Antifreeze proteins (AFPs) are a class of ice-binding proteins that promote survival of a variety of cold-adapted organisms by decreasing the freezing temperature of bodily fluids. A growing number of biomedical, agricultural, and commercial products, such as organs, foods, and industrial fluids, have benefited from the ability of AFPs to control ice crystal growth and prevent ice recrystallization at subzero temperatures. One limitation of AFP use in these latter contexts is their tendency to denature and irreversibly lose activity at the elevated temperatures of certain industrial processing or large-scale AFP production. Using the small, thermolabile type III AFP as a model system, we demonstrate that AFP thermostability is dramatically enhanced via split intein-mediated N- and C-terminal end ligation. To engineer this circular protein, computational modeling and molecular dynamics simulations were applied to identify an extein sequence that would fill the 20-Å gap separating the free ends of the AFP, yet impose little impact on the structure and entropic properties of its ice-binding surface. The top candidate was then expressed in bacteria, and the circularized protein was isolated from the intein domains by ice-affinity purification. This circularized AFP induced bipyramidal ice crystals during ice growth in the hysteresis gap and retained 40% of this activity even after incubation at 100°C for 30 min. NMR analysis implicated enhanced thermostability or refolding capacity of this protein compared to the noncyclized wild-type AFP. These studies support protein backbone circularization as a means to expand the thermostability and practical applications of AFPs.
Margins of resection in surgical oncology are often a trade-off between decreasing cancer recurrence and preserving a patient’s aesthetic and function. The intelligent surgical knife (iKnife) aims to provide margins of resection in real-time leading to improved clinical outcomes while giving surgeons the confidence to excise tumors with smaller margins of resection. The iKnife utilizes mass spectrometry to identify the lipid and protein profiles of cells as they are cut with an electric cauterization tool. Through techniques such as multivariate analysis, proprietary software can discern healthy and cancerous tissue without the need for histological sectioning and staining. The effectiveness of the iKnife has been demonstrated ex vivo and in vivo with several types of tumors such as breast, ovarian, and colon cancer. The iKnife presents an exciting novel tool in the field of surgical oncology with the ability to provide an avenue to personalized medicine in the future.
Dans le jargon philosophique habituel, un jugement de type « universel » est un concept toujours valide dans toutes les situations / époques, qui s’applique à tous les individus qu’il a la prétention de catégoriser. Au cours de cet article, nous suggérons que l’ébauche d’une quelconque définition « universelle » de l’art doit se heurter à des problèmes ontologiques (l’essence de l’art) sérieux. Nous proposons qu’il soit plus prudent de s’abstenir de faire de tels jugements en ayant une approche fonctionnaliste pour décrire sans définir le processus créatif ainsi que les oeuvres qui y aboutissent. Nous faisons la démonstration de cette approche construite sur un refus conscient de définir l’art, en analysant (avec les catégories des fins et des moyens) le rapport à la technologie du pianiste Glenn Gould. Il s’agit, en quelque sorte, d’un dialogue ouvert avec le lecteur. Finalement, nous aboutissons à la conclusion qu’il peut être pertinent pour le chercheur-créateur (un mélange entre le théoricien et l’artiste qui cherche à valider son art) d’opter pour une esthétique singulière ou d’essayer de constituer une théorie universelle de l’art en attaquant le problème ontologique par le biais de la linguistique (une suggestion, sans garanties). En dehors de notre approche fonctionnaliste, qui par rigueur intellectuelle peut tendre vers un relativisme insatisfaisant, il s’agit des seuls choix prometteurs qui ne se limitent pas aux analyses historiques ou aux analyses d’oeuvres individuelles (le paradigme actuel de l’enseignement théorique universitaire en musique) auxquels nous avons pensé.In the usual philosophical jargon, a judgment qualified as “universal” is a concept valid at all times and in all contexts or periods, that apply to all individuals it intends to classify. In this article, I argue that any tentative “universal” definition of art is fraught with serious ontological problems (regarding its essence). I propose therefore that it would be more prudent to refrain from making such attempts, and to adopt instead a functional approach in describing, without defining, the creative processes, as well as the resulting musical works. I demonstrate this approach, which is built on a deliberate refusal to define art, by engaging in an open dialogue with the reader, analyzing (in terms of means and ends) how the pianist Glenn Gould related to technology. I conclude that it could be fruitful for the creator-searcher (the artist exploring the craft through theory) to choose a specific esthetics or to develop a universal theory of art through addressing the ontological problems with the help of linguistics (a suggestion with no guarantees). Indeed, apart from the functionalist approach, which may become unsatisfactory relativism, due to intellectual rigour, these avenues are the only promising ones that are not limited to historical or musical analyses of individual works (analyses that are the basis of the theoretical musical training in our universities)
The field of emergency medicine has changed since the first introduction of portable ultrasound fifty years ago. Smaller equipment and the ability to produce higher quality images has driven the wide adoption of Point-of-Care Ultrasound (PoCUS) in emergency departments. PoCUS is an integral tool for physicians to obtain images in real-time and rapidly diagnose critically ill patients for timely intervention when every minute matters. Recognizing Core applications of PoCUS has been highlighted by the Canadian Association of Emergency Physicians and training programs are within the core curriculum for EM residency. However, the main challenge of PoCUS is that the diagnostic accuracy and interpretability is dependent on operator expertise. With the resurgent interest in artificial intelligence (AI) in healthcare, its integration into PoCUS was promising. Several studies have looked at integrating AI analysis with PoCUS imaging to improve diagnostic accuracy, guide training models, and increase the accessibility of PoCUS for novice users. Given that PoCUS usage improves patient satisfaction and clinician confidence, increased PoCUS usage is a worthy and achievable goal in Canadian emergency departments. The promising adaptation of artificial intelligence with PoCUS assessments will serve to expand training and diagnostic confidence to improve patient outcomes.
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