Chaotic Dynamics of a Free Particle Interacting Linearly with a Harmonic Oscillator

We study the closed Hamiltonian dynamics of a free particle moving on a ring, over one section of which it interacts linearly with a single harmonic oscillator. On the basis of numerical and analytical evidence, we conjecture that at small positive energies the phase space of our model is completely chaotic except for a single region of complete integrability with a smooth sharp boundary showing no KAM-type structures of any kind. This results in the cleanest mixed phase space structure possible, in which motions in the integrable region and in the chaotic region are clearly separated and independent of one another. For certain system parameters, this mixed phase space structure can be tuned to make either of the two components disappear, leaving a completely integrable or completely chaotic phase space. For other values of the system parameters, additional structures appear, such as KAM-like elliptic islands, and one parameter families of parabolic periodic orbits embedded in the chaotic sea. The latter are analogous to bouncing ball orbits seen in the stadium billiard. The analytical part of our study proceeds from a geometric description of the dynamics, and shows it to be equivalent to a linked twist map on the union of two intersecting disks.Comment: 17 pages, 11 figures Typos corrected to display section label

Biophysics in drug discovery : impact, challenges and opportunities

Over the past 25 years, biophysical technologies such as X-ray crystallography, nuclear magnetic resonance spectroscopy, surface plasmon resonance spectroscopy and isothermal titration calorimetry have become key components of drug discovery platforms in many pharmaceutical companies and academic laboratories. There have been great improvements in the speed, sensitivity and range of possible measurements, providing high-resolution mechanistic, kinetic, thermodynamic and structural information on compound-target interactions. This Review provides a framework to understand this evolution by describing the key biophysical methods, the information they can provide and the ways in which they can be applied at different stages of the drug discovery process. We also discuss the challenges for current technologies and future opportunities to use biophysical methods to solve drug discovery problems

Diagnostic Potential of Imaging Flow Cytometry

Imaging flow cytometry (IFC) captures multichannel images of hundreds of thousands of single cells within minutes. IFC is seeing a paradigm shift from low- to high-information-content analysis, driven partly by deep learning algorithms. We predict a wealth of applications with potential translation into clinical practice

Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors

<p>Abstract</p> <p>Background</p> <p>We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.</p> <p>Results</p> <p>Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.</p> <p>Conclusion</p> <p>The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.</p

Efficacy and safety of N-acetyl-l-leucine in Niemann–Pick disease type C

Objective: To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. Methods: In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. Results: 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. Conclusions: NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. Gov identifier: NCT03759639

Alfabetización informacional en la educación superior virtual: logros y desafíos.

Virtual education has become an alternative for students to access the higher education system. In Colombia, there has been an increase in the number of undergraduate programs in this form of education. However, information about the pedagogical work undertaken in those programs is scarce, and it is needed to examine their quality. This research project examined the education community’s perception of undergraduate virtual education programs in Colombian higher education institutions. One of the key elements in the analysis was the development of students’ information literacy to find out about possible ruptures, transformations, advantages, problems and solutions that emerge from this form of education. The study used a quantitative and qualitative approach to gather information from teachers, coordinators, tutors and students from 9 higher education institutions. Results show that efforts to improve students’ information literacy have been undertaken; however a greater collective effort is needed to improve the search for, evaluation and ethical use of information. Implicit here is the need for expert training and the need to reflect upon strategies to combat plagiarism.La educación virtual se constituye en una alternativa para el acceso de un mayor número de estudiantes al sistema de educación superior. En Colombia se ha incrementado el número de programas de pregrado en esta modalidad, pero la documentación sobre el trabajo pedagógico desarrollado en la implementación de estas propuestas educativas es insuficiente para examinar su calidad. Esta investigación propuso como una de sus categorías de análisis indagar las percepciones y experiencias de agentes educativos acerca del desarrollo de la alfabetización informacional en los programas que se ofrecen en esa modalidad para especificar transformaciones, avances, rupturas, entre otros aspectos. El estudio empleó técnicas cuantitativas y cualitativas para la recolección de información de profesores, coordinadores, tutores y estudiantes de nueve instituciones de educación superior que contaban con programas con un alto componente virtual. Los resultados muestran que se ha dado inicio al fortalecimiento de las competencias informacionales de los estudiantes, pero que aún se requiere del trabajo colectivo entre profesores, tutores y estudiantes para refinar los criterios de búsqueda, valoración y aplicación de la información. Se evidencia también la necesidad de capacitación para expertos temáticos y la necesidad de reflexionar sobre estrategias para combatir el plagio