Pharmacotherapeutics and molecular docking studies of alpha-synuclein modulators as promising therapeutics for Parkinson’s disease

Parkinson’s disease (PD) is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain. It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain. To date, only a few Food and Drug Administration (FDA) approved drugs are available on the market for the treatment of PD. Nonetheless, these drugs show parasympathomimetic related adverse events and remarkably higher toxicity; hence, it is important to find more efficacious molecules to treat PD. In our study, We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump—the pathological hallmark of PD—and provide new avenues for its treatment. Most of these molecules exhibited good pharmacokinetic behaviors, making them decisively favorable drug candidates to cure PD. Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets. Among the examined compounds, curcumin and piperine emerged as promising phytochemicals with the highest binding affinity, key residual stable bindings and showed a good inhibitory features. Thus, the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD. Experimental validations are needed for insights into their mechanism of action and potential clinical application.     

Locality Aware Optimal Task Scheduling Algorithm for TriBA——A Novel Scalable Architecture

An optimal algorithmic approach to task scheduling for, triplet based architecture（TriBA）, is proposed in this paper. TriBA is considered to be a high performance, distributed parallel computing architecture. TriBA consists of a 2D grid of small, programmable processing units, each physically connected to its three neighbors. In parallel or distributed environment an efficient assignment of tasks to the processing elements is imperative to achieve fast job turnaround time. Moreover, the sojourn time experienced by each individual job should be minimized. The arriving jobs are comprised of parallel applications, each consisting of multiple-independent tasks that must be instantaneously assigned to processor queues, as they arrive. The processors independently and concurrently service these tasks. The key scheduling issues is, when some queue backlogs are small, an incoming job should first spread its tasks to those lightly loaded queues in order to take advantage of the parallel processing gain. Our algorithmic approach achieves optimality in task scheduling by assigning consecutive tasks to a triplet of processors exploiting locality in tasks. The experimental results show that tasks allocation to triplets of processing elements is efficient and optimal. Comparison to well accepted interconnection strategy, 2D mesh, is shown to prove the effectiveness of our algorithmic approach for TriBA. Finally we conclude that TriBA can be an efficient interconnection strategy for computations intensive applications, if tasks assignment is carried out optimally using algorithmic approach.     

Simultaneous External and Internal Stabilization for Continuous and Discrete-Time Critically Unstable Linear Systems with Saturating Actuators

The issues arising in hybrid or simultaneous external as well as internal stabilization of linear systems with saturating actuators are considered. Four different stabilization problems are studied. Roughly, these problems are (1) simultaneous semi-global external as well as semi-global internal stabilization, (2) simultaneous semi-global external as well as global internal stabilization, (3) simultaneous global external as well as semi-global internal stabilization, and (4) simultaneous global external as well as global internal stabilization. As evident from the literature, the requirement of internal stabilization alone either in the global or semi-global sense demands that the linear part of the given system be (a) stabilizable, and (b) has all its poles in the closed left half complex plane for continuous-time systems while it has all its poles inside and/or on the unit circle for discrete-time systems. This implies that the posed simultaneous stabilization problems are solvable at best only under the conditions (a) and (b). Under such conditions, we construct here explicit state as well as measurement feedback controllers for all the four problems in the case of continuous-time systems, and for the problems (1), (2) and (4) in the case of discrete-time systems. The design methodologies used to construct appropriate feedback laws are based on by now familiar low-gain and low-and-high gain design concepts or certain scheduled versions of them.     

A survey on trust based detection and isolation of malicious nodes in ad-hoc and sensor networks

Mobile ad-hoc networks (MANETs) and wireless sensor networks (WSNs) have gained remarkable appreciation and technological development over the last few years. Despite ease of deployment, tremendous applications and significant advantages, security has always been a challenging issue due to the nature of environments in which nodes operate. Nodes’ physical capture, malicious or selfish behavior cannot be detected by traditional security schemes. Trust and reputation based approaches have gained global recognition in providing additional means of security for decision making in sensor and ad-hoc networks. This paper provides an extensive literature review of trust and reputation based models both in sensor and ad-hoc networks. Based on the mechanism of trust establishment, we categorize the stateof-the-art into two groups namely node-centric trust models and system-centric trust models. Based on trust evidence, initialization, computation, propagation and weight assignments, we evaluate the efficacy of the existing schemes. Finally, we conclude our discussion with identification of some unresolved issues in pursuit of trust and reputation management.     

Selecting and prioritizing key factors for CAD/CAM software in small- and medium-sized enterprises using AHP

In today’s fast-paced world, computer-aided design/computer-aided manufacturing (CAD/CAM) systems have become a necessary element in manufacturing industries. Prior to investment in a CAD/CAM system, it is essential for investor to know how to maximize their benefits from buying a new or by changing an existing CAD/CAM system. The purpose of this study is to provide a methodology to assist small- and medium-sized manufacturing companies of Pakistan in selecting a CAD/CAM system. It will also facilitate the software providers in recognizing the current state of affairs as well as preceding problems regarding the application of CAD/CAM in manufacturing firms when assisting them in choosing the direction for future development simultaneously. To accomplish this purpose, data have been collected about current CAD/CAM systems. Important criteria for system selection and parameters for evaluation have also been identified and prioritized. Analytic hierarchy process (AHP) is used as a decision-making technique for identifying and prioritizing important factors for CAD/CAM software selection. Expert Choice (AHP-based software) has been used to validate the results.     

