Recent Developments in the Chemistry and Biology of G-Quadruplexes with Reference to the DNA Groove Binders

DNA is the chemotherapeutic target for treating diseases of genetic origin. Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA etc.), DNA is capable of forming several multi-stranded structures (triplex, tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3'-ends of chromosomes, called telomeres, are synthesized by telomerase, a ribonucleoprotein, and over-expression of telomerase is associated with cancer. The activity of telomerase is suppressed if the G-rich region is folded into the four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic ligands. Thus design and synthesis of new G4-DNA ligands is an attractive strategy to combat cancer. G4-DNA forming sequences are also prevalent in other genomic regions of biological significance including promoter regions of several oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA structure within the G-rich promoter sequences. To date, several G4-DNA stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA through the grooves (major and minor groove) in a sequence-specific manner. Some of the groove binders are known to stabilize the G4-DNA. However, this is a relatively under explored field of research. In this review, we focus on the recent advances in the understanding of the G4-DNA structures, particularly made from the human telomeric DNA stretches. We summarize the results of various investigations of the interaction of various organic ligands with the G4-DNA while highlighting the importance of groove binder-G4-DNA interactions.

Statistical Methods for Accelerated Life Testing with Particular Reference to Resin Impregnated Paper Bushings

Electrical failure of insulation is known to be an extremal random process wherein nominally identical pro-rated specimens of equipment insulation, at constant stress fail at inordinately different times even under laboratory test conditions. In order to be able to estimate the life of power equipment, it is necessary to run long duration ageing experiments under accelerated stresses, to acquire and analyze insulation specific failure data. In the present work, Resin Impregnated Paper (RIP) a relatively new insulation system of choice used in transformer bushings, is taken as an example. The failure data has been processed using proven statistical methods, both graphical and analytical. The physical model governing insulation failure at constant accelerated stress has been assumed to be based on temperature dependent inverse power law model.

Unified Taxonomy for Reference Ontology of Shape Features in Product Model

This paper presents a unified taxonomy of shape features. Such taxonomy is required to construct ontologies to address heterogeneity in product/shape models. Literature provides separate classifications for volumetric, deformation and free-form surface features. The unified taxonomy proposed allows classification, representation and extraction of shape features in a product model. The novelty of the taxonomy is that the classification is based purely on shape entities and therefore it is possible to automatically extract the features from any shape model. This enables the use of this taxonomy to build reference ontology.

Average Modelling of a Voltage Source Inverter with Dead-Time in a Synchronous Reference Frame

Voltage source inverters are an integral part of renewable power sources and smart grid systems. Computationally efficient and fairly accurate models for the voltage source inverter are required to carry out extensive simulation studies on complex power networks. Accuracy requires that the effect of dead-time be incorporated in the inverter model. The dead-time is essentially a short delay introduced between the gating pulses to the complementary switches in an inverter leg for the safety of power devices. As the modern voltage source inverters switch at fairly high frequencies, the dead-time significantly influences the output fundamental voltage. Dead-time also causes low-frequency harmonic distortion and is hence important from a power quality perspective. This paper studies the dead-time effect in a synchronous dq reference frame, since dynamic studies and controller design are typically carried out in this frame of reference. For the sake of computational efficiency, average models are derived, incorporating the dead-time effect, in both RYB and dq reference frames. The average models are shown to consume less computation time than their corresponding switching models, the accuracies of the models being comparable. The proposed average synchronous reference frame model, including effect of dead-time, is validated through experimental results.

Skip Decision and Reference Frame Selection for Low-Complexity H.264/AVC Surveillance Video Coding

H. 264/advanced video coding surveillance video encoders use the Skip mode specified by the standard to reduce bandwidth. They also use multiple frames as reference for motion-compensated prediction. In this paper, we propose two techniques to reduce the bandwidth and computational cost of static camera surveillance video encoders without affecting detection and recognition performance. A spatial sampler is proposed to sample pixels that are segmented using a Gaussian mixture model. Modified weight updates are derived for the parameters of the mixture model to reduce floating point computations. A storage pattern of the parameters in memory is also modified to improve cache performance. Skip selection is performed using the segmentation results of the sampled pixels. The second contribution is a low computational cost algorithm to choose the reference frames. The proposed reference frame selection algorithm reduces the cost of coding uncovered background regions. We also study the number of reference frames required to achieve good coding efficiency. Distortion over foreground pixels is measured to quantify the performance of the proposed techniques. Experimental results show bit rate savings of up to 94.5% over methods proposed in literature on video surveillance data sets. The proposed techniques also provide up to 74.5% reduction in compression complexity without increasing the distortion over the foreground regions in the video sequence.

