Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder; it is the most common cause of dementia and has no treatment. It is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of Neurofibrillary tangles (NFTs). Yet, those two hallmarks do not explain the full pathology seen with AD, suggesting the involvement of other mechanisms. Neuroinflammation could offer another explanation for the progression of the disease. This review provides an overview of recent advances on the role of the immune cells’ microglia and astrocytes in neuroinflammation. In AD, microglia and astrocytes become reactive by several mechanisms leading to the release of proinflammatory cytokines that cause further neuronal damage. We then provide updates on neuroinflammation diagnostic markers and investigational therapeutics currently in clinical trials to target neuroinflammation.     

3D CFD validation of invert trap efficiency for sewer solid management using VOF model

Earlier investigators have numerically carried out performance analysis of the invert trap fitted in an open channel using the stochastic discrete phase model(DPM) by assuming the open channel flow to be closed conduit flow under pressure and assuming zero shear stress at the top wall.This is known as the fixed lid model.By assuming the top wall to be a shear free wall,they have been able to show that the velocity distribution looks similar to that of an open channel flow with zero velocity at the bottom and maximum velocity at the top,representing the free water surface,but no information has been provided for the pressure at the free water surface.Because of this assumption,the validation of the model in predicting the trap efficiency has performed significantly poorly.In addition,the free water surface subject to zero gauge pressure cannot be modeled using the fixed lid model because there is no provision of extra space in the form of air space for the fluctuating part of the water surface profile.It can.however,be modeled using the volume of fluid(VOF) model because the VOF model is the appropriate model for open channel or free surface flow.Therefore,in the present study,three-dimensional(3D) computational fluid dynamics(CFD) modeling with the VOF model,which considers open channel flow with a free water surface,along with the stochastic DPM.was used to model the trap efficiency of an invert trap fitted in an open rectangular channel.The governing mathematical flow equations of the VOF model were solved using the ANSYS Fluent 14.0 software,reproducing the experimental conditions exactly.The results show that the 3D CFD predictions using the VOF model closely fit the experimental data for glass bead particles.     

Estrogen content of dairy and swine wastes

Naturally occurring estrogens in animal wastes may cause negative environmental impacts, yet their abundance in animal waste treatment and storage structures is poorly documented. To better quantify estrogen concentrations in animal wastes, multiple waste samples were collected from treatment and storage structures at dairy and swine facilities and analyzed for concentrations of 17beta-estradiol (E2), estrone (E1), and 17alpha-estradiol by gas chromatography-mass spectroscopy and by enzyme linked immunosorbent assay (E2 only). Mass ratios of each estrogen to the macronutrients nitrogen, phosphorus, and potassium were also determined. Because manure application rates are typically macronutrient-based, estrogen to macronutrient ratios are proportional to areal mass application rates of estrogen to fields. Swine farrowing waste (from farrowing sows and piglets) had the highest ratios of E2 to macronutrients. Mean ratios in swine farrowing waste were roughly twice those in swine finishing waste (from growing male and nonpregnant female animals) and more than four times higher than those in dairy waste (from lactating cows in various stages of their reproductive cycles); these differences were statistically significant (alpha = 0.05). Estrone followed a similar trend. In contrast, ratios of 17alpha-estradiol to macronutrients were highest in dairy operations. These results can be used to better predict estrogen loading rates on fields receiving swine and dairy wastes.     

Genome-wide bacterial toxicity screening uncovers the mechanisms of toxicity of a cationic polystyrene nanomaterial

By exploiting a genome-wide collection of bacterial single-gene deletion mutants, we have studied the toxicological pathways of a 60-nm cationic (amino-functionalized) polystyrene nanomaterial (PS-NH(2)) in bacterial cells. The IC(50) of commercially available 60 nm PS-NH(2) was determined to be 158 μg/mL, the IC(5) is 108 μg/mL, and the IC(90) is 190 μg/mL for the parent E. coli strain of the gene deletion library. Over 4000 single nonessential gene deletion mutants of Escherichia coli were screened for the growth phenotype of each strain in the presence and absence of PS-NH(2). This revealed that genes clusters in the lipopolysaccharide biosynthetic pathway, outer membrane transport channels, ubiquinone biosynthetic pathways, flagellar movement, and DNA repair systems are all important to how this organism responds to cationic nanomaterials. These results, coupled with those from confirmatory assays described herein, suggest that the primary mechanisms of toxicity of the 60-nm PS-NH(2) nanomaterial in E. coli are destabilization of the outer membrane and production of reactive oxygen species. The methodology reported herein should prove generally useful for identifying pathways that are involved in how cells respond to a broad range of nanomaterials and for determining the mechanisms of cellular toxicity of different types of nanomaterials.     

Enhancing the design and performance of a gate-all-around (GAA) charge plasma nanowire field-effect transistor with the help of the negative-capacitance technique

A gate-all-around charge plasma nanowire field-effect transistor (GAA CP NW FET) device using the negative-capacitance technique is introduced, termed the GAA CP NW negative-capacitance (NC) FET. In the face of bottleneck issues in nanoscale devices such as rising power dissipation, new techniques must be introduced into FET structures to overcome their major limitations. Negative capacitance is an efficient effect that can be incorporated into a device to enhance its performance for low-power applications and help to reduce the operating voltage. The Landau–Khalatnikov equation can be applied in such cases to obtain the effective bias. To determine the effects of negative capacitance, lead zirconate titanate (PZT) ferroelectric material, a ceramic material with perovskite properties, is adopted as a gate insulator. This approach diminishes the supply voltage and reduces the power dissipation in the device. Excluding their polarization properties, ferroelectric materials are similar to dielectric materials, and PZT offers abundant polarization with improved reliability and a higher dielectric capacitance. Without proper tuning of the thickness of the PZT material, hysteresis behavior mat occur. Hence, the thickness of the PZT material (t_FE) is an essential parameter to optimize the device performance and achieve a reduced threshold voltage for the GAA CP NW NC-FET device proposed herein. Furthermore, varying the thickness of the PZT ferroelectric material can also enhance the performance. When using the highest values of t_FE, improved outcomes with an analogously lower operating voltage are observed. The effects of varying t_FE on the performance characteristics of the device including the drain current, transconductance, polarized charge, etc. are also interpreted herein.

