Tumor Necrosis Factor-α Induces a Preeclamptic-like Phenotype in Placental Villi via Sphingosine Kinase 1 Activation

Preeclampsia (PE) involves inadequate placental function. This can occur due to elevated pro-inflammatory tumor necrosis factor-α (TNF-α). In other tissues, TNF-α signals via sphingosine kinase 1 (SphK1). SphK1 hinders syncytial formation. Whether this occurs downstream of TNF-α signaling is unclear. We hypothesized that placental SphK1 levels are higher in PE and elevated TNF-α decreases syncytial function, increases syncytial shedding, and increases cytokine/factor release via SphK1 activity. Term placental biopsies were analyzed for SphK1 using immunofluorescence and qRT-PCR. Term placental explants were treated after 4 days of culture, at the start of syncytial regeneration, with TNF-α and/or SphK1 inhibitors, PF-543. Syncytialization was assessed by measuring fusion and chorionic gonadotropin release. Cell death and shedding were measured by lactate dehydrogenase release and placental alkaline phosphatase-positive shed particles. Forty-two cytokines were measured using multiplex assays. Placental SphK1 was increased in PE. Increased cell death, shedding, interferon-α2, IFN-γ-induced protein 10, fibroblast growth factor 2, and platelet-derived growth factor-AA release induced by TNF-α were reversed upon SphK1 inhibition. TNF-α increased the release of 26 cytokines independently of SphK1. TNF-α decreased IL-10 release and inhibiting SphK1 reversed this effect. Inhibiting SphK1 alone decreased TNF-α release. Hence, SphK1 partially mediates the TNF-α-induced PE placental phenotype, primarily through cell damage, shedding, and specific cytokine release.     

The effect of depth and duration of UV radiation on polypropylene modification via photoinitiation

Linear polypropylene (PP) was modified using UV radiation in the presence of 0.5 wt % of benzophenone photoinitiator to introduce long chain branching (LCB) to the PP backbone. Irradiation was carried out in the solid state and the temperature level was kept below 60°C. The effects of radiation duration and sample thickness on the extent of these branching modification reactions were investigated. Viscoelastic properties, molecular weight, molecular weight distribution, and gel content were determined and compared for runs having different sample thicknesses, irradiated for different times. Comparisons were also conducted with the parent PP and the PP mixed with photoinitiator. It was found that LCB decreased by increasing the thickness of the samples. Conversely, an increase in radiation duration resulted in enhanced LCB but also led to larger gel content in the samples. Based on all these measurements and observations, a mechanism was suggested to explain formation of long chain branches (LCBs) in PP in the solid state via photoinitiation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41021.     

Analysis of heart rate dynamics based on nonlinear lagged returned map for sudden cardiac death prediction in cardiovascular patients

Multidimensional Systems and Signal Processing - Sudden cardiac death (SCD) generally applied to an unpredicted death from a cardiovascular cause in a subject with or without preexisting heart...     

3D numerical study of induced-charge electrokinetic motion of heterogeneous particle in a microchannel

The transient induced-charge electrophoretic (ICEP) motion of a Janus particle in a microchannel is numerically simulated with a complete 3D multi-physics model in this paper. A half of the Janus particle is an ideally polarizable material, the other half is a dielectric material. The distribution of induced surface charge varies on the ideally polarizable hemisphere of the Janus particle. Under an externally applied electric field, these surface charges generate micro vortices in the liquid. The numerical results illustrate that the orientation of Janus particle determines the direction of particle's motion and affects the velocity of the particle. The vortices on the polarizable side of the Janus particle act like an engine and push the particle to move faster in comparison with non-polarizable particles or fully polarizable particles. The bigger Janus particles move faster than the smaller ones. In the current paper, effects of the applied electric field, size of the particle, zeta potential of the non-polarizable part on the motion of Janus particle are also studied.     

Genetic Dominant Variants in STUB1, Segregating in Families with SCA48, Display In Vitro Functional Impairments Indistinctive from Recessive Variants Associated with SCAR16

Variants in STUB1 cause both autosomal recessive (SCAR16) and dominant (SCA48) spinocerebellar ataxia. Reports from 18 STUB1 variants causing SCA48 show that the clinical picture includes later-onset ataxia with a cerebellar cognitive affective syndrome and varying clinical overlap with SCAR16. However, little is known about the molecular properties of dominant STUB1 variants. Here, we describe three SCA48 families with novel, dominantly inherited STUB1 variants (p.Arg51_Ile53delinsProAla, p.Lys143_Trp147del, and p.Gly249Val). All the patients developed symptoms from 30 years of age or later, all had cerebellar atrophy, and 4 had cognitive/psychiatric phenotypes. Investigation of the structural and functional consequences of the recombinant C-terminus of HSC70-interacting protein (CHIP) variants was performed in vitro using ubiquitin ligase activity assay, circular dichroism assay and native polyacrylamide gel electrophoresis. These studies revealed that dominantly and recessively inherited STUB1 variants showed similar biochemical defects, including impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP. Our findings expand the molecular understanding of SCA48 but also mean that assumptions concerning unaffected carriers of recessive STUB1 variants in SCAR16 families must be re-evaluated. More investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases.     

