VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Deterministic Random Number Generator Algorithm for Cryptosystem Keys

One of the crucial parameters of digital cryptographic systems is the selection of the keys used and their distribution. The randomness of the keys has a strong impact on the system’s security strength being difficult to be predicted, guessed, reproduced, or discovered by a cryptanalyst. Therefore, adequate key randomness generation is still sought for the benefit of stronger cryptosystems. This paper suggests an algorithm designed to generate and test pseudo random number sequences intended for cryptographic applications. This algorithm is based on mathematically manipulating a publically agreed upon information between sender and receiver over a public channel. This information is used as a seed for performing some mathematical functions in order to generate a sequence of pseudorandom numbers that will be used for encryption/decryption purposes. This manipulation involves permutations and substitutions that fulfill Shannon’s principle of “confusion and diffusion”. ASCII code characters were utilized in the generation process instead of using bit strings initially, which adds more flexibility in testing different seed values. Finally, the obtained results would indicate sound difficulty of guessing keys by attackers.

CMT4G – Rare Form of Charcot-Marie-Tooth Disease in Slovak Roma Patient

The Roma (Gypsies) is a transnational minority with a high degree of consanguineous marriages. Similar to other genetically isolated founder populations, the Roma harbor a number of unique or rare genetic disorders. This paper discusses about a rare form of Charcot-Marie-Tooth disease – type 4G (CMT4G), also called Hereditary Motor and Sensory Neuropathy type Russe, an autosomal recessive disease caused by mutation private to Roma characterized by abnormally increased density of non-myelinated axons. CMT4G was originally found in Bulgarian Roma and in 2009 two putative causative mutations in the HK1 gene were identified. Since then, several cases were reported in Roma families mainly from Bulgaria and Spain. Here we present a Slovak Roma family in which CMT4G was diagnosed on the basis of clinical examination and genetic testing. This case is a further proof of the role of the HK1 gene in pathogenesis of the disease. It confirms that mutation in the HK1 gene is a common cause of autosomal recessive CMT disease in Roma and should be considered as a common part of a diagnostic procedure.

Optimization of Flexible Job Shop Scheduling Problem with Sequence Dependent Setup Times Using Genetic Algorithm Approach

This paper presents optimization of makespan for ‘n’ jobs and ‘m’ machines flexible job shop scheduling problem with sequence dependent setup time using genetic algorithm (GA) approach. A restart scheme has also been applied to prevent the premature convergence. Two case studies are taken into consideration. Results are obtained by considering crossover probability (pc = 0.85) and mutation probability (pm = 0.15). Five simulation runs for each case study are taken and minimum value among them is taken as optimal makespan. Results indicate that optimal makespan can be achieved with more than one sequence of jobs in a production order.

High-Voltage Resonant Converter with Extreme Load Variation: Design Criteria and Applications

The power converter that feeds high-frequency, highvoltage transformers must be carefully designed due to parasitic components, mainly the secondary winding capacitance and the leakage inductance, that introduces resonances in relatively lowfrequency range, next to the switching frequency. This paper considers applications in which the load (resistive) has an unpredictable behavior, changing from open to short-circuit condition faster than the output voltage control loop could react. In this context, to avoid overvoltage and over current situations, that could damage the converter, the transformer or the load, it is necessary to find an operation point that assure the desired output voltage in spite of the load condition. This can done adjusting the frequency response of the transformer adding an external inductance, together with selecting the switching frequency to get stable output voltage independently of the load.

Exponentiated Transmuted Weibull Distribution A Generalization of the Weibull Distribution

This paper introduces a new generalization of the two parameter Weibull distribution. To this end, the quadratic rank transmutation map has been used. This new distribution is named exponentiated transmuted Weibull (ETW) distribution. The ETW distribution has the advantage of being capable of modeling various shapes of aging and failure criteria. Furthermore, eleven lifetime distributions such as the Weibull, exponentiated Weibull, Rayleigh and exponential distributions, among others follow as special cases. The properties of the new model are discussed and the maximum likelihood estimation is used to estimate the parameters. Explicit expressions are derived for the quantiles. The moments of the distribution are derived, and the order statistics are examined.

