Mixed Protein Carriers for Modulating DNA Release

Aqueous mixtures of oppositely charged polyelectrolytes undergo associative phase separation, resulting in coacervation, gelation, or precipitation. This phenomenon has been exploited in forming DNA gel particles by interfacial diffusion. We report here the formation of DNA gel particles by mixing solutions of double-stranded DNA with aqueous solutions containing two cationic proteins, lysozyme and protamine sulfate. The effect of the lysozyme/protamine ratio on the degree of DNA entrapment, surface morphology, swelling−deswelling behavior, and kinetics of DNA release has been investigated. By mixing the two proteins, we obtain particles that display higher loading efficiency and loading capacity values, in comparison to those obtained in single-protein systems. Examination of the release profiles has shown that in mixed protein particles, complex, dual-stage release kinetics is obtained. The overall release profile is dependent on the lysozyme/protamine ratio. The obtained profiles, or segments of them, are accuratelly fitted using the zero-order and first-order models, and the Weibull function. Fluorescence microscopy studies have suggested that the formation of these particles is associated with the conservation of the secondary structure of DNA. This study presents a new platform for controlled release of DNA from DNA gel particles formed by interfacial diffusion

Polyion Adsorption onto Catanionic Surfaces. A Monte Carlo Study

The adsorption of a single and negatively charged polyion with varying flexibility onto a surface carrying both negative and positive charges representing a charged membrane surface has been investigated by using a simple model employing Monte Carlo simulations. The polyion was represented by a sequence of negatively charged hard spheres connected with harmonic bonds. The charged surface groups were also represented by charged hard spheres, and they were positioned on a hard surface slightly protruding into the solution. The surface charges were either frozen in a liquidlike structure or laterally mobile. With a large excess of positive surface charges, the classical picture of a strongly adsorbed polyion with an extended and flat configuration emerged. However, adsorption also appeared at a net neutral surface or at a weakly negatively charged surface, and at these conditions the adsorption was stronger with a flexible polyion as compared to a semiflexible one, two features not appearing in simpler models containing homogeneously charged surfaces. The presence of charged surface patches (frozen surface charges) and the ability of polarization of the surface charges (mobile surface charges) are the main reasons for the enhanced adsorption. The stronger adsorption with the flexible chain is caused by its greater ability to spatially correlate with the surface charges

BPS partition functions in N = 4 Yang-Mills theory on T^4

We consider N = 4 Yang-Mills theory on a flat four-torus with the R-symmetry current coupled to a flat background connection. The partition function depends on the coupling constant of the theory, but when it is expanded in a power series in the R-symmetry connection around the loci at which one of the supersymmetries is unbroken, the constant and linear terms are in fact independent of the coupling constant and can be computed at weak coupling for all non-trivial 't Hooft fluxes. The case of a trivial 't Hooft flux is difficult because of infrared problems, but the corresponding terms in the partition function are uniquely determined by S-duality.Comment: 23 pages, v2 Minor correction

National Institutes of Health Career Development Awards for Cardiovascular Physician-Scientists: Recent Trends and Strategies for Success

Nurturing the development of cardiovascular physician-scientist investigators is critical for sustained progress in cardiovascular science and improving human health. The transition from an inexperienced trainee to an independent physician-scientist is a multifaceted process requiring a sustained commitment from the trainee, mentors, and institution. A cornerstone of this training process is a career development (K) award from the National Institutes of Health (NIH). These awards generally require 75% of the awardee's professional effort devoted to research aims and diverse career development activities carried out in a mentored environment over a 5-year period. We report on recent success rates for obtaining NIH K awards, provide strategies for preparing a successful application and navigating the early career period for aspiring cardiovascular investigators, and offer cardiovascular division leadership perspectives regarding K awards in the current era. Our objective is to offer practical advice that will equip trainees considering an investigator path for success

C3-Cloud personalised care plan development platform for addressing the needs of multi-morbidity and managing poly-pharmacy : protocol for a pilot technology trial

Background: There is an increasing need to organise the care around the patient and not the disease, as well as taking into account the complex realities of multiple physical, psycho-social conditions and polypharmacy. Integrated patient-centred care delivery platforms have been developed for both patients and clinicians. These platforms could provide a promising way to achieve a collaborative environment that improves the provision of integrated care for patients via enhanced ICT solutions. Objective: The C3-Cloud project has developed two collaborative computer platforms for patients and members of the Multi-Disciplinary Team and deployed these in three different European settings. The objective of this study is to pilot test the platforms and evaluate their impact on patients, informal caregivers, healthcare professionals and, in extend, healthcare systems. Methods: This paper describes the protocol for conducting an evaluation of the user-centred design, user experience, acceptability, and usefulness of the platforms. For this, four ‘testing and evaluation’ phases have been defined, involving multiple qualitative methods, and advanced impact modelling. Results: The technology trial in this 4-year funded project (2016-2020) is currently in its execution phase. The testing and evaluation phase 1 and 2 have been completed with satisfying results on system component tests, and promising results on application and usability tests. The pilot technology trial for evaluation phase 3 and 4 was launched in August 2019. Data collection for these phases is underway and results are forthcoming, approximately in April 2020. We believe that the phased, iterative approach taken is useful as it involves relevant stakeholders at crucial stages in the platform development and allows for a sound user acceptance assessment of the final product. Conclusions: Patients with multiple chronic conditions often experience shortcomings in the care they receive. It is hoped that personalised care plan platforms for patients and collaboration platforms for members of Multi-Disciplinary Teams can help to tackle the specific challenges of clinical guideline reconciliation for multimorbid patients and improved the management of poly-pharmacy. The initial evaluative phases have indicated promising results of platform usability. The phased methodology has shown useful results in the first two phases, while results of phase 3 and 4 are pending. Clinical Trial: https://www.clinicaltrials.gov/ct2/show/NCT0383420

Locust: C++ software for simulation of RF detection

The Locust simulation package is a newC++software tool developed to simulate the measurement of time-varying electromagnetic fields using RF detection techniques. Modularity and flexibility allow for arbitrary input signals, while concurrently supporting tight integration with physics-based simulations as input. External signals driven by the Kassiopeia particle tracking package are discussed, demonstrating conditional feedback between Locust and Kassiopeia during software execution. An application of the simulation to the Project8 experiment is described

Cyclotron radiation emission spectroscopy signal classification with machine learning in project 8

The cyclotron radiation emission spectroscopy (CRES) technique pioneered by Project 8measures electromagnetic radiation fromindividual electrons gyrating in a backgroundmagnetic field to construct a highly precise energy spectrumfor beta decay studies and other applications. The detector,magnetic trap geometry and electron dynamics give rise to amultitude of complex electron signal structures which carry information about distinguishing physical traits.Withmachine learningmodels, we develop a scheme based on these traits to analyze and classifyCRES signals. Proper understanding and use of these traits will be instrumental to improve cyclotron frequency reconstruction and boost the potential of Project 8 to achieveworld-leading sensitivity on the tritiumendpointmeasurement in the future