Efficient Dendrimer-DNA Complexation and Gene Delivery Vector Properties of Nitrogen-Core Poly(propyl ether imine) Dendrimer in Mammalian Cells

Dendrimers as vectors for gene delivery were established, primarily by utilizing few prominent dendrimer types so far. We report herein studies of DNA complexation efficacies and gene delivery vector properties of a nitrogen-core poly(propyl ether imine) (PETIM) dendrimer, constituted with 22 tertiary amine internal branches and 24 primary amines at the periphery. The interaction of the dendrimer with pEGFPDNA was evaluated through UV-vis, circular dichroism (CD) spectral studies, ethidium bromide fluorescence emission quenching, thermal melting, and gel retardation assays, from which most changes to DNA structure during complexation was found to occur at a weight ratio of dendrimer:DNA similar to 2:1. The zeta potential measurements further confirmed this stoichiometry at electroneutrality. The structure of a DNA oligomer upon dendrimer complexation was simulated through molecular modeling and the simulation showed that the dendrimer enfolded DNA oligomer along both major and minor grooves, without causing DNA deformation, in 1:1 and 2:1 dendrimer-to-DNA complexes. Atomic force microscopy (AFM) studies on dendrimer-pEGFP DNA complex showed an increase in the average z-height as a result of dendrimers decorating the DNA, without causing a distortion of the DNA structure. Cytotoxicity studies involving five different mammalian cell lines, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) assay, reveal the dendrimer toxicity profile (IC50) values of similar to 400-1000 mu g mL(-1), depending on the cell line tested. Quantitative estimation, using luciferase assay, showed that the gene transfection was at least 100 times higher when compared to poly(ethylene imine) branched polymer, having similar number of cationic sites as the dendrimer. The present study establishes the physicochemical behavior of new nitrogen-core PETIM dendrimer-DNA complexes, their lower toxicities, and efficient gene delivery vector properties.

A Novel Design Method for SOGI-PLL for Minimum Settling Time and Low Unit Vector Distortion

Phase-locked loops (PLLs) are necessary in grid connected systems to obtain information about the frequency, amplitude and phase of the grid voltage. In stationary reference frame control, the unit vectors of PLLs are used for reference generation. It is important that the PLL performance is not affected significantly when grid voltage undergoes amplitude and frequency variations. In this paper, a novel design for the popular single-phase PLL topology, namely the second-order generalized integrator (SOGI) based PLL is proposed which achieves minimum settling time during grid voltage amplitude and frequency variations. The proposed design achieves a settling time of less than 27.7 ms. This design also ensures that the unit vectors generated by this PLL have a steady state THD of less than 1% during frequency variations of the grid voltage. The design of the SOGI-PLL based on the theoretical analysis is validated by experimental results.

A New Voltage Stability Index based on the Tangent Vector of the Power Flow Jacobian

This paper presents a new voltage stability index based on the tangent vector of the power flow jacobian. This index is capable of providing the relative vulnerability information of the system buses from the point of view of voltage collapse. In an effort to compare this index with a similar index, the popular voltage stability index L is studied and it is shown through system studies that the L index is not a very consistent indicator of the voltage collapse point of the system but is only a reasonable indicator of the vulnerability of the system buses to voltage collapse. We also show that the new index can be used in the voltage stability analysis of radial systems which is not possible with the L index. This is a significant result of this investigation since there is a lot of contemporary interest in distributed generation and microgrids which are by and large radial in nature. Simulation results considering several test systems are provided to validate the results and the computational needs of the proposed scheme is assessed in comparison with other schemes

Space-Vector-Based Hybrid Pulsewidth Modulation Techniques for a Three-Level Inverter

Novel switching sequences have been proposed recently for a neutral-point-clamped three-level inverter, controlled effectively as an equivalent two-level inverter. It is shown that the four novel sequences can be grouped into two pairs of sequences. Using each pair of sequences, a hybrid pulsewidth modulation (PWM) technique is proposed, which deploys the two sequences in appropriate spatial regions to reduce the current ripple. Further, a third hybrid PWM technique is proposed which uses all the five sequences (including the conventional sequence) in appropriate spatial regions. Each proposed hybrid PWM is shown, both analytically and experimentally, to outperform its constituent PWM methods in terms of harmonic distortion. In particular, the third proposed hybrid PWM reduces the total harmonic distortion considerably at low- and high-speed ranges of a constant volts-per-hertz induction motor drive, compared to centered space vector PWM.