CLAP: A web-server for automatic classification of proteins with special reference to multi-domain proteins

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/.

A zero charge-pump mismatch current tracking loop for reference spur reduction in PLLs

The charge-pump (CP) mismatch current is a dominant source of static phase error and reference spur in the nano-meter CMOS PLL implementations due to its worsened channel length modulation effect. This paper presents a charge-pump (CP) mismatch current reduction technique utilizing an adaptive body bias tuning of CP transistors and a zero CP mismatch current tracking PLL architecture for reference spur suppression. A chip prototype of the proposed circuit was implemented in 0.13 mu m CMOS technology. The frequency synthesizer consumes 8.2 mA current from a 13 V supply voltage and achieves a phase noise of -96.01 dBc/Hz @ 1 MHz offset from a 2.4 GHz RF carrier. The charge-pump measurements using the proposed calibration technique exhibited a mismatch current of less than 0.3 mu A (0.55%) over the VCO control voltage range of 0.3-1.0 V. The closed loop measurements show a minimized static phase error of within +/- 70 ps and a similar or equal to 9 dB reduction in reference spur level across the PLL output frequency range 2.4-2.5 GHz. The presented CP calibration technique compensates for the DC current mismatch and the mismatch due to channel length modulation effect and therefore improves the performance of CP-PLLs in nano-meter CMOS implementations. (C) 2015 Elsevier Ltd. All rights reserved.

Timing Calculations for a General N-Level Dodecagonal Space Vector Structure Using Only Reference Phase Voltages

Multilevel inverters with dodecagonal (12-sided polygon) voltage space vector (SV) structures have advantages like extension of linear modulation range, elimination of fifth and seventh harmonics in phase voltages and currents for the full modulation range including extreme 12-step operation, reduced device voltage ratings, lesser dv/dt stresses on devices and motor phase windings resulting in lower EMI/EMC problems, and lower switching frequency-making it more suitable for high-power drive applications. This paper proposes a simple method to obtain pulsewidth modulation (PWM) timings for a dodecagonal voltage SV structure using only sampled reference voltages. In addition to this, a carrier-based method for obtaining the PWM timings for a general N-level dodecagonal structure is proposed in this paper for the first time. The algorithm outputs the triangle information and the PWM timing values which can be set as the compare values for any carrier-based hardware PWM module to obtain SV PWM like switching sequences. The proposed method eliminates the need for angle estimation, computation of modulation indices, and iterative search algorithms that are typical in multilevel dodecagonal SV systems. The proposed PWM scheme was implemented on a five-level dodecagonal SV structure. Exhaustive simulation and experimental results for steady-state and transient conditions are presented to validate the proposed method.

Correlative reference model and molecular dynamics simulation of dislocation emission process

A correlative reference model for computer molecular dynamics simulations is proposed. Based on this model, a flexible displacement boundary scheme is introduced and the dislocations emitted from a crack tip can continuously pass through the border of the inner discrete atomic region and pile up at the outer continuum region. The effect of the emitted dislocations within the plastic zone on the inner atomistic region can be clearly demonstrated. The simulations for a molybdinum crystal show that a full dislocation in a bcc crystal is dissociated into three partial dislocations and interaction between the crack and the emitted dislocations results in gradual decrease of the local stress intensity factor.

