Simplified implementation of space vector PWM strategies for a three level inverter

Space vector based PWM strategies for three-level inverters have a broader choice of switching sequences to generate the required reference vector than triangle comparison based PWM techniques. However, space vector based PWM involves numerous steps which are computationally intensive. A simplified algorithm is proposed here, which is shown to reduce the computation time significantly. The developed algorithm is used to implement synchronous and asynchronous conventional space vector PWM, synchronized modified space vector PWM and an asynchronous advanced bus-clamping PWM technique on a low-cost dsPIC digital controller. Experimental results are presented for a comparative evaluation of the performance of different PWM methods.

Sequential alternating proximal method for scalable sparse structural SVMs

Structural Support Vector Machines (SSVMs) have recently gained wide prominence in classifying structured and complex objects like parse-trees, image segments and Part-of-Speech (POS) tags. Typical learning algorithms used in training SSVMs result in model parameters which are vectors residing in a large-dimensional feature space. Such a high-dimensional model parameter vector contains many non-zero components which often lead to slow prediction and storage issues. Hence there is a need for sparse parameter vectors which contain a very small number of non-zero components. L1-regularizer and elastic net regularizer have been traditionally used to get sparse model parameters. Though L1-regularized structural SVMs have been studied in the past, the use of elastic net regularizer for structural SVMs has not been explored yet. In this work, we formulate the elastic net SSVM and propose a sequential alternating proximal algorithm to solve the dual formulation. We compare the proposed method with existing methods for L1-regularized Structural SVMs. Experiments on large-scale benchmark datasets show that the proposed dual elastic net SSVM trained using the sequential alternating proximal algorithm scales well and results in highly sparse model parameters while achieving a comparable generalization performance. Hence the proposed sequential alternating proximal algorithm is a competitive method to achieve sparse model parameters and a comparable generalization performance when elastic net regularized Structural SVMs are used on very large datasets.

Support vector machine based high speed protection relay for EHV/UHV transmission line

This paper presents a fast and accurate relaying technique for a long 765kv UHV transmission line based on support vector machine. For a long EHV/UHV transmission line with large distributed capacitance, a traditional distance relay which uses a lumped parameter model of the transmission line can cause malfunction of the relay. With a frequency of 1kHz, 1/4th cycle of instantaneous values of currents and voltages of all phases at the relying end are fed to Support Vector Machine(SVM). The SVM detects fault type accurately using 3 milliseconds of post-fault data and reduces the fault clearing time which improves the system stability and power transfer capability. The performance of relaying scheme has been checked with a typical 765kV Indian transmission System which is simulated using the Electromagnetic Transients Program(EMTP) developed by authors in which the distributed parameter line model is used. More than 15,000 different short circuit fault cases are simulated by varying fault location, fault impedance, fault incidence angle and fault type to train the SVM for high speed accurate relaying. Simulation studies have shown that the proposed relay provides fast and accurate protection irrespective of fault location, fault impedance, incidence time of fault and fault type. And also the proposed scheme can be used as augmentation for the existing relaying, particularly for Zone-2, Zone-3 protection.

Bilateral smoothing of gradient vector field and application to image segmentation

Medical image segmentation finds application in computer-aided diagnosis, computer-guided surgery, measuring tissue volumes, locating tumors, and pathologies. One approach to segmentation is to use active contours or snakes. Active contours start from an initialization (often manually specified) and are guided by image-dependent forces to the object boundary. Snakes may also be guided by gradient vector fields associated with an image. The first main result in this direction is that of Xu and Prince, who proposed the notion of gradient vector flow (GVF), which is computed iteratively. We propose a new formalism to compute the vector flow based on the notion of bilateral filtering of the gradient field associated with the edge map - we refer to it as the bilateral vector flow (BVF). The range kernel definition that we employ is different from the one employed in the standard Gaussian bilateral filter. The advantage of the BVF formalism is that smooth gradient vector flow fields with enhanced edge information can be computed noniteratively. The quality of image segmentation turned out to be on par with that obtained using the GVF and in some cases better than the GVF.

Some questions on integral geometry on noncompact symmetric spaces of higher rank

Let be a noncompact symmetric space of higher rank. We consider two types of averages of functions: one, over level sets of the heat kernel on and the other, over geodesic spheres. We prove injectivity results for functions in which extend the results in Pati and Sitaram (Sankya Ser A 62:419-424, 2000).