Brief Note: Isolation,culture, characterization and optimization of human corneal stem cells

The effects of human versus mouse EGF on cell growth and culture duration were studied to optimize a human limbal stem cells culture method for therapeutical autologous transplantation. Limbal cells were obtained by trypsin digestion and transferred to a culture medium. The time needed to reach full confluence in culture was determined. Specific antibodies to corneal stem cell marker (P63) versus corneal epithelial differentiation marker (K3) were used for histochemical determinations. A high proportion of P63 positive cells (85± 4.6%), and a correspondingly low proportion K3 positive cells (15 ± 3.8%) indicated that most cultured cells remained undifferentiated and were considered as stem cells (mean ± SE, n=10). Cultures reached full confluency after 17.3 ± 1.2 days when the medium was supplemented with human EGF, while 21.7 ± 1.5 days were needed when the medium was supplemented with mouse EGF. The results showed that limbal stem cells proliferate more easily and reach to full confluency in a shorter time if the medium is supplemented with hEGF rather than with mEGF.     

Comparative Study of Plasma Parameters in Magnetic Pole Enhanced Inductively Coupled Argon Plasmas

Langmuir probe measurements of radio frequency (RF) magnetic pole enhanced inductively coupled (MaPE-ICP) argon plasma were accomplished to obtain the electron number densities and electron temperatures. The measurements were carried out with a fixed RF frequency of 13.56 MHz in a pressure range of 7.5 mTorr to 75 mTorr at an applied RF power of 10 W and 100 W. These results are compared with a global (volume average) model. The results show good agreement between theoretical and experimental measurements. The electron number density shows an increasing trend with both RF power and pressure while the electron temperature shows decreasing trend as the pressure increases. The difference in the plasma potential and floating potential as a function of electron temperature measured from the electrical probe and that obtained theoretically shows a linear relation with a small difference in the coefficient of proportionality. The intensity of the emission line at 750.4 nm due to 2p 1 → 1s 2 (Paschen’s notation) transition closely follows the variation of n e with RF power and filling gas pressure. Measured electron energy probability function (EEPF) shows that electron occupation changes mostly in the high-energy tail, which highlights close similarity of 750.4 nm argon line to n e .     

Optimization and comparison of two different 3D culture methods to prepare cell aggregates as a bioink for organ printing

The ultimate goal of tissue engineering is to design and fabricate functional human tissues that are similar to natural cells and are capable of regeneration. Preparation of cell aggregates is one of the important steps in 3D tissue engineering technology, particularly in organ printing. Two simple methods, hanging drop (HD) and conical tube (CT) were utilized to prepare cell aggregates. The size and viability of the aggregates obtained at different initial cell densities and pre-culture duration were compared. The proliferative ability of the cell aggregates and their ability to spread in culture plates were also investigated. In both methods, the optimum average size of the aggregates was less than 500 μm. CT aggregates were smaller than HD aggregates. 5,000 cells per drop HD aggregates showed a marked ability to attach and spread on the culture surface. The proliferative ability reduced when the initial cell density was increased. Comparing these methods, we found that the HD method having better size controlling ability as well as enhanced ability to maintain higher rates of viability, spreading, and proliferation. In conclusion, smaller HD aggregates might be a suitable choice as building blocks for making bioink particles in bioprinting technique.     

Trace-Rare-Gas Optical Emission Spectroscopy of Nitrogen Plasma Generated at a Frequency of 13.56 MHz

Optical emission spectroscopic measurement of trace rare gas is carried out to determine the density of nitrogen (N) atom, in a nitrogen plasma, as a function of filling pressure and RF power applied. 2% of argon, used as an actinometer, is mixed with nitrogen. In order to normalize the changes in the excitation cross section and electron energy distribution function at different operational conditions, the Ar-I emission line at 419.83 nm is used, which is of nearly the same excitation efficiency coefficients as that of the nitrogen emission line at 493.51 nm. It is observed that the emission intensity of the selected argon and atomic nitrogen lines increases with both pressure and RF power, as does the nitrogen atomic density.     

Decoration of vertically aligned TiO2 nanotube arrays with WO3 particles for hydrogen fuel production

WO₃ decorated photoelectrodes of titanium nanotube arrays (W-oxide TNTAs) were synthesized via a two-step process, namely, electrochemical oxidation of titanium foil and electrodeposition of W-oxide for various interval times of 1, 2, 3, 5, and 20 min to improve the photoelectrochemical performance and the amount of hydrogen generated. The synthesized photoelectrodes were characterized by various characterization techniques. The presence of tungsten in the modified TNTAs was confirmed using energy dispersive X-ray spectroscopy (EDX). Field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscope (HRTEM) proved the deposition of W-oxide as small particles staked up on the surface of the tubes at lower deposition time whereas longer times produced large and aggregate particles to mostly cover the surface of TiO₂ nanotubes. Additionally, the incorporation of WO₃ resulted in a shift of the absorption edge toward visible light as confirmed by UV-Vis diffuse reflectance spectroscopy and a decrease in the estimated band gap energy values hence, modified TNTAs facilitated a more efficient utilization of solar light for water splitting. From the photoelectrochemical measurement data, the optimal photoelectrode produced after 2 min of deposition time improved the photo conversion efficiency and the hydrogen generation by 30% compared to that of the pure TNTA.