Current Perspectives on Synthetic Compartments for Biomedical Applications

Nano- and micrometer-sized compartments composed of synthetic polymers are designed to mimic spatial and temporal divisions found in nature. Self-assembly of polymers into compartments such as polymersomes, giant unilamellar vesicles (GUVs), layer-by-layer (LbL) capsules, capsosomes, or polyion complex vesicles (PICsomes) allows for the separation of defined environments from the exterior. These compartments can be further engineered through the incorporation of (bio)molecules within the lumen or into the membrane, while the membrane can be decorated with functional moieties to produce catalytic compartments with defined structures and functions. Nanometer-sized compartments are used for imaging, theranostic, and therapeutic applications as a more mechanically stable alternative to liposomes, and through the encapsulation of catalytic molecules, i.e., enzymes, catalytic compartments can localize and act in vivo. On the micrometer scale, such biohybrid systems are used to encapsulate model proteins and form multicompartmentalized structures through the combination of multiple compartments, reaching closer to the creation of artificial organelles and cells. Significant progress in therapeutic applications and modeling strategies has been achieved through both the creation of polymers with tailored properties and functionalizations and novel techniques for their assembly

What is the evidence for giving chemoprophylaxis to children or students attending the same preschool, school or college as a case of meningococcal disease?

We performed a systematic literature review to assess the effectiveness of chemoprophylaxis for contacts of sporadic cases of invasive meningococcal disease (IMD) in educational settings. No studies directly compared IMD risk in contacts with/without chemoprophylaxis. However, compared to the background incidence, an elevated IMD risk was identified in settings without a general recommendation for chemoprophylaxis in pre-schools [pooled risk difference (RD) 58·2/10⁵, 95% confidence interval (CI) 27·3-89·0] and primary schools (pooled RD 4·9/10⁵, 95% CI 2·9-6·9) in the ~30 days after contact with a sporadic IMD case, but not in other educational settings. Thus, limited but consistent evidence suggests the risk of IMD in pre-school contacts of sporadic IMD cases is significantly increased above the background risk, but lower than in household contacts (pooled RD for household contacts with no chemoprophylaxis vs. background incidence: 480·1/10⁵, 95% CI 321·5-639·9). We recommend chemoprophylaxis for pre-school contacts depending on an assessment of duration and closeness of contact

Anisotropic Local Stress and Particle Hopping in a Deeply Supercooled Liquid

The origin of the microscopic motions that lead to stress relaxation in deeply supercooled liquid remains unclear. We show that in such a liquid the stress relaxation is locally anisotropic which can serve as the driving force for the hopping of the system on its free energy surface. However, not all hopping are equally effective in relaxing the local stress, suggesting that diffusion can decouple from viscosity even at local level. On the other hand, orientational relaxation is found to be always coupled to stress relaxation.Comment: 4 pages, 3 figure

Transverse thermal depinning and nonlinear sliding friction of an adsorbed monolayer

We study the response of an adsorbed monolayer under a driving force as a model of sliding friction phenomena between two crystalline surfaces with a boundary lubrication layer. Using Langevin-dynamics simulation, we determine the nonlinear response in the direction transverse to a high symmetry direction along which the layer is already sliding. We find that below a finite transition temperature, there exist a critical depinning force and hysteresis effects in the transverse response in the dynamical state when the adlayer is sliding smoothly along the longitudinal direction.Comment: 4 pages, 4 figures, to appear in Phys. Rev. Let

Nonlinear sliding friction of adsorbed overlayers on disordered substrates

We study the response of an adsorbed monolayer on a disordered substrate under a driving force using Brownian molecular-dynamics simulation. We find that the sharp longitudinal and transverse depinning transitions with hysteresis still persist in the presence of weak disorder. However, the transitions are smeared out in the strong disorder limit. The theoretical results here provide a natural explanation for the recent data for the depinning transition of Kr films on gold substrate.Comment: 8 pages, 8 figs, to appear in Phys. Rev.

Boundary lubrication properties of materials with expansive freezing

We have performed molecular dynamics simulations of solid-solid contacts lubricated by a model fluid displaying many of the properties of water, particularly its expansive freezing. Near the region where expansive freezing occurs, the lubricating film remains fluid, and the friction force decreases linearly as the shear velocity is reduced. No sign of stick-slip motion is observed even at the lowest velocities. We give a simple interpretation of these results, and suggest that in general good boundary lubrication properties will be found in the family of materials with expansive freezing.Comment: Version to appear in Phys. Rev. Let

30 years of collaboration

We highlight some of the most important cornerstones of the long standing and very fruitful collaboration of the Austrian Diophantine Number Theory research group and the Number Theory and Cryptography School of Debrecen. However, we do not plan to be complete in any sense but give some interesting data and selected results that we find particularly nice. At the end we focus on two topics in more details, namely a problem that origins from a conjecture of Rényi and Erdős (on the number of terms of the square of a polynomial) and another one that origins from a question of Zelinsky (on the unit sum number problem). This paper evolved from a plenary invited talk that the authors gaveat the Joint Austrian-Hungarian Mathematical Conference 2015, August 25-27, 2015 in Győr (Hungary)

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Integration of genetic and genomics resources in einkorn wheat enables precision mapping of important traits

Einkorn wheat (Triticum monococcum) is an ancient grain crop and a close relative of the diploid progenitor (T. urartu) of polyploid wheat. It is the only diploid wheat species having both domesticated and wild forms and therefore provides an excellent system to identify domestication genes and genes for traits of interest to utilize in wheat improvement. Here, we leverage genomic advancements for einkorn wheat using an einkorn reference genome assembly combined with skim-sequencing of a large genetic population of 812 recombinant inbred lines (RILs) developed from a cross between a wild and a domesticated T. monococcum accession. We identify 15,919 crossover breakpoints delimited to a median and average interval of 114 Kbp and 219 Kbp, respectively. This high-resolution mapping resource enables us to perform fine-scale mapping of one qualitative (red coleoptile) and one quantitative (spikelet number per spike) trait, resulting in the identification of small physical intervals (400 Kb to 700 Kb) with a limited number of candidate genes. Furthermore, an important domestication locus for brittle rachis is also identified on chromosome 7A. This resource presents an exciting route to perform trait discovery in diploid wheat for agronomically important traits and their further deployment in einkorn as well as tetraploid pasta wheat and hexaploid bread wheat cultivars