Search

Enzymes, as natural and potentially long-term treatment options, have become one of the most sought-after pharmaceutical molecules to be delivered with nanoparticles (NPs); however, their instability during formulation often leads to underwhelming results. Various molecules, including the Tween® polysorbate series, have demonstrated enzyme activity protection but are often used uncontrolled without optimization. Here, poly(lactic-co-glycolic) acid (PLGA) NPs loaded with β-glucosidase (β-Glu) solutions containing Tween® 20, 60, or 80 were compared. Mixing the enzyme with Tween® pre-formulation had no effect on particle size or physical characteristics, but increased the amount of enzyme loaded. More importantly, NPs made with Tween® 20:enzyme solutions maintained significantly higher enzyme activity. Therefore, Tween® 20:enzyme solutions ranging from 60:1 to 2419:1 mol:mol were further analyzed. Isothermal titration calorimetry analysis demonstrated low affinity and unquantifiable binding between Tween® 20 and β-Glu. Incorporating these solutions in NPs showed no effect on size, zeta potential, or morphology. The amount of enzyme and Tween® 20 in the NPs was constant for all samples, but a trend towards higher activity with higher molar rapports of Tween® 20:β-Glu was observed. Finally, a burst release from NPs in the first hour with Tween®:β-Glu solutions was the same as free enzyme, but the enzyme remained active longer in solution. These results highlight the importance of stabilizers during NP formulation and how optimizing their use to stabilize an enzyme can help researchers design more efficient and effective enzyme loaded NPs.

Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized.

One of the key roles of National Aeronautics and Space Administration (NASA) is to help mitigate the risk and lower expenses associated with space exploration, science, and discovery to the point where industry and international partners are willing and able to profitably take on larger, more complex missions. To do this, the Agency must undertake a transformation to a more modern integrated Digital Engineering approach to mission definition and planning. This paper highlights NASA's journey in understanding what this Digital Engineering Transformation means for the Agency, the benefits of this transformation to human exploration definition and planning, and the benefits to the current Artemis campaign engineering capability portfolio. [ABSTRACT FROM AUTHOR]

Background While anxiety disorders are one of the most prevalent mental diseases, they are often overlooked due to shortcomings of the existing diagnostic procedures, which predominantly rely on self-reporting. Due to recent technological advances, this source of information could be complemented by the so-called observable cues – indicators that are displayed spontaneously through individuals’ physiological responses or behaviour and can be detected by modern devices. However, while there are several individual studies on such cues, this research area lacks a synthesis. In line with this, our scoping review aimed to identify observable cues that offer meaningful insight into individuals’ anxiety and to determine how these cues can be measured. Methods We followed the PRISMA guidelines for scoping reviews. The search string containing terms related to anxiety and observable cues was entered into four databases (Web of Science, MEDLINE, ERIC, IEEE). While the search – limited to English peer-reviewed records published from 2012 onwards – initially yielded 2311 records, only 33 articles fit our selection criteria and were included in the final synthesis. Results The scoping review unravelled various categories of observable cues of anxiety, specifically those related to facial expressions, speech and language, breathing, skin, heart, cognitive control, sleep, activity and motion, location data and smartphone use. Moreover, we identified various approaches for measuring these cues, including wearable devices, and analysing smartphone usage and social media activity. Conclusions Our scoping review points to several physiological and behavioural cues associated with anxiety and highlights how these can be measured. These novel insights may be helpful for healthcare practitioners and fuel future research and technology development. However, as many cues were investigated only in a single study, more evidence is needed to generalise these findings and implement them into practice with greater confidence.

This study reveals the influence of crystal orientation on formation of growth twins in magnetron-sputtered coatings. A comparison between materials with low and high stacking fault energy (SFE) was made: CoCrFeMnNi (25 mJ/m2) and Ni (125 mJ/m2). The coatings were grown on a polycrystalline 316L stainless-steel substrate with near-random crystal texture, providing a comprehensive selection of samples on a single substrate. Electron backscatter diffraction was used to identify the film orientation, followed by transmission electron microscopy of selected regions.The presence and density of twins depended on both the material and the growth orientation. For Ni, nanotwins were observed on

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

Abstract In this paper, we propose a novel approach for the kinematic calibration of collaborative redundat robots, focusing on improving their precision using a cost-effective and efficient method. We exploit the redundancy of the closed-loop kinematic chain by utilizing a spherical joint, enabling precise definition of the robot end-effector position while maintaining free joint motion in the null space. Leveraging the availability of joint torque sensors in most collaborative robots, we employ a kinesthetic approach to obtain constrained joint motion for calibration. An optimization approach is utilized to determine the optimal kinematic parameters based on measured joint positions and a constrained end-effector position defined by the spherical joint. The effectiveness of the proposed method is demonstrated and validated on the Franka Emika Panda robot, a 7-DoF robot. Results indicate a significant enhancement in absolute accuracy, with comparable performance to more expensive sensor systems such as optical measurement systems. Our approach offers a practical and cost-effective solution for improving the precision of collaborative robots.

