MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.     

Incremental semantic analysis for OCL compilers

In software engineering, modeling with unified modeling language and object constraint language became industry standards and are supported by many computer-aided software engineering tools. The increasing number of the modeled functionalities results in complex models that need more and more textual constraints to express the hidden restrictions applied to the systems. During the metamodel development, rebuilding all the constraints is unnecessary when only a few changes have been applied due to the iterative, incremental manner of modifications. In this paper, we present a family of algorithms that handles the changes in constraints incrementally on the expression level; thus, the required rebuilds are kept to a minimum. Incremental variable reference resolving and type checking are performed as a part of the incremental semantic analysis. Balancing between the incremental and standard compilation is also considered, heuristics are given to select the faster method of compilation at each iteration. With the achieved results the duration of metamodel development can be decreased; thus, the efficiency of the environment is improved.     

Collective foraging in heterogeneous landscapes

Animals foraging alone are hypothesized to optimize the encounter rates with resources through Lévy walks. However, the issue of how the interactions between multiple foragers influence their search efficiency is still not completely understood. To address this, we consider a model to study the optimal strategy for a group of foragers searching for targets distributed heterogeneously. In our model, foragers move on a square lattice containing immobile but regenerative targets. At any instant, a forager is able to detect only those targets that happen to be in the same site. However, we allow the foragers to have information about the state of other foragers. A forager who has not detected any target walks towards the nearest location, where another forager has detected a target, with a probability exp(−αd), where d is the distance between the foragers and α is a parameter characterizing the propensity of the foragers to aggregate. The model reveals that neither overcrowding (α → 0) nor independent searching (α → ∞) is beneficial for the foragers. For a patchy distribution of targets, the efficiency is maximum for intermediate values of α. In addition, in the limit α → 0, the length of the walks can become scale-free.     

Thermal analysis of 9977 radioactive material package

The 9977 package is a certified type B transportation packaging that was designed to transport radioactive materials with a decay heat load of up to 19?W. The packaging was recently modified to accommodate increased content heat load (up to 38?W) by employing an aluminium heat dissipating sleeve outside the containment vessel (CV), as well as an aluminium spacer inside the CV holding two 3013 containers. This paper provides highlights of thermal analyses of the modified 9977 package that were performed to evaluate its compliance with the 10 CFR 71 regulatory safety requirements. Parametric studies were also performed to examine effects of (i) surface properties, e.g. light absorptivity and emissivity, of the packaging; (ii) total decay heat loads, ranging from 18 to 38?W; and (iii) distribution of decay heat load inside the CV on the temperature of the Viton O-ring seal. The results of thermal analyses show that for the normal condition of transport with insolation, increasing absorptivity and decreasing emissivity increase the temperature of the O-ring; decreasing heat load decreases the temperature of the O-ring, whereas changing heat load distribution has little effect on the temperature of the O-ring. Likewise, changing the thermal conductivity of the spacer inside the CVhas little effect on the temperature of the O-ring. Briefly discussed is the possible extension of the annual maintenance interval of the 9977 package, based on previous work and the data obtained in the long-term leak performance tests conducted by the Savannah River National Laboratory.     

Modeling heterogeneous bacterial populations exposed to antibiotics: The logistic‐dynamics case

In typical in vitro tests for clinical use or development of antibiotics, samples from a bacterial population are exposed to an antibiotic at various concentrations. The resulting data can then be used to build a mathematical model suitable for dosing regimen design or for further development. For bacterial populations that include resistant subpopulations—an issue that has reached alarming proportions—building such a model is challenging. In prior work, we developed a related modeling framework for such heterogeneous bacterial populations following linear dynamics when exposed to an antibiotic. We extend this framework to the case of logistic dynamics, common among strongly resistant bacterial strains. Explicit formulas are developed that can be easily used in parameter estimation and subsequent dosing regimen design under realistic pharmacokinetic conditions. A case study using experimental data from the effect of an antibiotic on a gram‐negative bacterial population exemplifies the usefulness of the proposed approach. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2385–2393, 2015     

Deformation and Fracture of β‐Silicon Nitride Micropillars

Room‐temperature deformation and fracture behaviors under microcompression of single crystal β‐silicon nitride (Si₃N₄) micropillars were investigated. Pillars were fabricated by focused ion beam (FIB) in large Si₃N₄ grains, located close to the basal and prismatic orientations, selected by electron backscatter diffraction (EBSD). The micromechanical test and the damage characterization were performed by nanoindentation and scanning electron microscopy (SEM), respectively. The elastic, plastic, and fracture properties, such as Young's modulus, yield stress, and rupture stress are considerably influenced by the pillar orientation. The activation of the type slip system was identified in case of basal oriented micropillars.