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The primary aim of this study was to incorporate biologically active pharmacophores like 1,3,4-thiadiazole and Schiff base moiety into metronidazole without modifying the nitro group. The synergy arising from the successful incorporation of imidazole ring, thiadiazole ring and Schiff's base pharmacophore was exploited in this research. It was expected that, since these pharmacophores have individual antibacterial and anthelmintic activity, their successful incorporation in one molecule would improve the antibacterial and anthelmintic activity of the compound along with improved safety and efficacy. Some compounds (1, 1b, 1f and 1e) showed significant antibacterial activity compared to the standard. Similarly, compounds 1, 1b and 1g exhibited significant anthelmintic activity against P. excavatus and P. species. [ABSTRACT FROM AUTHOR]

A multilevel inverter plays a predominant role in improving the performance as well as efficiency of the inverter. In this study, the proposed idea of the selective harmonic elimination (SHE) for Duple Voltage Boosting nine-level inverter topology with fewer switching components possesses two times better voltage boosting capability than the considered conventional models. The proposed inverter comprises 12 power semiconductor switches, two capacitors, and a single diode, which is connected to a single dc (direct current) source. The duple 9-level topology has been studied and evaluated under different multicarrier PWM (pulse width modulation) techniques in order to obtain lw THD (total harmonic distortion), and the results proves that the Level Control PWM Technique exhibits a better THD value of 9.35%. To improve the quality of the output waveform, the SHE has been designed to fix the predominant harmonics so that the lower order harmonics are minimized to generate a lower THD. A detailed discussion has been made with the results of the proposed inverter THD, which are then compared with other nine-level inverters MATLAB/SIMULINK that has been used to perform the simulation of the duple model, and the obtained simulation results have been validated for different modulation indices. The FPGA SPARTAN 6E controller tests the experimental prototype of the nine-level inverter, and their cost function is represented in dollars, which is compared with the other similar nine-level inverters. [ABSTRACT FROM AUTHOR]

The present investigation was conducted to examine antimicrobial activity of rhizome extracts of Curcuma caesia, Curcuma amada and Curcuma angustifolia. The antibacterial activity of the methanol extract of Curcuma caesia, Curcuma amada and choloroform extract of Curcuma angustifolia was tested against Escherichia coli and Bacillus subtilis bacterial strains. Ofloxacin and ciprofloxacin were taken as a standard reference for antibacterial activities. The methanol extracts of Curcuma caesia showed the highest antibacterial activity than methanol extract of Curcuma amada and chloroform extract of Curcuma angustifolia. Dose-dependent inhibition was observed in all the studies. [ABSTRACT FROM AUTHOR]

Abstract: The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O6meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6. [Copyright &y& Elsevier]

ABSTRACT: DNA mismatch repair (MMR) maintains genomic integrity by correction of mispaired bases and insertion–deletion loops. The MMR pathway can also trigger a DNA damage response upon binding of MutSα to specific DNA lesions such as O6methylguanine (O6meG). Limited information is available regarding cellular regulation of these two different pathways. Within this report, we demonstrate that phosphorylated hMSH6 increases in concentration in the presence of a G:T mismatch, as compared to an O6meG:T lesion. TPA, a kinase activator, enhances the phosphorylation of hMSH6 and binding of hMutSα to a G:T mismatch, though not to O6meG:T. UCN-01, a kinase inhibitor, decreases both phosphorylation of hMSH6 and binding of hMutSα to G:T and O6meG:T. HeLa MR cells, pretreated with UCN-01 and exposed to MNNG, undergo activation of Cdk1 and mitosis despite phosphorylation of Chk1 and inactivating phosphorylation of Cdc25c. These results indicate that UCN-01 may inhibit an alternative cell cycle arrest pathway associated with the MMR pathway that does not involve Cdc25c. In addition, recombinant hMutSα containing hMSH6 mutated at an N-terminal cluster of four phosphoserines exhibits decreased phosphorylation and decreased binding of hMutSα to G:T and O6meG:T. Taken together, these results suggest a model in which the amount of phosphorylated hMSH6 bound to DNA is dependent on the presence of either a DNA mismatch or DNA alkylation damage. We hypothesize that both phosphorylation of hMSH6 and total concentration of bound hMutSα are involved in cellular signaling of either DNA mismatch repair or MMR-dependent damage recognition activities. [ABSTRACT FROM AUTHOR]

Abstract: DNA mismatch repair (MMR) within human cells is hypothesized to occur primarily at the replication fork. However, experimental models measuring MMR activity at specific phases of the cell cycle and during genomic DNA synthesis are lacking. We have investigated MMR activity within the nuclear environment of HeLa cells after enriching for G1, S and G2/M phase of the cell cycle by centrifugal elutriation. This approach preserves physiologically normal MMR activity in cell populations subdivided into different phases of the cell cycle. Here we have shown that nuclear protein concentration of hMutSα and hMutLα increases as cells progress into S phase during routine cell culture. MMR activity, as measured by both in vitro and in vivo approaches, increases during S phase to the highest extent within normally growing cells. Both fidelity and activity of MMR are highest on actively replicating templates within intact cells during S phase. The MMR pathway however, is also active at lower levels at other phases of the cell cycle, and on nonreplicating templates. [Copyright &y& Elsevier]