An Intelligent Approach for Management of Hybrid DG System

Distributed generation units (DGs) are grid-connected or stand-alone electric generation units located within the electric distribution system at or near the end user. It is generally accepted that centralized electric power plants will remain the major source of the electric power supply for the near future. DGs, however, can complement central power by providing incremental capacity to the utility grid or to an end user. This paper presents an efficient power dispatching model for hybrid wind-Solar power generation system, to satisfy some essential requirements, such as dispersed electric power demand, electric power quality and reducing generation cost and so on. In this paper, presented some elements of the main parts in the hybrid system; and then made fundamental dispatching strategies according to different situations; then pointed out four improving measures to improve genetic algorithm, such as: modify the producing way of selection probability, improve the way of crossover, protect excellent chromosomes, and change mutation range and so on. Finally, propose a technique for solving the unit's commitment for dispatching problem based on an improved genetic algorithm.

Applying Sequential Pattern Mining to Generate Block for Scheduling Problems

The main idea in this paper is using sequential pattern mining to find the information which is helpful for finding high performance solutions. By combining this information, it is defined as blocks. Using the blocks to generate artificial chromosomes (ACs) could improve the structure of solutions. Estimation of Distribution Algorithms (EDAs) is adapted to solve the combinatorial problems. Nevertheless many of these approaches are advantageous for this application, but only some of them are used to enhance the efficiency of application. Generating ACs uses patterns and EDAs could increase the diversity. According to the experimental result, the algorithm which we proposed has a better performance to solve the permutation flow-shop problems.

An Improved Ant Colony Algorithm for Genome Rearrangements

Genome rearrangement is an important area in computational biology and bioinformatics. The basic problem in genome rearrangements is to compute the edit distance, i.e., the minimum number of operations needed to transform one genome into another. Unfortunately, unsigned genome rearrangement problem is NP-hard. In this study an improved ant colony optimization algorithm to approximate the edit distance is proposed. The main idea is to convert the unsigned permutation to signed permutation and evaluate the ants by using Kaplan algorithm. Two new operations are added to the standard ant colony algorithm: Replacing the worst ants by re-sampling the ants from a new probability distribution and applying the crossover operations on the best ants. The proposed algorithm is tested and compared with the improved breakpoint reversal sort algorithm by using three datasets. The results indicate that the proposed algorithm achieves better accuracy ratio than the previous methods.

An Efficient Separation for Convolutive Mixtures

This paper describes a new efficient blind source separation method; in this method we uses a non-uniform filter bank and a new structure with different sub-bands. This method provides a reduced permutation and increased convergence speed comparing to the full-band algorithm. Recently, some structures have been suggested to deal with two problems: reducing permutation and increasing the speed of convergence of the adaptive algorithm for correlated input signals. The permutation problem is avoided with the use of adaptive filters of orders less than the full-band adaptive filter, which operate at a sampling rate lower than the sampling rate of the input signal. The decomposed signals by analysis bank filter are less correlated in each sub-band than the input signal at full-band, and can promote better rates of convergence.

Supremacy of Differential Evolution Algorithm in Designing Multiplier-Less Low-Pass FIR Filter

In this communication, we have made an attempt to design multiplier-less low-pass finite impulse response (FIR) filter with the aid of various mutation strategies of Differential Evolution (DE) algorithm. Impulse response coefficient of the designed FIR filter has been represented as sums or differences of powers of two. Performance of the proposed filter has been evaluated in terms of its frequency response and associated hardware cost. Supremacy of our approach has been substantiated by comparing our result with many of the existing multiplier-less filter design algorithms of recent interest. It has also been demonstrated that DE-optimized filter outperforms Genetic Algorithm (GA) based design by a large margin.  Hardware efficiency of our algorithm has further been validated by implementing those filters on a Field Programmable Gate Array (FPGA) chip.

System Reduction by Eigen Permutation Algorithm and Improved Pade Approximations

A mixed method by combining a Eigen algorithm and improved pade approximations is proposed for reducing the order of the large-scale dynamic systems. The most dominant Eigen value of both original and reduced order systems remain same in this method. The proposed method guarantees stability of the reduced model if the original high-order system is stable and is comparable in quality with the other well known existing order reduction methods. The superiority of the proposed method is shown through examples taken from the literature.

