803 research outputs found

    Delivery actuator for a transcervical sterilization device

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    The use of delivery systems in the human body for positioning and deploying implants, such as closure devices, dilation balloons, stents, coils and sterilization devices, are gaining more importance to preclude surgical incisions and general anesthesia. The majorities of the non-surgical medical devices are delivered in a low profile into human body form and subsequently require specialized operations for their deployment and release. An analogous procedure for permanent female sterilization is the transcervical approach that does not require either general anesthesia or surgical incision and uses a normal body passage. The objective of this paper is to detail the design, development and verification of an ergonomic actuator for a medical application. In particular, this actuator is designed for the deployment and release of an implant to achieve instant permanent female sterilization via the transcervical approach. This implant is deployed under hysteroscopic visualization and requires a sequence of rotary and linear operations for its deployment and release. More specifically, this manually operated actuator is a hand held device designed to transmit the required forces in a particular sequence to effect both implant deployment and release at a target location. In order to design the actuator and to investigate its mechanical behavior, a three-dimensional (3D) Computer Aided Design (CAD) model was developed and Finite Element Method (FEM) was used for simulations and optimization. Actuator validation was performed following a number of successful bench-top in-air deployments and in-vitro deployments in animal tissue and explanted human uteri. During these deployments it was observed that the actuator applied the required forces to the implant resulting in successful deployment. Initial results suggest that this actuator can be used single handedly during the deployment phase. The ongoing enhancement of this actuator is moving towards ā€œfirst-in- manā€ clinical trials

    On the Deployment of Cognitive Relay as Underlay Systems

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    The objective of this paper is to extend the idea of Cognitive Relay (CR). CR, as a secondary user, follows an underlay paradigm to endorse secondary usage of the spectrum to the indoor devices. To seek a spatial opportunity, i.e., deciding its transmission over the primary user channels, CR models its deployment scenario and the movements of the primary receivers and indoor devices. Modeling is beneficial for theoretical analysis, however it is also important to ensure the performance of CR in a real scenario. We consider briefly, the challenges involved while deploying a hardware prototype of such a system.Comment: 6 pages, 7 figures, 4 tables, accepted in Proceedings of CrownCom 2014, Oulu (Finland), June 2-4, 201

    Cellā€“cell signaling drives the evolution of complex traits: introductionā€”lung evo-devo

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    Physiology integrates biology with the environment through cellā€“cell interactions at multiple levels. The evolution of the respiratory system has been ā€œdeconvolutedā€ (Torday and Rehan in Am J Respir Cell Mol Biol 31:8ā€“12, 2004) through Gene Regulatory Networks (GRNs) applied to cellā€“cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, homeostasis, and regeneration based on evolutionary principles. This cellā€“cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar myocytes into alveolar adipocytes was critical for the evolution of the lung in land dwelling animals adapting to fluctuating Phanarezoic oxygen levels over the past 500 million years. Adipocytes prevent lung injury due to oxygen radicals and facilitate the rise of endothermy. In addition, they produce the class I cytokine leptin, which augments pulmonary surfactant activity and alveolar surface area, increasing selection pressure for both respiratory oxygenation and metabolic demand initially constrained by high-systemic vascular pressure, but subsequently compensated by the evolution of the adrenomedullary beta-adrenergic receptor mechanism. Conserted positive selection for the lung and adrenals created further selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Developmentally, increasing heart complexity and size impinges precociously on the gut mesoderm to induce the liver. That evolutionary-developmental interaction is significant because the liver provides regulated sources of glucose and glycogen to the evolving physiologic system, which is necessary for the evolution of the neocortex. Evolution of neocortical control furthers integration of physiologic systems. Such an evolutionary vertical integration of cell-to-tissue-to-organ-to-physiology of intrinsic cellā€“cell signaling and extrinsic factors is the reverse of the ā€œtop-downā€ conventional way in which physiologic systems are usually regarded. This novel mechanistic approach, incorporating a ā€œmiddle-outā€ cellā€“cell signaling component, will lead to a readily available algorithm for integrating genes and phenotypes. This symposium surveyed the phylogenetic origins of such vertically integrated mechanisms for the evolution of cellā€“cell communication as the basis for complex physiologic traits, from sponges to man

    Limitations of Protein Structure Prediction Algorithms in Therapeutic Protein Development

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    The three-dimensional protein structure is pivotal in comprehending biological phenomena. It directly governs protein function and hence aids in drug discovery. The development of protein prediction algorithms, such as AlphaFold2, ESMFold, and trRosetta, has given much hope in expediting protein-based therapeutic discovery. Though no study has reported a conclusive application of these algorithms, the efforts continue with much optimism. We intended to test the application of these algorithms in rank-ordering therapeutic proteins for their instability during the pre-translational modification stages, as may be predicted according to the confidence of the structure predicted by these algorithms. The selected molecules were based on a harmonized category of licensed therapeutic proteins; out of the 204 licensed products, 188 that were not conjugated were chosen for analysis, resulting in a lack of correlation between the confidence scores and structural or protein properties. It is crucial to note here that the predictive accuracy of these algorithms is contingent upon the presence of the known structure of the protein in the accessible database. Consequently, our conclusion emphasizes that these algorithms primarily replicate information derived from existing structures. While our findings caution against relying on these algorithms for drug discovery purposes, we acknowledge the need for a nuanced interpretation. Considering their limitations and recognizing that their utility may be constrained to scenarios where known structures are available is important. Hence, caution is advised when applying these algorithms to characterize various attributes of therapeutic proteins without the support of adequate structural information. It is worth noting that the two main algorithms, AlfphaFold2 and ESMFold, also showed a 72% correlation in their scores, pointing to similar limitations. While much progress has been made in computational sciences, the Levinthal paradox remains unsolved
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