A cyclic peptide mimic of an RNA recognition motif of human La protein is a potent inhibitor of hepatitis C virus

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.

The precision with which single cells of Dictyostelium discoideum can locate a source of cyclic AMP

When stimulated by a point source of cyclic AMP, a starved amoeba of Dictyostelium discoideum responds by putting out a hollow balloon-like membrane extension followed by a pseudopod. The effect of the stimulus is to influence the position where either of these protrusions is made on the cell rather than to cause them to be made. Because the pseudopod forms perpendicular to the cell surface, its location is a measure of the precision with which the cell can locate the cAMP source. Cells beyond 1 h of starvation respond non-randomly with a precision that improves steadily thereafter. A cell that is starved for 1-2 h can locate the source accurately 43% of the time; and if starved for 6-7 h, 87% of the time. The response always has a high scatter; population-level heterogeneity reflects stochasticity in single cell behaviour. From the angular distribution of the response its maximum information content is estimated to be 2-3 bits. In summary, we quantitatively demonstrate the stochastic nature of the directional response and the increase in its accuracy over time.

A study on the usefulness of Support Vector Machines for the realtime computational simulation of soft biological organs

Realistic and realtime computational simulation of soft biological organs (e.g., liver, kidney) is necessary when one tries to build a quality surgical simulator that can simulate surgical procedures involving these organs. Since the realistic simulation of these soft biological organs should account for both nonlinear material behavior and large deformation, achieving realistic simulations in realtime using continuum mechanics based numerical techniques necessitates the use of a supercomputer or a high end computer cluster which are costly. Hence there is a need to employ soft computing techniques like Support Vector Machines (SVMs) which can do function approximation, and hence could achieve physically realistic simulations in realtime by making use of just a desktop computer. Present work tries to simulate a pig liver in realtime. Liver is assumed to be homogeneous, isotropic, and hyperelastic. Hyperelastic material constants are taken from the literature. An SVM is employed to achieve realistic simulations in realtime, using just a desktop computer. The code for the SVM is obtained from [1]. The SVM is trained using the dataset generated by performing hyperelastic analyses on the liver geometry, using the commercial finite element software package ANSYS. The methodology followed in the present work closely follows the one followed in [2] except that [2] uses Artificial Neural Networks (ANNs) while the present work uses SVMs to achieve realistic simulations in realtime. Results indicate the speed and accuracy that is obtained by employing the SVM for the targeted realistic and realtime simulation of the liver.

Multiple molecular alterations in phosphodegrons 1-3 within AAV2 capsid demonstrates higher hepatic gene transfer efficiency

The success of AAV2 mediated hepatic gene transfer in human trials for diseases such as hemophilia has been hampered by a combination of low transduction efficiency and a robust immune response directed against these vectors. We have previously shown that AAV2 is targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal degradation machinery and modification of the serine(S)/threonine(T) kinase and lysine(K) targets on AAV capsid is beneficial. Thus targeted single mutations of S/T>A(S489A, S498A, T251A) and K>R (K532R) improved the efficiency of gene transfer in vivo as compared to wild type (WT)-AAV2 vectors (∼6-14 fold). In the present study, we evaluated if combined alteration of the phosphodegrons (PD), which are the phosphorylation sites recognized as degradation signals by ubiquitin ligases, improves further the gene transfer efficiency. Thus, we generated four multiple mutant vectors (PD: 1+3, S489A+K532R, PD: 1+3, S489A+K532R together with T251 residue which did not lie in any of the phosphodegrons but had shown increased transduction efficiency compared to the WT-AAV2 vector (∼6 fold) and was also conserved in 9 out of 10 AAV serotypes (AAV 1 to 10), PD: 1+3, S489A+K532R+S498A and a fourth combination of PD: 3, K532R+T251. We then evaluated them in vitro and in vivo and compared their gene transfer efficiency with either the WT-AAV2 or the best single mutant S489A-AAV2 vector. The novel multiple mutations on the AAV2 capsid did not affect the overall vector packaging efficiency. All the multiple AAV2 mutants showed superior transduction efficiency in HeLa cells in vitro when compared to either the WT (62-72% Vs 21%) or the single mutant S489A (62-72% Vs 50%) AAV2 vectors as demonstrated by FACS analysis (Fig. 1A). On hepatic gene transfer with 5x10^10 vgs per animal in C57BL/6 mice, all the multiple mutants showed increased transgene expression compared to either the WT-AAV2 (∼15-23 fold) or the S489A single mutant vector (∼2-3 fold) (Fig.1B and C). These novel multiple mutant AAV2 vectors also showed higher vector copy number in murine hepatocytes 4 weeks post transduction, as compared to the WT-AAV2 (∼5-6 Vs 1.4 vector copies/diploid genome) and further higher when compared to the single mutant S489A(∼5-6 fold Vs 3.8 fold) (Fig.1D). Further ongoing studies will demonstrate the therapeutic benefit of one or more of the multiple mutants vectors in preclinical models of hemophilia.