Study of Functional Relevant Conformational Mobility of β-2 Adrenoreceptor by Means of Molecular Dynamics Simulation

The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behavior.

A Review of Genetic Algorithm Optimization: Operations and Applications to Water Pipeline Systems

Genetic Algorithm (GA) is a powerful technique for solving optimization problems. It follows the idea of survival of the fittest - Better and better solutions evolve from previous generations until a near optimal solution is obtained. GA uses the main three operations, the selection, crossover and mutation to produce new generations from the old ones. GA has been widely used to solve optimization problems in many applications such as traveling salesman problem, airport traffic control, information retrieval (IR), reactive power optimization, job shop scheduling, and hydraulics systems such as water pipeline systems. In water pipeline systems we need to achieve some goals optimally such as minimum cost of construction, minimum length of pipes and diameters, and the place of protection devices. GA shows high performance over the other optimization techniques, moreover, it is easy to implement and use. Also, it searches a limited number of solutions.

Optimization of Electrospinning Parameter by Employing Genetic Algorithm in order to Produce Desired Nanofiber Diameter

A numerical simulation of optimization all of electrospinning processing parameters to obtain smallest nanofiber diameter have been performed by employing genetic algorithm (GA). Fitness function in genetic algorithm methods, which was different for each parameter, was determined by simulation approach based on the Reneker’s model. Moreover, others genetic algorithm parameter, namely length of population, crossover and mutation were applied to get the optimum electrospinning processing parameters. In addition, minimum fiber diameter, 32 nm, was achieved from a simulation by applied the optimum parameters of electrospinning. This finding may be useful for process control and prediction of electrospun fiber production. In this paper, it is also compared between predicted parameters with some experimental results.

Identification of Non-Lexicon Non-Slang Unigrams in Body-enhancement Medicinal UBE

Email has become a fast and cheap means of online communication. The main threat to email is Unsolicited Bulk Email (UBE), commonly called spam email. The current work aims at identification of unigrams in more than 2700 UBE that advertise body-enhancement drugs. The identification is based on the requirement that the unigram is neither present in dictionary, nor is a slang term. The motives of the paper are many fold. This is an attempt to analyze spamming behaviour and employment of wordmutation technique. On the side-lines of the paper, we have attempted to better understand the spam, the slang and their interplay. The problem has been addressed by employing Tokenization technique and Unigram BOW model. We found that the non-lexicon words constitute nearly 66% of total number of lexis of corpus whereas non-slang words constitute nearly 2.4% of non-lexicon words. Further, non-lexicon non-slang unigrams composed of 2 lexicon words, form more than 71% of the total number of such unigrams. To the best of our knowledge, this is the first attempt to analyze usage of non-lexicon non-slang unigrams in any kind of UBE.

An Improved Genetic Algorithm to Solve the Traveling Salesman Problem

The Genetic Algorithm (GA) is one of the most important methods used to solve many combinatorial optimization problems. Therefore, many researchers have tried to improve the GA by using different methods and operations in order to find the optimal solution within reasonable time. This paper proposes an improved GA (IGA), where the new crossover operation, population reformulates operation, multi mutation operation, partial local optimal mutation operation, and rearrangement operation are used to solve the Traveling Salesman Problem. The proposed IGA was then compared with three GAs, which use different crossover operations and mutations. The results of this comparison show that the IGA can achieve better results for the solutions in a faster time.

