Reduced VDAC1, Maintained Mitochondrial Dynamics and Enhanced Mitochondrial Biogenesis in a Transgenic Tau Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common forms of neurodegeneration, defined by reduced cognitive function, which is caused by the gradual death of neurons in the brain. Recent studies have shown an age-dependent rise in the levels of voltage-dependent anion channel 1 (VDAC1) in AD. In addition, we discovered an aberrant interaction between VDAC1 and P-TAU in the brains of AD patients, which led to abnormalities in the structural and functional integrity of the mitochondria. The purpose of our study is to understand the protective effects of reduced VDAC1 against impaired mitochondrial dynamics and defective mitochondrial biogenesis in transgenic TAU mice. Recently, we crossed heterozygote VDAC1 knockout (VDAC1^+/−) mice with transgenic TAU mice to obtain double-mutant VDAC1^+/−/TAU mice. Our goal was to evaluate whether a partial decrease in VDAC1 lessens the amount of mitochondrial toxicity in transgenic Tau (P301L) mice. We found that mitochondrial fission proteins were significantly reduced, and mitochondrial fusion and biogenesis proteins were increased in double-mutant mice compared to TAU mice. On the basis of these discoveries, the current work may have significance for the development of reduced-VDAC1-based treatments for individuals suffering from AD as well as other tauopathies.     

Response Surface Methodology Based Modelling of Friction–Wear Behaviour of Al6061/9%Gr/WC MMCs and Its Optimization Using Fuzzy GRA

In the present paper an attempt is made to establish a response surface methodology based non-linear mathematical model for the friction–wear behaviour of as cast and heat-treated Al6061/9%Gr/WC (with WC at 1, 2 and 3 wt%) metal matrix composites (MMCs). During experimentation, the process parameters, namely percentage of WC, load, sliding distance and sliding velocity have been considered as inputs and wear loss (WL) and coefficient of friction (COF) have been treated as the responses. Results reveal that, for as-cast Al6061/9%Gr/WC hybrid composites, the WL decreases with increase in percentage of WC and increases with the increase in load, sliding distance and sliding velocity. Moreover, COF decreases with increase in percentage of WC and sliding velocity and increases with increase in the load and sliding distance. It has also been observed that the WL and COF of heat treated composites are found to be less than the as cast MMCs. Further, fuzzy grey relational analysis (GRA) has been used to perform the multi objective optimization of the said wear process. Finally, the evidence of wear phenomenon for the said composites have been examined with the help of scanning electron microscopy.     

A low constraint center cracked Brazilian disk specimen for ductile FCC single crystal

International Journal of Fracture - In this work, the center cracked Brazilian disk (BD) geometry is proposed as a possible small-scale low crack tip constraint fracture specimen for ductile FCC...     

Multiple metastatic infections in a hemodialysis patient with untunneled internal jugular catheter

We present an end‐stage renal disease patient on dialysis with fever. The primary source was right internal jugular vein catheter which had metastatic infections in the body probably via an arteriovenous communication in a cavity in left lung. Patient had right psoas muscle abscess and a left kidney abscess. An ¹⁸F‐fluorodeoxyglucose‐positron emission spectroscopy scan was done to find out left kidney abscess. A search of literature did not reveal many patients of psoas abscess secondary to infection of hemodialysis access.     

Microwave drying of mango ginger (Curcuma amada Roxb): prediction of drying kinetics by mathematical modelling and artificial neural network

Curcuma amada (Mango ginger) was dried at four different power levels ranging 315–800 W to determine the effect of microwave power on moisture content, moisture ratio, drying rate, drying time and effective diffusivity. Among the fifteen thin layer drying models considered for evaluating the drying behaviour, the semi‐empirical Midilli et al., model described the drying kinetics very well with R² > 0.999. Drying rate and effective diffusivity increased as the microwave power output increased. Activation energy was estimated by a modified Arrhenius type equation and found to be 21.6 kW kg^?1. A feed‐forward artificial neural network using back‐propagation algorithm was also employed to predict the moisture content during MW drying and found adequate to predict the drying kinetics with R² of 0.985.     