     

The mitigation of signal integrity issues in coupled MWCNT bundles and a comparison with Cu interconnects

Journal of Computational Electronics - In the nanoscale regime, carbon nanotubes (CNTs) are being considered as a future alternative interconnect material for traditional copper (Cu) wires in...     

Mechanical property enhancement of non‐bonding electrospun mats via adhesive

In the present study, the effect of adhesive on the morphology of different electrospun polymeric mats was investigated. The modification of two polymers, poly(methyl methacrylate) and poly(vinyl chloride), was carried out by blending the polymers with different amounts of poly(butyl acrylate) (PBA) adhesive to investigate the effect of different amounts of adhesive with heat hardener in hybrid mats. The introduction of various concentrations of PBA into different polymer solutions led to the formation of point‐bonded electrospun fibrous mats. Scanning electron microscopy images indicated that point‐bonded polymer/adhesive fibers were uniformly distributed throughout the mats. Fourier transform infrared spectrometry, contact angle measurements and thermogravimetric analysis were used to study the different properties of the hybrid mats. The tensile strength of the blended fibrous electrospun mats was increased effectively. This enhancement of the mechanical properties of the mats due to the presence of adhesive increases the number of potential applications of the electrospun mats, especially for mechanically weak polymers. Copyright © 2012 Society of Chemical Industry     

Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside ( C-10 , chrysoeriol-7-O-β-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into β-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.     

A PHRASE GRAMMAR-BASED CONCEPTUAL INDEXING PARADIGM

ABSTRACT

Present day information retrieval systems largely ignore the issues of lexical and compositional semantics, and rely mainly on some statistical measures for choosing or evolving an indexing scheme. This has been the reason for the decreasing precision in their responses, given an exponentially increasing number of Web pages. The work reported in this paper addresses this issue from a linguistic point of view. We show that the detection of domain-specific phrases can capture the task-specific semantics of documents. We introduce the notion of n*-gram formalism to characterize the domain-specific phrases and their variants, taking a few sample domains. A method to construct a phrase grammar from a small set of documents is proposed. A method of conceptual indexing based on the phrase grammar has also been proposed. In order to demonstrate the effectiveness of the proposed method, we have designed a versatile system that can perform concept-based retrieval, in addition to several document-processing tasks, such as text classification, extraction-based summarization, context tracking, and semantic tagging. Collectively, the system can address the semantic content of documents. Considering the fact that an average user prefers highly relevant results in the top-ranked subset to an exhaustively retrieved set, it is shown that the proposed system performs better in that it retrieves documents that are more conceptually relevant than those retrieved by Google, and at 95% confidence level.     

Impact of oxygenated cottonseed biodiesel on combustion,performance and emission parameters in a direct injection CI engine

In the present study, biodiesel production from the crude cotton-seed oil (CSO) and its feasibility to be used as fuel in compression ignition engine was analysed. Single-stage transesterification at molar ratio of 8:1 on crude CSO yielded 94% of cottonseed biodiesel (CBD). Gas chromatogram/mass spectrometry analysis revealed the presence of 19.5% unsaturated and 80.5% saturated esters in cotton seed biodiesel. Taguchi approach identified the stable fuel blend with oxygenate concentration. Increased oxygen concentration up to 20% were also analysed to understand the variation. Higher peak in-cylinder pressure was observed in D80CBD20 fuel blend. Diesel–biodiesel blend with oxygenate significantly affected the ignition delay and also resulted in varied exhaust gas temperature. D80CBD20nB10 showed an increase in brake thermal efficiency, whereas D80CBD20 exhibited higher brake specific energy consumption at full load. Carbon monoxide, hydrocarbon and smoke emission was found to be high in diesel with higher oxides of nitrogen in D80CBD20nB10. This experimental investigation finally revealed that, D80CBD20nB10 improved the combustion and performance characteristics with minimal emissions.

Abbreviations ASTM: American Society for Testing and Materials; BP: brake power; BSEC: brake specific energy consumption; BTE: brake thermal efficiency; CBD: cottonseed biodiesel; CI: compression ignition; CO: carbon monoxide; CO₂: carbon dioxide; CSO: cottonseed oil; DEE: diethyl ether; DOE: design of experiments; EGT: exhaust gas temperature; FTIR: Fourier transform infrared spectrometry; GC/MS: gas chromatogram/mass spectrometry; HC: hydrocarbon; HRR: heat release rate; HSDI: high speed direct injection; IDI: indirect injection; KOH: potassium hydroxide; MFB: mass fraction burned; NaOH: sodium hydroxide; NMR: nuclear magnetic resonance; N₂O: nitrous oxide; NO: nitric oxide; NO₂: nitrogen dioxide; NO _x : oxides of nitrogen; ROHR: rate of heat release; ROPR: rate of pressure rise; SOC: start of combustion; aTDC: after top dead centre; bTDC: before top dead centre