Bioinformatic Analysis of Retroelement-Associated Sequences in Human and Mouse Promoters

Mammalian genomes contain large number of retroelements (SINEs, LINEs and LTRs) which could affect expression of protein coding genes through associated transcription factor binding sites (TFBS). Activity of the retroelement-associated TFBS in many genes is confirmed experimentally but their global functional impact remains unclear. Human SINEs (Alu repeats) and mouse SINEs (B1 and B2 repeats) are known to be clustered in GCrich gene rich genome segments consistent with the view that they can contribute to regulation of gene expression. We have shown earlier that Alu are involved in formation of cis-regulatory modules (clusters of TFBS) in human promoters, and other authors reported that Alu located near promoter CpG islands have an increased frequency of CpG dinucleotides suggesting that these Alu are undermethylated. Human Alu and mouse B1/B2 elements have an internal bipartite promoter for RNA polymerase III containing conserved sequence motif called B-box which can bind basal transcription complex TFIIIC. It has been recently shown that TFIIIC binding to B-box leads to formation of a boundary which limits spread of repressive chromatin modifications in S. pombe. SINEassociated B-boxes may have similar function but conservation of TFIIIC binding sites in SINEs located near mammalian promoters has not been studied earlier. Here we analysed abundance and distribution of retroelements (SINEs, LINEs and LTRs) in annotated sequences of the Database of mammalian transcription start sites (DBTSS). Fractions of SINEs in human and mouse promoters are slightly lower than in all genome but >40% of human and mouse promoters contain Alu or B1/B2 elements within -1000 to +200 bp interval relative to transcription start site (TSS). Most of these SINEs is associated with distal segments of promoters (-1000 to -200 bp relative to TSS) indicating that their insertion at distances >200 bp upstream of TSS is tolerated during evolution. Distribution of SINEs in promoters correlates negatively with the distribution of CpG sequences. Using analysis of abundance of 12-mer motifs from the B1 and Alu consensus sequences in genome and DBTSS it has been confirmed that some subsegments of Alu and B1 elements are poorly conserved which depends in part on the presence of CpG dinucleotides. One of these CpG-containing subsegments in B1 elements overlaps with SINE-associated B-box and it shows better conservation in DBTSS compared to genomic sequences. It has been also studied conservation in DBTSS and genome of the B-box containing segments of old (AluJ, AluS) and young (AluY) Alu repeats and found that CpG sequence of the B-box of old Alu is better conserved in DBTSS than in genome. This indicates that Bbox- associated CpGs in promoters are better protected from methylation and mutation than B-box-associated CpGs in genomic SINEs. These results are consistent with the view that potential TFIIIC binding motifs in SINEs associated with human and mouse promoters may be functionally important. These motifs may protect promoters from repressive histone modifications which spread from adjacent sequences. This can potentially explain well known clustering of SINEs in GC-rich gene rich genome compartments and existence of unmethylated CpG islands.

Multi-matrix Real-coded Genetic Algorithm for Minimising Total Costs in Logistics Chain Network

The importance of supply chain and logistics management has been widely recognised. Effective management of the supply chain can reduce costs and lead times and improve responsiveness to changing customer demands. This paper proposes a multi-matrix real-coded Generic Algorithm (MRGA) based optimisation tool that minimises total costs associated within supply chain logistics. According to finite capacity constraints of all parties within the chain, Genetic Algorithm (GA) often produces infeasible chromosomes during initialisation and evolution processes. In the proposed algorithm, chromosome initialisation procedure, crossover and mutation operations that always guarantee feasible solutions were embedded. The proposed algorithm was tested using three sizes of benchmarking dataset of logistic chain network, which are typical of those faced by most global manufacturing companies. A half fractional factorial design was carried out to investigate the influence of alternative crossover and mutation operators by varying GA parameters. The analysis of experimental results suggested that the quality of solutions obtained is sensitive to the ways in which the genetic parameters and operators are set.

Feeder Reconfiguration for Loss Reduction in Unbalanced Distribution System Using Genetic Algorithm

This paper presents an efficient approach to feeder reconfiguration for power loss reduction and voltage profile imprvement in unbalanced radial distribution systems (URDS). In this paper Genetic Algorithm (GA) is used to obtain solution for reconfiguration of radial distribution systems to minimize the losses. A forward and backward algorithm is used to calculate load flows in unbalanced distribution systems. By simulating the survival of the fittest among the strings, the optimum string is searched by randomized information exchange between strings by performing crossover and mutation. Results have shown that proposed algorithm has advantages over previous algorithms The proposed method is effectively tested on 19 node and 25 node unbalanced radial distribution systems.