Contrasting reactivity behaviour of the RuHCl(CO)(PNP)] complex with electrophilic reagents XOTf (X = H, CH3, Me3Si)

A new ruthenium pincer complex RuHCl(CO)(PNP)] (PNP = PhCH2N(CH2CH2PPh2)(2)) (1) was synthesized and characterized. The reactivity of complex 1 with electrophilic reagents XOTf (X = H, CH3, and Me3Si; OTf = CF3SO3) was studied by variable temperature NMR spectroscopy with an aim to observe and characterize sigma complexes of type Ru(eta(2)-HX)Cl(CO)(PNP)]OTf] (X = H (2), CH3 (3), Me3Si (4)). Reaction of complex 1 with HOTf resulted in the formation of the dihydrogen complex, Ru(eta(2)-H-2)Cl(CO)(PNP)OTf] (2). On the other hand, the reaction between complex 1 and MeOTf and Me3SiOTf resulted in the direct elimination of MeCl and Me3SiCl via a S(N)2 type of reaction without the intermediacy of the respective sigma complexes 3 and 4. This contrasting reactivity behaviour has been rationalized taking into consideration the approach of the relatively bulky electrophites CH3+ and Me3Si+ onto the hydride moiety of the ruthenium fragment, which is sterically hindered.

Effect of Zirconium on the Densification of Reactively Hot-Pressed Zirconium Carbide

Densification mechanisms involved during reactive hot pressing (RHP) of zirconium carbide (ZrC) have been studied. RHP has been carried out using zirconium (Zr) and graphite (C) powders in the molar ratios 1:0.5, 1:0.67, 1:0.8, and 1:1 at 40MPa, 800 degrees C-1200 degrees C for different durations. The volume fractions of phases formed, including porosity, are determined from the measured density and from Rietveld analysis. Increased densification with an increasing nonstoichiometry in carbon has been observed. Microstructural and X-ray diffraction observations coupled with the predictions of a model based on the constitutive laws governing plastic flow of zirconium suggest that the better densification of nonstoichiometric compositions arise from the higher amount of starting Zr and also the longer duration of its availability for plastic flow during RHP. Volume shrinkage due to reaction between Zr and C and the gradual elimination of the soft metal phase limit the final density achievable. Based on these observations, a two-step RHP carried out at 800 degrees C and 1200 degrees C leads to a better densification than a single RHP at 1200 degrees C.

Lipid coated mesoporous silica nanoparticles as an oral delivery system for targeting and treatment of intravacuolar Salmonella infections

Lipid coated mesoporous silica nanoparticle (L-MSN) were synthesized for oral delivery of ciprofloxacin for intracellular elimination of Salmonella pathogen. The particle size was found to be between 50-100 nm with a lipid coat of approximately 5 nm thickness. The lipid coating was achieved by sonication of liposomes with the MSN particles and evaluated by CLSMand FTIR studies. The L-MSN particles exhibited lower cytotoxicity compared to bare MSN particles. Ciprofloxacin, a fluoroquinolone antibiotic, loaded into the L-MSN particles showed enhanced antibacterial activity against free drug in in vitro assays. The lipid coat was found to aid in intravacuolar targeting of the drug cargo as observed by confocal microscopy studies. We also observed that a lower dose of antibiotic was sufficient to clear the pathogen from mice and increase their survivability using the L-MSN oral delivery system.

An Advanced Gate Driver for Insulated Gate Bipolar Transistors to Eliminate Dead-time Induced Distortions in Inverter Output

Dead-time is introduced between the gating signals to the top and bottom switches in a voltage source inverter (VSI) leg, to prevent shoot through fault due to the finite turn-off times of IGBTs. The dead-time results in a delay when the incoming device is an IGBT, resulting in error voltage pulses in the inverter output voltage. This paper presents the design, fabrication and testing of an advanced gate driver, which eliminates dead-time and consequent output distortion. Here, the gating pulses are generated such that the incoming IGBT transition is not delayed and shoot-through is also prevented. The various logic units of the driver card and fault tolerance of the driver are verified through extensive tests on different topologies such as chopper, half-bridge and full-bridge inverter, and also at different conditions of load. Experimental results demonstrate the improvement in the load current waveform quality with the proposed circuit, on account of elimination of dead-time.

