Training of Cc4 Neural Network Using Unary and Spread Unary Inputs

This thesis presents results on training the corner classification (CC4) feed forward neural networks with the recently proposed spread unary inputs. We show the performance of this network is quite like that of the original CC4 network. The spread unary CC4 network is tested on pattern classification data. It is also used in time series prediction which is illustrated using the Mackey-Glass time series, sunspot predictions and the prediction of d-sequences.Electrical Engineerin

Контролируемые прочностные показатели для различных видов мебели

Методические указания по курсам «Расчет конструкций изделий из древесины и испытания мебели», «Технология изделий из древесины» для выполнения практических и лабораторных работ обучающимися по направлениям 35.03.02, 35.04.02 «Технология лесозаготовительных и деревоперерабатывающих производств», профиль «Технология деревообработки

Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria

BACKGROUND: Emergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors. METHODS: A collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection. RESULTS: A compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 microM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-a-go-go-Related Gene (hERG) liability (> 100 microM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 microM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 microM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously. CONCLUSION: FNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed

"Fake it till You Make it"! Contaminating Rubber Hands ("Multisensory Stimulation Therapy") to Treat Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a deeply enigmatic psychiatric condition associated with immense suffering worldwide. Efficacious therapies for OCD, like exposure and response prevention (ERP), are sometimes poorly tolerated by patients. As many as 25% of patients refuse to initiate ERP mainly because they are too anxious to follow exposure procedures. Accordingly, we proposed a simple and tolerable (immersive yet indirect) low-cost technique for treating OCD that we call "multisensory stimulation therapy." This method involves contaminating a rubber hand during the so-called "rubber hand illusion" (RHI) in which tactile sensations may be perceived as arising from a fake hand. Notably, Jalal et al. (2015) showed that such fake hand contamination during the RHI provokes powerful disgust reactions in healthy volunteers. In the current study, we explored the therapeutic potential of this novel approach. OCD patients (n = 29) watched as their hidden real hand was being stroked together with a visible fake hand; either synchronously (inducing the RHI; i.e., the experimental condition; n = 16) or asynchronously (i.e., the control condition; n = 13). After 5 min of tactile stimulation, the rubber hand was contaminated with fake feces, simulating conventional exposure therapy. Intriguingly, results suggested sensory assimilation of contamination sensations into the body image via the RHI: patients undergoing synchronous stimulation did not report greater contamination sensations when the fake hand was initially contaminated relative to asynchronous stroking. But contrary to expectations, they did so after the rubber hand had been contaminated for 5 min, as assessed via disgust facial expressions (a secondary outcome) and in vivo exposure (upon discontinuing the illusion). Further, to our surprise, synchronous and asynchronous stroking induced an equally vivid and fast-emerging illusion, which helps explain why both conditions initially (5 min after initiating tactile stimulation) provoked contamination reactions of equal magnitude. This study is the first to suggest heightened malleability of body image in OCD. Importantly, it may pave the way for a tolerable technique for the treatment of OCD-highly suitable for poorly resourced and emergency settings, including low-income and developing countries with minimal access to high-tech solutions like virtual reality

Forming low-cost, high quality carbon tows for automotive application.

Carbon fiber reinforced composites are widely used in many industries due to their high performance. Its application in the aerospace industry has increased significantly, however, in mass produced automobile sector it is still limited. The current production of carbon fiber tow is slow and capital intensive. Thus, carbon manufactures produce higher tow counts to increase production rate to reduce its cost. In order to offset the higher cost of carbon fiber composite, an innovative and unique approach has been developed. The higher tow count carbon spools are split into smaller tow counts. Due to the delicate nature of carbon fiber, it is important to control the filamentation during that process. Different splitting process line strategies have been developed in this research work for understanding the process limitations and challenges involved. The process was made feasible for production by developing a fully automated process line with a laser feedback system. The system splits a 12K spool into two 6K tows. The quality of the 6K split tows has been determined statistically by recording real time data from the laser during the splitting process. It was demonstrated that the proposed process effectively controls filamentation and produces consistent tow quality.Company research funding by Bentley Motors Limite

The Weighted Independent Domination Problem: ILP Model and Algorithmic Approaches

This work deals with the so-called weighted independent domination problem, which is an $NP$-hard combinatorial optimization problem in graphs. In contrast to previous work, this paper considers the problem from a non-theoretical perspective. The first contribution consists in the development of three integer linear programming models. Second, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy metaheuristic which is applied in two different ways: (1) the metaheuristic is applied directly to each problem instance, and (2) the metaheuristic is applied at each iteration of a higher-level framework---known as construct, merge, solve \& adapt---to sub-instances of the tackled problem instances. The results of the considered algorithmic approaches show that integer linear programming approaches can only compete with the developed metaheuristics in the context of graphs with up to 100 nodes. When larger graphs are concerned, the application of the populated-based iterated greedy algorithm within the higher-level framework works generally best. The experimental evaluation considers graphs of different types, sizes, densities, and ways of generating the node and edge weights

The weighted independent domination problem: ILP model and algorithmic approaches

This work deals with the so-called weighted independent domination problem, which is an N P -hard combinatorial optimization problem in graphs. In contrast to previous theoretical work from the liter- ature, this paper considers the problem from an algorithmic perspective. The first contribution consists in the development of an integer linear programming model and a heuristic that makes use of this model. Sec- ond, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy algorithm that takes profit from the better one of the two developed greedy heuristics. The results of the compared algorithmic approaches show that small problem instances based on random graphs are best solved by an efficient integer linear programming solver such as CPLEX. Larger problem instances are best tackled by the population-based iterated greedy algorithm. The experimental evaluation considers random graphs of different sizes, densities, and ways of generating the node and edge weights