A novel adeno-associated virus serotype (AAV)-8 capsid mutant improves human coagulation factor IX expression in vivo

Recombinant AAV-8 vectors have shown significant promise for hepatic gene therapy of hemophilia B. However, the theme of AAV vector dose dependent immunotoxicity seen with AAV2 vectors earlier seem to re-emerge with AAV8 vectors as well. It is therefore important to develop novel AAV8 vectors that provide enhanced gene expression at significantly less vector doses. We hypothesized that AAV8 during its intracellular trafficking, are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal degradation machinery and modification of specific serine/threonine kinase or ubiquitination targets on AAV8 capsid (Fig.1A) may improve its transduction efficiency. To test this, point mutations at specific serine (S)/threonine (T) > alanine (A) or lysine (K)>arginine (R) residues were generated on AAV8 capsid. scAAV8-EGFP vectors containing the wild-type (WT) and each one of the 5 S/T/K-mutant(S276A, S501A, S671A, T251A and K137R) capsids were evaluated for their liver transduction efficiency at a dose of 5 X 1010 vgs/ animal in C57BL/6 mice in vivo. The best performing mutant was found to be the K137R vector in terms of either the gene expression (46-fold) or the vector copy numbers in the hepatocytes (22-fold) compared to WT-AAV8 (Fig.1B). The K137R-AAV8 vector that showed significantly decreased ubiquitination of the viral capsid had reduced activation of markers of innate immune response [IL-6, IL-12, tumor necrosis factor α, Kupffer cells and TLR-9]. In addition, animals injected with the K137R mutant also demonstrated decreased (2-fold) levels of cross-neutralizing antibodies when compared to animals that received the WT-AAV8 vector. To study further the utility of the novel AAV8-K137R mutant in a therapeutic setting, we delivered human coagulation factor IX (h.FIX) under the control of liver specific promoters (LP1 or hAAT) at two different doses (2.5x10^10 and 1x10^11 vgs per mouse) in 8-12 weeks old male C57BL/6 mice. As can be seen in Fig.1C/D, the circulating levels of h.FIX were higher in all the K137R-AAV8 treated groups as compared to the WT-AAV8 treated groups either at 2 weeks (62% vs 37% for hAAT constructs and 47% vs 21% for LP1 constructs) or 4 weeks (78% vs 56% for hAAT constructs and 64% vs 30% for LP1 constructs) post hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel vector for potential gene therapy of hemophilia B.

Cyclic AMP-dependent protein lysine acylation in mycobacteria regulates fatty acid and propionate metabolism

Acetylation of lysine residues is a posttranslational modification that is used by both eukaryotes and prokaryotes to regulate a variety of biological processes. Here we identify multiple substrates for the cAMP-dependent protein lysine acetyltransferase from Mycobacterium tuberculosis (KATmt). We demonstrate that a catalytically important lysine residue in a number of FadD (fatty acyl CoA synthetase) enzymes is acetylated by KATmt in a cAMP-dependent manner and that acetylation inhibits the activity of FadD enzymes. A sirtuin-like enzyme can deacetylate multiple FadDs, thus completing the regulatory cycle. Using a strain deleted for the KATmt ortholog in Mycobacterium bovis Bacillus Calmette-Guerin (BCG), we show for the first time that acetylation is dependent on intracellular cAMP levels. KATmt can utilize propionyl CoA as a substrate and, therefore, plays a critical role in alleviating propionyl CoA toxicity in mycobacteria by inactivating acyl CoA synthetase (ACS). The precision by which mycobacteria can regulate the metabolism of fatty acids in a cAMP-dependent manner appears to be unparalleled in other biological organisms and is ideally suited to adapt to the complex environment that pathogenic mycobacteria experience in the host.