Electronically nonadiabatic decomposition mechanisms of clusters of zinc and dimethylnitramine

Electronically nonadiabatic decomposition mechanisms of dimethylnitramine (DMNA) in presence of zinc metal clusters are explored. Complete active space self-consistent field (CASSCF) calculation is employed for DMNA-Zn and ONIOM (Our own N-layered integrated molecular orbital and molecular mechanics) methodology is coupled with CASSCF methodology for DMNA-Zn-10 cluster. Present computational results show that DMNA-Zn clusters undergo electronically nonadiabatic reactions, rendering nitro-nitrite isomerization followed by NO elimination. The overall reactions are also found to be highly exothermic in nature. This is the first report on electronically nonadiabatic decomposition pathways of DMNA-Zn-n neutral clusters. (C) 2014 Elsevier B.V. All rights reserved.

Medium-Voltage Drive for Induction Machine With Multilevel Dodecagonal Voltage Space Vectors With Symmetric Triangles

Multilevel inverters with dodecagonal (12-sided polygon) voltage space vector structure have advantages, such as complete elimination of fifth and seventh harmonics, reduction in electromagnetic interference, reduction in device voltage ratings, reduction of switching frequency, extension of linear modulation range, etc., making it a viable option for high-power medium-voltage drives. This paper proposes two power circuit topologies capable of generating multilevel dodecagonal voltage space vector structure with symmetric triangles (for the first time) with minimum number of dc-link power supplies and floating capacitor H-bridges. The first power topology is composed of two hybrid cascaded five-level inverters connected to either side of an open-end winding induction machine. Each inverter consists of a three-level neutral-point-clamped inverter, which is cascaded with an isolated H-bridge making it a five-level inverter. The second topology is for a normal induction motor. Both of these circuit topologies have inherent capacitor balancing for floating H-bridges for all modulation indexes, including transient operations. The proposed topologies do not require any precharging circuitry for startup. A simple pulsewidth modulation timing calculation method for space vector modulation is also presented in this paper. Due to the symmetric arrangement of congruent triangles within the voltage space vector structure, the timing computation requires only the sampled reference values and does not require any offline computation, lookup tables, or angle computation. Experimental results for steady-state operation and transient operation are also presented to validate the proposed concept.

Excited electronic state decomposition mechanisms of clusters of dimethylnitramine and aluminum

In this report, electronically non-adiabatic decomposition pathways of clusters of dimethylnitramine and aluminum (DMNA-Al and DMNA-Al-2) are discussed in comparison to isolated dimethylnitramine (DMNA). Electronically excited state processes of DMNA-Al and DMNA-Al-2 are explored using the complete active space self-consistent field (CASSCF) and the restricted active space self-consistent field (RASSCF) theories, respectively. Similar to the nitro-nitrite isomerization reaction pathway of DMNA, DMNA-Al-n clusters also exhibit isomerization pathway. However, it involves several other steps, such as, first Al-O bond dissociation, then N-N bond dissociation followed by isomerization and finally NO elimination. Furthermore, DMNA-Al-n clusters exhibit overall exothermic decomposition reaction pathway and isolated DMNA shows overall endothermic reaction channel.

Modifications in Trypsin Digestion Protocol for Increasing the Efficiency and Coverage

Standard trypsin digestion protocol of proteins followed by MALDI-MS analysis has been realized as an important tool for the identification and characterization of proteins. In this article, we proposed the elimination of the step of `staining/de-staining of gel pieces' in in-gel digestion protocol in order to improve the efficiency of trypsin digestion. Coomassie dye is known to interfere with digestion of proteins by trypsin and the procedure of staining-de-staining could result in loss of photoaffinity probe, post translational modifications and catalytic activities of enzymes. Further, we studied parameters like hydrophobicity and isoelectric point, and attempted to quantitatively relate it to the efficiency of trypsin digestion. We suggest that properties of proteins should be considered and trypsin digestion protocol should be appropriately modified as per sequence and other information.

Identification of key amino acid residues in the catalytic mechanism of diaminopropionate ammonialyase from Salmonella typhimurium

Diaminopropionate ammonialyase (DAPAL), a fold-typeII pyridoxal 5-phosphate-dependent enzyme, catalyzes the ,-elimination of diaminopropionate (DAP) to pyruvate and ammonia. DAPAL was able to utilize both d- and l-DAP as substrates with almost equal efficiency. Mutational analysis of functionally important residues such as Thr385, Asp125 and Asp194 was carried out to understand the mechanism by which the isomers are hydrolyzed. Further, the putative residues involved in the formation of disulfide bond Cys271 and Cys299 were also mutated. T385S, T385D sDAPAL were as active with dl-DAP as substrate as sDAPAL, whereas the later exhibited a threefold increase in catalytic efficiency with d-Ser as substrate. Further analysis of these mutants suggested that DAPAL might follow an anti-E-2 mechanism of catalysis that does not involve the formation of a quinonoid intermediate. Of the two mutants of Asp125, D125E showed complete loss of activity with d-DAP as substrate, whereas the reaction with l-DAP was not affected significantly, demonstrating that Asp125 was essential for abstraction of protons from the d-isomer. By contrast, mutational analysis of Asp194 showed that the residue may not be directly involved in proton abstraction from l-DAP. sDAPAL does not form a disulfide bond in solution, although the position of Cys299 and Cys271 in the modeled structure of sDAPAL favored the formation of a disulfide bond. Further, unlike eDAPAL, sDAPAL could be activated by monovalent cations. Mutation of the cysteine residues showed that Cys271 may be involved in coordinating the monovalent cation, as observed in the case of other fold-typeII enzymes.