A Nearly Constant Switching Frequency Current Error Space Vector Based Hysteresis Controller for an IM Drive with 12-sided Polygonal Voltage Space Vectors

In this paper, a current error space vector (CESV) based hysteresis controller for a 12-sided polygonal voltage space vector inverter fed induction motor (IM) drive is proposed, for the first time. An open-end winding configuration is used for the induction motor. The proposed controller uses parabolic boundary with generalized vector selection logic for all sectors. The drive scheme is first studied with a space vector based PWM (SVPWM) control and from this the current error space phasor boundary is obtained. This current error space phasor boundary is approximated with four parabolas and then the system is run with space phasor based hysteresis PWM controller by limiting the CESV within the parabolic boundary. The proposed controller has increased modulation range, absence of 5th and 7th order harmonics for the entire modulation range, nearly constant switching frequency, fast dynamic response with smooth transition to the over modulation region and a simple controller implementation.

Multi-site downscaling of maximum and minimum daily temperature using support vector machine

Climate change impact assessment studies involve downscaling large-scale atmospheric predictor variables (LSAPVs) simulated by general circulation models (GCMs) to site-scale meteorological variables. This article presents a least-square support vector machine (LS-SVM)-based methodology for multi-site downscaling of maximum and minimum daily temperature series. The methodology involves (1) delineation of sites in the study area into clusters based on correlation structure of predictands, (2) downscaling LSAPVs to monthly time series of predictands at a representative site identified in each of the clusters, (3) translation of the downscaled information in each cluster from the representative site to that at other sites using LS-SVM inter-site regression relationships, and (4) disaggregation of the information at each site from monthly to daily time scale using k-nearest neighbour disaggregation methodology. Effectiveness of the methodology is demonstrated by application to data pertaining to four sites in the catchment of Beas river basin, India. Simulations of Canadian coupled global climate model (CGCM3.1/T63) for four IPCC SRES scenarios namely A1B, A2, B1 and COMMIT were downscaled to future projections of the predictands in the study area. Comparison of results with those based on recently proposed multivariate multiple linear regression (MMLR) based downscaling method and multi-site multivariate statistical downscaling (MMSD) method indicate that the proposed method is promising and it can be considered as a feasible choice in statistical downscaling studies. The performance of the method in downscaling daily minimum temperature was found to be better when compared with that in downscaling daily maximum temperature. Results indicate an increase in annual average maximum and minimum temperatures at all the sites for A1B, A2 and B1 scenarios. The projected increment is high for A2 scenario, and it is followed by that for A1B, B1 and COMMIT scenarios. Projections, in general, indicated an increase in mean monthly maximum and minimum temperatures during January to February and October to December.

Survey of vector-like fermion extensions of the Standard Model and their phenomenological implications

With the renewed interest in vector-like fermion extensions of the Standard Model, we present here a study of multiple vector-like theories and their phenomenological implications. Our focus is mostly on minimal flavor conserving theories that couple the vector-like fermions to the SM gauge fields and mix only weakly with SM fermions so as to avoid flavor problems. We present calculations for precision electroweak and vector-like state decays, which are needed to investigate compatibility with currently known data. We investigate the impact of vector-like fermions on Higgs boson production and decay, including loop contributions, in a wide variety of vector-like extensions and their parameter spaces.

Space vector based modulation scheme for reducing capacitor RMS current in three-level diode-clamped inverter

The DC capacitor is an important component in a voltage source inverter.The RMS current flowing through the capacitor determines the capacitor size and losses. The losses, in turn, influence the capacitor life. This paper proposes a space vector based modulation strategy for reducing the capacitor RMS current in a three-level diode-clamped inverter. An analytical closed-form expression is derived for the DC capacitor RMS current with the proposed PWM strategy. The analytical expression is validated through simulations and also experimentally. Theoretical and experimental results are presented, comparing the proposed strategy with conventional space vector PWM (CSVPWM). It is shown that the proposed strategy reduces the capacitor RMS current significantly at high modulation indices and high power factors. (C) 2014 Elsevier B.V. All rights reserved.

Space-Vector-Based Hybrid PWM Technique to Reduce Peak-to-Peak Torque Ripple in Induction Motor Drives

Special switching sequences involving division of active state time are used in space-vector-based generation of pulse width modulation (PWM) waveforms. This paper proposes a hybrid PWM technique which is a combination of the conventional and special switching sequences. The proposed hybrid PWM technique reduces the peak-to-peak torque ripple at high speeds of an induction motor drive. Supporting simulation and experimental results are presented from a closed-loop controlled motor drive.

