show that the device is suitable for high-performance quantum technologies, focusing especially on its intended application as a strontium optical lattice clock. We prepare 2 × 104 spin-polarized atoms of 87Sr in the optical lattice within 500 ms; we observe a vacuum-limited lifetime of atoms in the lattice of 27 s; and we measure a background DC electric field of 12 V m−1 from stray charges, corresponding to a fractional frequency shift of (−1.2 ± 0.8) × 10−18 to the strontium clock transition. When used in combination with careful management of the blackbody radiation environment, the device shows potential as a platform for realizing a compact, robust, transportable optical lattice clock with systematic uncertainty at the 10−18 level

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/μl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Beyond the Insider—Outsider Perspective: The Study of Religion as a Study of Discourse Construction

This essay reflects on contemporary theorizing of religion which embodies an explicit critique of the imperial project, seeing that by most common consent the scholarly disciplinary field of religious studies (history of religion, phenomenology of religion, Religionswissenschaft) is a late nineteenth century invention that coincides with the emergence of anthropology and ethnography as epiphenomena of the colonial project (whether as Orientalism or as exoticism the Other is rendered manageable subjects). The scholarly study of religion is, therefore, simultaneously a study of the history of theory and concept formation, and the social, cultural, and political work performed by such study and theorizing. The metatheory of the study of religion is a main focus of the essay. Alongside that, the essay focuses more pointedly on the concept of discourse, and considers the extraordinary situation where the same methodological vocabulary that functions in religious studies also functions in critical theological studies, which relativizes the division of ‘insider’ and ‘outsider’ perspectives. Yet both are conventionally practised either in isolation from each other as distinct theoretical and disciplinary bounded/defined study fields, or—the other and almost direct opposite—religious studies being performed in the context of theological study, situated in and offered by theological faculties. An overview of recent debates in the field of religious studies serves to highlight the continued struggle to demarcate the boundaries between the study of religion and the study of theology—in some of the recent, very strident debates mainstream religious studies is labelled as nothing more than theology. This contribution, then, aims at a kind of metatheoretical reflection on the study of religion and theology both as discourses that serve mythmaking, identity formation, culturally strategic purposes. That is, from the discourse perspective that is proposed here, it is possible to move beyond the definitional divide between religious studies and theology—even beyond ‘religion’ itself—to focus on the mundanely material practices that constitute that which is called religion. In the way in which the terms are used it is clear that the terminologies themselves bear the imprint of historical social discourses that occasioned the rise of their use. This essay, then, is something of a metacritique of the language of the study of religion—beyond religion, and beyond the study of religion and theology