Topical safety and vasoconstrictive assay-based bioequivalence of a new reformulated mometasone cream

Objectives: A new improved mometasone furoate (Elocon?) cream with an emulsification system that produces a stable emulsion has been developed. In order to register the product in various markets, it was essential to ensure the cream was topically well tolerated and that it was bioequivalent to the reference product.

Methods: Phase I clinical studies were performed to assess the local safety and tolerability upon multiple dosing of this new cream as well as to assess the single-dose bioequivalence relative to the marketed product. Bioequivalence was assessed using a vasoconstrictive assay (VCA) after a dose-duration pilot study was completed with the marketed Elocon cream.

Key findings: The new mometasone cream and its vehicle were nonirritating in healthy subjects during 21-day patch application (MCII <0.025). The positive control was moderately irritating in the same study. The pivotal VCA study enrolled 162 subjects with 105 detectors included in the analysis of bioequivalence. In the 105 detectors, the ratio (×100%) of AUEC values at ED₅₀ for test vs. standard (90% CI) was 112.91% (105.55, 120.87), within the bioequivalence criteria of (80, 125).

Conclusions: These studies supported the registration of reformulated mometasone cream in various markets.     

Speed–density functional relationship for heterogeneous traffic data: a statistical and theoretical investigation

This study is an attempt to establish a suitable speed–density functional relationship for heterogeneous traffic on urban arterials. The model must reproduce the traffic behaviour on traffic stream and satisfy all static and dynamic properties of speed–flow–density relationships. As a first attempt for Indian traffic condition, two behavioural parameters, namely the kinematic wave speed at jam (C_j) and a proposed saturation flow (λ), are estimated using empirical observations. The parameter C_j is estimated by developing a relationship between driver reaction time and vehicle position in the queue at the signalised intersection. Functional parameters are estimated using Levenberg–Marquardt algorithm implemented in the R statistical software. Numerical measures such as root mean squared error, average relative error and cumulative residual plots are used for assessing models fitness. We set out several static and dynamic properties of the flow–speed–density relationships to evaluate the models, and these properties equally hold good for both homogenous and heterogeneous traffic states. From the numerical analysis, it is found that very few models replicate empirical speed–density data traffic behaviour. However, none of the existing functional forms satisfy all the properties. To overcome the shortcomings, we proposed two new speed–density functional forms. The uniqueness of these models is that they satisfy both numerical accuracy and the properties of fundamental diagram. These new forms would certainly improve the modelling accuracy, especially in dynamic traffic studies when coupling with dynamic speed equations.

     

Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model

Background: The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson’s disease (PD).

Methods: Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20?mg/kg of body weight) at 2?h intervals. Immunohistochemistry was performed.

Results: Optimal MMEI was stable and non-ciliotoxic with 66.29?±?4.15?nm as average globule size and??20.9?±?3.98?mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p?<?0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups.

Conclusion: Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.     

Fabrication and characterisation of bulk micromachined ZnO energy transducer with interdigitated electrodes

The proposed research work deals with the design, fabrication and characterisation of a ZnO cantilever energy transducer on Si(c) without the use of SOI wafers, thereby, reducing the cost of fabrication. The energy transducer is operated in the longitudinal mode through the interdigitated electrodes. This is for the first time, we have attempted to fabricate a cantilever transducer with interdigitated electrodes on Si(c) in our lab. The design frequency has been chosen in the range of 700–1000 Hz for a typical tire pressure monitoring system application in mind. The experimentally obtained frequency is 876.25 Hz and d₃₃ was calculated as 3.9 pC/N from the measurements. The experimental results are further validated by simulation and the feasibility of its application as energy harvester is demonstrated. The fabrication process is being optimised to fabricate devices with higher piezoelectric coefficients.