Evaluation of air flow resistance across a green fig bed for selecting an appropriate pressure drop prediction equation

In this study the physical properties of green fig (Ficus carica L.) at different moisture contents were measured. Pressure drop across a bed of green fig was also evaluated. The moisture content and air flow ranges used in this study were 5.74-34.08% (db) and 0.2-1.1 (m³ s⁻¹ m⁻²), respectively. To measure resistance to air flow an appropriate test rig was designed and fabricated. A thick bed of seven depths of loose and random filling of fig bed were envisaged (5, 10, …, 35 cm). Principle dimensions, geometric mean diameter, sphericity, roughness factor of fig kernels and bulk density increased with an increase in moisture content, whereas kernel density and porosity decreased with an increase in fig moisture content. The air flow resistance across the bed increased with an increase in bed depth and moisture content. The modified Ergun model with higher values for coefficient of determination, lower values for root mean square error and mean relative deviation modulus was the best model for predicting pressure drop across green figs bed for the conditions studied.     

Optimization of Pump Scheduling Program in Water Supply Systems Using a Self-Adaptive NSGA-II; a Review of Theory to Real Application

The operation of pumps imposes significant costs on a water distribution system for energy supply and pumps maintenance. To derive an optimum pumps scheduling program, this study presents a multiobjective optimization problem with the objective functions of 1- energy cost and 2- the number of pump switches. The optimization of both objective functions together leads to a multiobjective constrained optimization problem. To solve the problem, the Non-Dominated Sorting Genetic Algorithm, version II, (NSGA-II) is coupled to the EPANET hydraulic simulation model. For constraint handling, some modifications are introduced to the standard NSGA-II to make it self-adaptive through which all constraints of the problem are automatically satisfied. Application of the model to a test example and a real pipe network verifies that the proposed scheme is computationally efficient and reliable. Also, optimization of the real pipe network reveals that by a careful pump scheduling program the total number of pump switches even in optimum operations could be decreased by 69% while the energy cost increases at most by 10%.     

Fluid physics around conductive deformable flaps within an induced-charge electrokinetically driven microsystem

The induced-charge electrokinetic motion of a conductive deformable flap (which is installed on the walls of a microchannel) is numerically studied in this article. The relationship between the flap orientation (i.e., vertical, horizontal and oblique positions) and its motion is studied. Stagnation point concept is used to explain the behavior of the flap at different situations. The stagnation point is defined as a point on the flap surface where the induced zeta potential is zero. Thus, the flow velocity at this point becomes zero, and the pressure gradient will be maximum. The direction of the flap motion is determined by the location of the stagnation point. As an example, here, it is shown that the obtuse conductive flap moves in the opposite direction of the flow field because in this case, the stagnation point is located on the back surface of the flap. Interaction of two vertical conductive flaps (located at different distances from each other) is also investigated in this paper. The results indicate that if both of the conductive flaps are fixed on the same microchannel wall, two vortices with opposite spin directions are generated between them. These vortices create a low-pressure zone through which the two flaps attract one another. However, when each flap is fixed on upper and lower microchannel walls, the two vortices with same spin directions are generated between the flaps. These two vortices merge and form a high-pressure zone through which two flaps repel each other.     

SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome**

Chemoproteomics has enabled the rapid and proteome-wide discovery of functional, redox-sensitive, and ligandable cysteine residues. Despite widespread adoption and considerable advances in both sample-preparation workflows and MS instrumentation, chemoproteomics experiments still typically only identify a small fraction of all cysteines encoded by the human genome. Here, we develop an optimized sample-preparation workflow that combines enhanced peptide labeling with single-pot, solid-phase-enhanced sample-preparation (SP3) to improve the recovery of biotinylated peptides, even from small sample sizes. By combining this improved workflow with on-line high-field asymmetric waveform ion mobility spectrometry (FAIMS) separation of labeled peptides, we achieve unprecedented coverage of >14000 unique cysteines in a single-shot 70 min experiment. Showcasing the wide utility of the SP3-FAIMS chemoproteomic method, we find that it is also compatible with competitive small-molecule screening by isotopic tandem orthogonal proteolysis–activity-based protein profiling (isoTOP-ABPP). In aggregate, our analysis of 18 samples from seven cell lines identified 34225 unique cysteines using only ∼28 h of instrument time. The comprehensive spectral library and improved coverage provided by the SP3-FAIMS chemoproteomics method will provide the technical foundation for future studies aimed at deciphering the functions and druggability of the human cysteineome.