Mechanisms Underlying Connexin Hemichannel Activation in Disease

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.     

Efficient symmetry breaking formulations for the job grouping problem

The job grouping problem consists of assigning a set of jobs, each with a specific set of tool requirements, to machines with a limited tool capacity in order to minimize the number of machines needed. Traditionally, a formulation has been used that assigns jobs to machines. However, such a formulation contains a lot of symmetry since the machines are identical and they can be permuted in any feasible solution. We propose a new formulation for this problem, based on the asymmetric representatives formulation (ARF) idea. This formulation eliminates the symmetry between the identical machines. We further propose various symmetry breaking constraints, including variable reduction and lexicographic ordering constraints, which can be added to the traditional formulation. These formulations are tested on a data set from the literature and newly generated data sets using a state-of-the-art commercial solver, which includes symmetry breaking features.     

Unnormalized and normalized forms of gefura measures in directed and undirected networks

In some networks nodes belong to predefined groups(e.g.,authors belong to institutions).Common network centrality measures do not take this structure into account.Gefura measures are designed as indicators of a node’s brokerage role between such groups.They are defined as variants of betweenness centrality and consider to what extent a node belongs to shortest paths between nodes from different groups.In this article we make the following new contributions to their study:(1) We systematically study unnormalized gefura measures and show that,next to the ‘structural’ normalization that has hitherto been applied,a ‘basic’ normalization procedure is possible.While the former normalizes at the level of groups,the latter normalizes at the level of nodes.(2) Treating undirected networks as equivalent to symmetric directed networks,we expand the definition of gefura measures to the directed case.(3) It is shown how Brandes’ algorithm for betweenness centrality can be adjusted to cover these cases.     

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− and C57BL/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+/− mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.     

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury

A simple and sensitive method for analysis of three tetracyclic antidepressants, maprotiline, mianserin, and setiptiline, in human whole blood was developed using headspace-solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). A vial containing a blood sample, sodium hydroxide, and imipramine as an internal standard was heated at 120 degrees C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds absorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.005 to 5.0 microg/g for mianserin and setiptiline and from 0.025 to 25 microg/g for maprotiline. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a medicolegal case in which the cause of death was suspected to be acute setiptiline poisoning. Setiptiline was detected in the left and right heart blood samples of the victim at concentrations of 1.77 and 0.78 microg/g, respectively.     

Body potential analysis of ultra thin gate oxide FD-SOI MOSFETs in accumulation mode operation

A new method for body potential estimation of ultra thin gate oxide fully-depleted silicon-on-insulator MOSFETs in accumulation mode operation is presented. The impact of the back gate voltage, gate length and drain voltage on the body potential is investigated. The magnitude of the Electron Valence Band gate tunneling-induced 2nd peak of the transconductance, characteristic of these ultra thin gate oxide FD SOI MOSFETs, is analyzed in terms of body potential changes and front gate characteristics shifts. Finally, a decrease of the body potential for strong accumulation back gate biases is revealed and discussed.     

An industrial extension of the discrete lot-sizing and scheduling problem

We propose a model and solution algorithm for an industrial production planning problem at Solideal, an international tire manufacturer. The tires are built in molds and are produced in heaters in large series production runs. Some tires can be cured in two different types of heaters with different efficiencies. Preparing a heater and mold for a specific tire type requires a start up. The resulting lot-sizing problem is an extension of the standard Discrete Lot-Sizing and Scheduling Problem. The specific extensions which complicate the problem are: (i) general start-up times, which can be a fraction of the time bucket; (ii) multiple alternative machines with different efficiencies; (iii) multiple capacitated resources, namely the molds and heaters; and (iv) backlogging. These issues are directly motivated by our real life production planning problem. We propose a column-generation-based algorithm for this problem. The dynamic programming recursion for the subproblem is substantially improved by using valid bounds on the state space and cost function. Further, Lagrange relaxation is used to reduce the degeneracy of the master problem. We test our algorithm on real life data sets with up to 30 products and 30 periods and find good quality solutions and lower bounds within a reasonable computation time. Our best implementation has an overall average gap of 0.25% on these test problems.     

CFD simulation and experimental validation of fluid flow and particle transport in a model of alveolated airways

Accurate modeling of air flow and aerosol transport in the alveolated airways is essential for quantitative predictions of pulmonary aerosol deposition. However, experimental validation of such modeling studies has been scarce. The objective of this study is to validate computational fluid dynamics (CFD) predictions of flow field and particle trajectory with experiments within a scaled-up model of alveolated airways. Steady flow (Re=0.13) of silicone oil was captured by particle image velocimetry (PIV), and the trajectories of 0.5 and 1.2 mm spherical iron beads (representing 0.7–14.6 μm aerosol in vivo) were obtained by particle tracking velocimetry (PTV). At 12 selected cross sections, the velocity profiles obtained by CFD matched well with those by PIV (within 1.7% on average). The CFD predicted trajectories also matched well with PTV experiments. These results showed that air flow and aerosol transport in models of human alveolated airways can be simulated by CFD techniques with reasonable accuracy.     

Fenton peroxidation improves the drying performance of waste activated sludge

Advanced sludge treatment processes (AST) reduce the amount of sludge produced and improve the dewaterability, thus probably also affecting the heat transfer properties and the drying characteristics of the sludge. This paper studies the influence of the Fenton peroxidation on the thermal conductivity of the sludge. Results demonstrate that the Fenton's peroxidation positively influences the sludge cake consistency and hence enhances the mechanical dewaterability and the drying characteristics of the dewatered sludge. For the two sludges used in this study, i.e. obtained from the wastewater treatment plants (WWTP) of Tienen and Sint-Niklaas--the dry solids content of the mechanically dewatered sludge increased from 22.5% to 40.3% and from 18.7% to 35.2%, respectively. The effective thermal conductivity k(e) of the untreated and the peroxidized sludges is measured and used to determine the heat transfer coefficient h(s). An average improvement for k(e) of 16.7% (Tienen) and 5.8% (Sint-Niklaas) was observed. Consequently the value of h(s) increased with 15.6% (Tienen) and 5.0% (Sint-Niklaas). This increased heat transfer coefficient in combination with the increased dewaterability has direct implications on the design of sludge dryers. A plate-to-plate calculation of a multiple hearth dryer illustrates that the number of plates required to dry the peroxidized sludge to 90% DS is less than half the number of plates needed to dry untreated sludge. This results in reduced dryer dimensions or a higher capacity for an existing dryer of given dimensions.