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising ``multiantigen'' vaccine that elicits robust CMI. IMPORTANCE Since their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is currently available, and treatment is costly and often results in side effects, limiting the number of patients who are treated. Despite recent advances in treatment, prevention remains the key to efficient control and elimination of this virus. Here, we describe a novel DNA vaccine against hepatitis C virus that is capable of inducing robust cell-mediated immune responses in mice and is a promising vaccine candidate for humans.

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.

Study of Wrist Pulse Signals Using a Bi-Modal Gaussian Model

Wrist pulse signals contain important information about the health of a person and hence diagnosis based on pulse signals has assumed great importance. In this paper we demonstrate the efficacy of a two term Gaussian model to extract information from pulse signals. Results have been obtained by conducting experiments on several subjects to record wrist pulse signals for the cases of before exercise and after exercise. Parameters have been extracted from the recorded signals using the model and a paired t-test is performed, which shows that the parameters are significantly different between the two groups. Further, a recursive cluster elimination based support vector machine is used to perform classification between the groups. An average classification accuracy of 99.46% is obtained, along with top classifiers. It is thus shown that the parameters of the Gaussian model show changes across groups and hence the model is effective in distinguishing the changes taking place due to the two different recording conditions. The study has potential applications in healthcare.

SInCRe-structural interactome computational resource for Mycobacterium tuberculosis

We have developed an integrated database for Mycobacterium tuberculosis H37Rv (Mtb) that collates information on protein sequences, domain assignments, functional annotation and 3D structural information along with protein-protein and protein-small molecule interactions. SInCRe (Structural Interactome Computational Resource) is developed out of CamBan (Cambridge and Bangalore) collaboration. The motivation for development of this database is to provide an integrated platform to allow easily access and interpretation of data and results obtained by all the groups in CamBan in the field of Mtb informatics. In-house algorithms and databases developed independently by various academic groups in CamBan are used to generate Mtb-specific datasets and are integrated in this database to provide a structural dimension to studies on tuberculosis. The SInCRe database readily provides information on identification of functional domains, genome-scale modelling of structures of Mtb proteins and characterization of the small-molecule binding sites within Mtb. The resource also provides structure-based function annotation, information on small-molecule binders including FDA (Food and Drug Administration)-approved drugs, protein-protein interactions (PPIs) and natural compounds that bind to pathogen proteins potentially and result in weakening or elimination of host-pathogen protein-protein interactions. Together they provide prerequisites for identification of off-target binding.

An Open-End winding IM drive with Multilevel 12-sided Polygonal Vectors with Symmetric Triangles

Multilevel inverters with hexagonal voltage space vector structures have improved performance of induction motor drives compared to that of the two level inverters. Further reduction in the torque ripple on the motor shaft is possible by using multilevel dodecagonal (12-sided polygon) voltage space vector structures. The advantages of dodecagonal voltage space vector based PWM techniques are the complete elimination of fifth and seventh harmonics in phase voltages for the full modulation range and the extension of linear modulation range. This paper proposes an inverter circuit topology capable of generating multilevel dodecagonal voltage space vectors with symmetric triangles, by cascading two asymmetric three level inverters with isolated H-Bridges. This is made possible by proper selection of DC link voltages and the selection of resultant switching states for the inverters. In this paper, a simple PWM timing calculation method is proposed. Experimental results have also been presented in this paper to validate the proposed concept.

Site-Selective Addition of Maleimide to Indole at the C-2 Position: Ru(II)-Catalyzed C-H Activation

Synthesis of 3-(indol-2-yl)succinimide derivatives is presented using a directing group strategy. Selective functionalization of C-2 in the presence of highly reactive C-3 in indole derivatives has been achieved. A conjugate addition product instead of Heck-type product has been brought about by careful selection of the alkene partner (maleimides and maleate esters) such that a beta-hydride elimination is avoided.