Renewable energy (RE) resources have reached the top-notch state in satisfying the energy demands of recent days. Solar photovoltaic (PV) is considered as a clean form of energy among the various RE resources. A novel single-phase grid-integrated solar PV system with Re-lift Luo converter with aid of a chicken swarm (CS) optimization algorithm is presented. The Re-lift Luo converter is implemented as it has maximum power density, extreme efficacy, high-voltage-gain ratio, and reduced switching losses. Since the PV output is intermittent, the output of the converter also gets varied, which will be maintained constant by implementing a proportional–integral (PI)-based closed loop control through the optimized CS algorithm. The normalized output is further applied to the grid via single-phase voltage source inverter. A battery is utilized to store the daytime's solar energy and discharges to the grid during the night time. The monitoring of the battery's state of charge (SoC) is performed by recurrent neural network (RNN). A PI controller achieves the real and reactive grid side power control. The novelty of the proposed work is the utilization of three control strategies such as PI, CS, and RNN in improving the overall performance of a grid connected system in improving the power quality. Proper control and analysis of the converters and battery through intelligent controllers are the major objectives of the paper. The outcome of the proposed concept reigns in the improvement of power quality and the proper estimation of SoC, which was supported by the detailed simulation and experimental studies. The proposed configuration is verified by simulation in MATLAB/Simulink and also tested in a real-time experimental setup, and the obtained results are as per the IEEE standards. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a research, which suggests the central nervous system (CNS) as the target of graft-versus-host-disease (GVHD) in rhesus macaque and the mediation by integrin-expressing CD8+ T cells to CNS GVHD.

This paper proposes a new reconfigure technique to improve efficiency by reconfiguring the photovoltaic array during the different partial shading conditions and comparative analysis with various partial shading mitigating techniques. Normally, the photovoltaic array efficiency is less even if the shading occurs in parts on the PV panels in an array. To extract maximum output from solar PV panels, the different modulation and MPPT techniques are utilized. Due to continuous and discontinuous partial shading, this MPPT technique also fails to perform a uniform power voltage curve. Therefore, to improve the efficiency and performance of the PV array, a prudent solution is needed to dispersing the shading by reconfiguring the solar panel array. Most of the present reconfiguration schemes are quite complex, succumb to erroneous execution, and not suitable for practical implementations. The proposed Intelligent Reconfiguration Technique (IRT) technique is well suited for extension of power ranges and it offers smooth power vs voltage graph there by the algorithm struck up in local maxima can be averted. Also the superiority of the IRT method quantitatively proven in Table 6 by comparing other methods with various shading patterns. [ABSTRACT FROM AUTHOR]

Untreated HIV-positive (HIV-1+) individuals frequently suffer from HIV-associated neurocognitive disorders (HAND), with about 30% of AIDS patients suffering severe HIV-associated dementias (HADs). Antiretroviral therapy has greatly reduced the incidence of HAND and HAD. However, there is a continuing problem of milder neurocognitive impairments in treated HIV+ patients that may be increasing with long-term therapy. In the present study, we investigated whether envelope (env) genes could be amplified from proviral DNA or RNA derived from brain tissue of 12 individuals with normal neurology or minor neurological conditions (N/MC individuals). The tropism and characteristics of the brain-derived Envs were then investigated and compared to those of Envs derived from immune tissue. We showed that (i) macrophage-tropic R5 Envs could be detected in the brain tissue of 4/12 N/MC individuals, (ii) macrophage-tropic Envs in brain tissue formed compartmentalized clusters distinct from non-macrophage-tropic (non-mac-tropic) Envs recovered from the spleen or brain, (iii) the evidence was consistent with active viral expression by macrophage-tropic variants in the brain tissue of some individuals, and (iv) Envs from immune tissue of the N/MC individuals were nearly all tightly non-mac-tropic, contrasting with previous data for neuro-AIDS patients where immune tissue Envs mediated a range of macrophage infectivities, from background levels to modest infection, with a small number of Envs from some patients mediating high macrophage infection levels. In summary, the data presented here show that compartmentalized and active macrophage-tropic HIV-1 variants are present in the brain tissue of individuals before neurological disease becomes overt or serious. IMPORTANCE The detection of highly compartmentalized macrophage-tropic R5 Envs in the brain tissue of HIV patients without serious neurological disease is consistent with their emergence from a viral population already established there, perhaps from early disease. The detection of active macrophage-tropic virus expression, and probably replication, indicates that antiretroviral drugs with optimal penetration through the blood-brain barrier should be considered even for patients without neurological disease (neuro-disease). Finally, our data are consistent with the brain forming a sanctuary site for latent virus and low-level viral replication in the absence of neuro-disease. [ABSTRACT FROM AUTHOR]