Acoustic Noise Characterization of Space-Vector Modulated Induction Motor Drives-An Experimental Approach

This paper presents an experimental procedure to determine the acoustic and vibration behavior of an inverter-fed induction motor based on measurements of the current spectrum, acoustic noise spectrum, overall noise in dB, and overall A-weighted noise in dBA. Measurements are carried out on space-vector modulated 8-hp and 3-hp induction motor drives over a range of carrier frequencies at different modulation frequencies. The experimental data help to distinguish between regions of high and low acoustic noise levels. The measurements also bring out the impact of carrier frequency on the acoustic noise. The sensitivity of the overall noise to carrier frequency is indicative of the relative dominance of the high-frequency electromagnetic noise over mechanical and aerodynamic components of noise. Based on the measured current and acoustic noise spectra, the ratio of dynamic deflection on the stator surface to the product of fundamental and harmonic current amplitudes is obtained at each operating point. The variation of this ratio of deflection to current product with carrier frequency indicates the resonant frequency clearly and also gives a measure of the amplification of vibration at frequencies close to the resonant frequency. This ratio is useful to predict the magnitude of acoustic noise corresponding to significant time-harmonic currents flowing in the stator winding.

Exploring Viral Phenomenon as an Innovative Trajectory

The viral phenomenon has garnered a great deal of attention in the recent years. Although evidence of viral success exists the underlying factors leading to the phenomenon and its measurement still remains a grey area which needs to be explored. The viral phenomenon for a product or information and its distinction based on growth curve trajectory has not been rigorously explored in the previous works. This paper aims to understand the viral phenomenon that makes products or information go viral. The viral phenomenon trajectories that distinguish the viral from a non-viral phenomenon are demonstrated. The curve fitting methodology for viral phenomenon is adopted which has not been looked into in the previous works. TED talks are analyzed to understand the diffusion pattern, essentially one or more spike, within a time period. Insights drawn indicate the characteristic viral growth trajectories and its implication on innovation.

Viruses and viral proteins

For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes.

Targeted Modifications in Adeno-Associated Virus Serotype 8 Capsid Improves Its Hepatic Gene Transfer Efficiency In Vivo

Recombinant adeno-associated virus vectors based on serotype 8 (AAV8) have shown significant promise for liver-directed gene therapy. However, to overcome the vector dose dependent immunotoxicity seen with AAV8 vectors, it is important to develop better AAV8 vectors that provide enhanced gene expression at significantly low vector doses. Since it is known that AAV vectors during intracellular trafficking are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal machinery, we modified specific serine/threonine kinase or ubiquitination targets on the AAV8 capsid to augment its transduction efficiency. Point mutations at specific serine (S)/threonine (T)/lysine (K) residues were introduced in the AAV8 capsid at the positions equivalent to that of the effective AAV2 mutants, generated successfully earlier. Extensive structure analysis was carried out subsequently to evaluate the structural equivalence between the two serotypes. scAAV8 vectors with the wild-type (WT) and each one of the S/T -> Alanine (A) or K-Arginine (R) mutant capsids were evaluated for their liver transduction efficiency in C57BL/6 mice in vivo. Two of the AAV8-S -> A mutants (S279A and S671A), and a K137R mutant vector, demonstrated significantly higher enhanced green fluorescent protein (EGFP) transcript levels (similar to 9- to 46-fold) in the liver compared to animals that received WT-AAV8 vectors alone. The best performing AAV8 mutant (K137R) vector also had significantly reduced ubiquitination of the viral capsid, reduced activation of markers of innate immune response, and a concomitant two-fold reduction in the levels of neutralizing antibody formation in comparison to WT-AAV8 vectors. Vector bio-distribution studies revealed that the K137R mutant had a significantly higher and preferential transduction of the liver (106 vs. 7.7 vector copies/mouse diploid genome) when compared to WT-AAV8 vectors. To further study the utility of the K137R-AAV8 mutant in therapeutic gene transfer, we delivered human coagulation factor IX (h. FIX) under the control of liver-specific promoters (LP1 or hAAT) into C57BL/6 mice. The circulating levels of h. FIX: Ag were higher in all the K137R-AAV8 treated groups up to 8 weeks post-hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel AAV8 vectors for potential gene therapy of hemophilia B.

Low-Order Harmonic Suppression for Open-End Winding IM With Dodecagonal Space Vector Using a Single DC-Link Supply

This paper proposes a technique to suppress low-order harmonics for an open-end winding induction motor drive for a full modulation range. One side of the machine is connected to a main inverter with a dc power supply, whereas the other inverter is connected to a capacitor from the other side. Harmonic suppression (with complete elimination of fifth- and seventh-order harmonics) is achieved by realizing dodecagonal space vectors using a combined pulsewidth modulation (PWM) control for the two inverters. The floating capacitor voltage is inherently controlled during the PWM operation. The proposed PWM technique is shown to be valid for the entire modulation range, including overmodulation and six-step mode of operation of the main inverter. Experimental results have been presented to validate the proposed technique.