La contribución del matrimonio al bien común : perspectivas y desafíos

Resumen: Este artículo se propone estudiar la vinculación entre matrimonio y bien común, a partir del debate en la Argentina de la ley 26.618 de legalización de las uniones homosexuales como matrimonio y de los lineamientos propuestos por Benedicto XVI en Caritas in Veritate. Se advierte una claudicación en la búsqueda del bien común que obedece a diferentes factores, sobre todo el relativismo cultural. Se propone una noción de bien común que respeta la dignidad de la persona y su dimensión social y se consideran las contribuciones del matrimonio al bien común. Se advierte cómo la ley 26.618 concede a las uniones de personas del mismo sexo beneficios propios del matrimonio entre varón y mujer sin que se cumplan las funciones sociales de esa institución. También se proponen algunas condiciones de la vida social que favorecen al matrimonio para que así contribuya al bien común, con especial referencia al ámbito de la legislación, las políticas públicas, los medios de comunicación, la empresa y el mundo del trabajo y la ciencia y la tecnología. Finalmente, se consideran los obstáculos que surgieron en el reciente debate legislativo por la aparición de un laicismo militante y la contribución de las religiones al bien común desde una sana laicidad en esta materia.

Reference Points and Optimal Management in Stochastic Age-Structured Fisheries Models

The purpose of this article is to characterize dynamic optimal harvesting trajectories that maximize discounted utility assuming an age-structured population model, in the same line as Tahvonen (2009). The main novelty of our study is that uses as an age-structured population model the standard stochastic cohort framework applied in Virtual Population Analysis for fish stock assessment. This allows us to compare optimal harvesting in a discounted economic context with standard reference points used by fisheries agencies for long term management plans (e.g. Fmsy). Our main findings are the following. First, optimal steady state is characterized and sufficient conditions that guarantees its existence and uniqueness for the general case of n cohorts are shown. It is also proved that the optimal steady state coincides with the traditional target Fmsy when the utility function to be maximized is the yield and the discount rate is zero. Second, an algorithm to calculate the optimal path that easily drives the resource to the steady state is developed. And third, the algorithm is applied to the Northern Stock of hake. Results show that management plans based exclusively on traditional reference targets as Fmsy may drive fishery economic results far from the optimal.

Analysis of the legislative framework in the Brazilian policymaking process

Analisa os aspectos da estrutura política brasileira que contribuem para falhas nos processos decisórios e ineficácia nos resultados finais de políticas de governo, com ênfase nos problemas institucionais do poder legislativo. Aborda os seguintes tópicos: fragmentação do sistema partidário, infidelidade partidária, modelo de federalismo, preenchimento de cargos públicos, larga utilização de medidas provisórias, disfunções do processo legislativo.

Democracia eletrônica para quem? : Quem são, o que querem e como os cidadãos avaliam o portal da Câmara dos Deputados

A dissertação busca responder em que medida todas as possibilidades de interação ofertadas pelo Portal da Câmara dos Deputados atendem às necessidades de interação política dos cidadãos que utilizam estes novos canais. Quem são os usuários destas novas ferramentas? Qual a avaliação que eles fazem destes novos canais? Qual é a opinião deles sobre as possibilidades de participação eletrônica? O principal aspecto teórico abordado nesta dissertação é a seguinte discussão: a internet replica formas de participação tradicionais ou é realmente capaz de fazer com que mais cidadãos, incluindo aqueles que estão alheios e desinteressados, participem? Essas questões foram direcionadas ao Portal da Câmara dos Deputados do Brasil, que, ao longo dos últimos anos, soube adaptar-se e promover um espaço de amplo acesso a informações legislativas, com capacidade de contato e interação entre o cidadão e o seu representante e é considerado, atualmente, o melhor portal legislativo da América do Sul. A dissertação utilizou duas metodologias distintas. A primeira consistiu em analisar as estatísticas de acesso ao Portal, identificando assim os padrões de acesso: os sites de referência e os caminhos de busca através dos quais se chega ao Portal. A segunda consistiu na condução de um Web Survey para coletar a opinião dos usuários. O questionário aplicado teve como objetivo coletar avaliações das ferramentas disponibilizadas pelo Portal, identificar o perfil dos usuários e compreender-lhes o comportamento político no mundo off-line. Um dos principais achados é o de que a Democracia Eletrônica desenvolvida pelo Portal da Câmara dos Deputados tem servido mais aos profissionais da política que ao cidadão comum. Mas, mesmo assim, o cidadão comum, interessado em buscar participação, contato e interação com os atores políticos, está procurando essas ferramentas on-line. Palavras chaves: Democracia Eletrônica, Câmara dos Deputados, pesquisa on-line, estatísticas de acesso.