U veljači 2021. Međunarodni je sud donio presudu u sporu između Katara i Ujedinjenih Arapskih Emirata o tumačenju Konvencije o ukidanju svih oblika rasne diskriminacije, koja je svojevrsni sudski epilog dugotrajnoga političkog sukoba zaljevskih država. Presuda Međunarodnog suda državljanstvu je odrekla značaj diskriminatorne osnove, što je u suprotnosti sa stavovima Odbora za ukidanje svih oblika rasne diskriminacije izraženima u takozvanim općim preporukama na Konvenciju. Takvo razilaženje u stavovima između Međunarodnog suda i Odbora otvara nekoliko širih pitanja. Prvo je od njih o pravnoj snazi i naravi općih preporuka konvencijskih tijela. Drugo je još šire pitanje o fragmentaciji međunarodnog prava kao procesu u kojem razilaženja u tumačenju konvencijskih tijela, međunarodnih i regionalnih sudova mogu imati važnu ulogu kao indikatori. Ovaj rad, s pomoću kontekstualizacije konkretnih pitanja postavljenih u postupku pred Međunarodnim sudom u sporu Katara i Ujedinjenih Arapskih Emirata razmatra navedena pitanja koja bitno određuju odnos suvremenoga međunarodnog prava i zaštite ljudskih prava kao njegovog dijela.

BackgroundThe motivational interviewing (MI) approach has been shown to help move ambivalent smokers toward the decision to quit smoking. There have been several attempts to broaden access to MI through text-based chatbots. These typically use scripted responses to client statements, but such nonspecific responses have been shown to reduce effectiveness. Recent advances in natural language processing provide a new way to create responses that are specific to a client’s statements, using a generative language model. ObjectiveThis study aimed to design, evolve, and measure the effectiveness of a chatbot system that can guide ambivalent people who smoke toward the decision to quit smoking with MI-style generative reflections. MethodsOver time, 4 different MI chatbot versions were evolved, and each version was tested with a separate group of ambivalent smokers. A total of 349 smokers were recruited through a web-based recruitment platform. The first chatbot version only asked questions without reflections on the answers. The second version asked the questions and provided reflections with an initial version of the reflection generator. The third version used an improved reflection generator, and the fourth version added extended interaction on some of the questions. Participants’ readiness to quit was measured before the conversation and 1 week later using an 11-point scale that measured 3 attributes related to smoking cessation: readiness, confidence, and importance. The number of quit attempts made in the week before the conversation and the week after was surveyed; in addition, participants rated the perceived empathy of the chatbot. The main body of the conversation consists of 5 scripted questions, responses from participants, and (for 3 of the 4 versions) generated reflections. A pretrained transformer-based neural network was fine-tuned on examples of high-quality reflections to generate MI reflections. ResultsThe increase in average confidence using the nongenerative version was 1.0 (SD 2.0; P=.001), whereas for the 3 generative versions, the increases ranged from 1.2 to 1.3 (SD 2.0-2.3; P

Controllable quantum many-body systems are platforms for fundamental investigations into the nature of entanglement and promise to deliver computational speed-up for a broad class of algorithms and simulations. In particular, engineering entanglement within a dense spin ensemble can turn it into a robust quantum memory or a computational platform. Recent experimental progress in dense central-spin systems motivates the design of algorithms that use a central-spin qubit as a convenient proxy for the ensemble. Here we propose a protocol that uses a central spin to initialize two dense spin ensembles into a pure antipolarized state and from there creates a many-body entangled state—a singlet—from the combined ensemble. We quantify the protocol performance for multiple material platforms and show that it can be implemented even in the presence of realistic levels of decoherence and diffusion. Our protocol introduces an algorithmic approach to the preparation of a known many-body state and to entanglement engineering in a dense spin ensemble, which can be extended towards a broad class of collective quantum states.

Mitral valve repair clip detachment and embolization is a rare phenomenon, with few reported cases. We describe a case of subacute transcatheter mitral valve repair clip embolization presenting as an inferior ST-segment elevation myocardial infarction, with subsequent successful percutaneous device retrieval. (Level of Difficulty: Intermediate.)

Summary: Enzymes catalyze biochemical reactions and play critical roles in human health and disease. Enzyme variants and deficiencies can lead to variable expression of glycans, which can affect physiology, influence predilection for disease, and/or directly contribute to disease pathogenesis. Although certain well-characterized enzyme deficiencies result in overt disease, some of the most common enzyme deficiencies in humans form the basis of blood groups. These carbohydrate blood groups impact fundamental areas of clinical medicine, including the risk of infection and severity of infectious disease, bleeding risk, transfusion medicine, and tissue/organ transplantation. In this review, we examine the enzymes responsible for carbohydrate-based blood group antigen biosynthesis and their expression within the human population. We also consider the evolutionary selective pressures, e.g. malaria, that may account for the variation in carbohydrate structures and the implications of this biology for human disease.