Modeling wind energy development barriers: implications for promoting green energy sector

Since a variety of barriers pose challenges to the Indian wind energy sector, the extent to which these barriers hamper this sector and the alternative solutions are largely unknown. We identify several barriers using existing literature, and then using the modified Delphi approach, refine 25 barriers and classify them into five significant dimensions. Later, the Analytical Hierarchical Process determined the ranking of barriers using pairwise comparison matrices. The Grey Technique for Order Preference by Similarity to Ideal Solution method ranked alternative solutions to these barriers. Results indicate that “financial barrier” is the most important barrier among all dimensions, while “limited government subsidy” is most influential among all sub-barriers. “Availability of adequate funds” is the best alternative to overcome these barriers. Finally, a sensitivity analysis is performed to validate the study findings. The study findings may assist practitioners and policymakers in boosting the current sluggish growth of the Indian wind sector.</p

In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To Treat Soft Tissue Sarcoma

The ability to activate drugs only at desired locations avoiding systemic immunosuppression and other dose limiting toxicities is highly desirable. Here we present a new approach, named local drug activation, that uses bioorthogonal chemistry to concentrate and activate systemic small molecules at a location of choice. This method is independent of endogenous cellular or environmental markers and only depends on the presence of a preimplanted biomaterial near a desired site (e.g., tumor). We demonstrate the clear therapeutic benefit with minimal side effects of this approach in mice over systemic therapy using a doxorubicin pro-drug against xenograft tumors of a type of soft tissue sarcoma (HT1080)

Additional file 1: Table S1. of BET protein inhibitor JQ1 inhibits growth and modulates WNT signaling in mesenchymal stem cells

Presenting a list of human primer sequences used in qRT-PCR. (DOCX 16 kb

DNA Helicases used in this study.

<p>DNA Helicases used in this study.</p

Sequestration of FANCJ, but not RECQ1, by cyclo dA.

<p><i>A,</i> Schematic of sequestration assay. Sequestration assays were performed with 9.6 nM FANCJ or 8.8 nM RECQ1 and the indicated concentrations of the competitor DNA forked duplex at 30°C (FANCJ) or 37°C (RECQ1) under sequestration assay conditions described in the Materials and Methods. <i>B</i> and <i>C,</i> FANCJ (<i>B</i>) or RECQ1 (<i>C</i>) unwinding of undamaged 19 bp tracker DNA substrate after incubation with unlabeled forked duplex DNA molecules that contained cyclo dA in the top, bottom, or neither strand. <i>D and E,</i> Quantification of FANCJ and RECQ1 helicase activity from representative sequestration experiments shown in panels <i>B</i> and <i>C</i>, respectively.</p

The accumulation of cyclopurine lesions in genomic DNA can cause replication errors or blockage leading to deleterious effects on the fidelity of DNA synthesis and maintenance of genomic stability which have negative outcomes for human health.

<p>The functions of certain DNA helicases can be adversely affected by cyclopurines and other forms of DNA damage which potentially impair helicase-dependent DNA damage response and repair pathways. See text for details.</p

Protein trap kinetics assay to measure FANCJ, DDX11, RECQ1, and EcUvrD rates of unwinding DNA substrates with cyclo dA.

<p>Reactions were performed under protein trap kinetic assay kinetics conditions described in the Materials and Methods. <i>A,</i> Schematic of protein trap kinetics helicase assay. <i>B</i>, Quantification of FANCJ helicase activity on cdA DNA substrates. <i>C</i>, Quantification of DDX11 helicase activity on cdA DNA substrates. <i>D,</i> Quantification of RECQ1 helicase activity on cdA DNA substrates. <i>E,</i> Quantification of EcUvrD helicase activity on cdA DNA substrates.</p

Effect of a site- and strand-specific cyclopurine lesion on FANCJ helicase activity.

<p>Helicase reactions were carried out by incubating the appropriate FANCJ concentrations with 0.5 nM forked duplex DNA that contained a cyclopurine lesion in the top strand (translocating-Cyclo T), bottom strand (nontranslocating-Cyclo B), or neither strand (Control) at 30°C for 15 min under standard helicase assay conditions described in the Materials and Methods. <i>E,</i> FANCJ unwinding of undamaged and cyclo dA damaged DNA substrates. Lane 1, no enzyme control; lanes 2–9 indicated concentrations of FANCJ; lane 10, heat- denatured DNA substrate control. <i>F,</i> Quantification of FANCJ helicase activity on cdA substrates with error bars. <i>G,</i> FANCJ unwinding of undamaged and cyclo dG damaged DNA substrates. lane 1, no enzyme control; lanes 2–9, indicated concentrations of FANCJ; lane 10, heat- denatured DNA substrate control. <i>H,</i> Quantification of FANCJ helicase activity on cdG substrates with error bars.</p

Effect of a site- and strand-specific cyclopurine lesion on WRN or EcRecQ helicase activity.

<p>Helicase reactions of 20 µl were carried out by incubating the appropriate WRN or EcRecQ concentrations with 0.5 nM forked duplex DNA that contained a cyclopurine lesion in the top strand (nontranslocating-Cyclo T), bottom strand (translocating-Cyclo B), or neither strand (Control) at 37°C for 15 min under standard helicase assay conditions described in the Materials and Methods. <i>A,</i> WRN unwinding of undamaged and cyclo dA damaged DNA substrates. lane 1, heat denatured DNA substrate control, lane 2 no enzyme control, lane 3–9, indicated concentrations of WRN. <i>B,</i> Quantification of WRN helicase activity on cdA substrates with error bars. <i>C,</i> EcRecQ unwinding of undamaged and cyclo dA damaged DNA substrates. Lane 1, no enzyme control; lanes 2–9, indicated concentrations of EcRecQ; lane 10, heat-denatured DNA substrate control. <i>D,</i> Quantification of EcRecQ helicase activity on cdA substrates with error bars.</p

Effect of a site- and strand-specific cyclopurine lesion on EcUvrD, EcDnaB or EcDinG helicase activity.

<p>Helicase reactions were carried out by incubating the appropriate EcUvrD, EcDnaB or EcDinG concentrations with 0.5 nM forked duplex DNA that contained a cyclopurine lesion in the top strand (nontranslocating-Cyclo T), bottom strand (translocating-Cyclo B), or neither strand (Control) at 37°C for 15 min under standard helicase assay conditions described in the Materials and Methods. <i>A,</i> EcUvrD unwinding of undamaged and cyclo dA damaged DNA substrates. Lane 1, no enzyme control; lanes 2–9, indicated concentrations of EcUvrD; lane 10, heat-denatured DNA substrate control. <i>B,</i> Quantification of EcUvrD helicase activity on cdA substrates with error bars. <i>C,</i> EcDnaB unwinding of undamaged and cyclo dA damaged DNA substrates. Lane 1, no enzyme control; lanes 2–9, indicated concentrations of EcDnaB; lane 10, heat-denatured DNA substrate control. <i>D,</i> Quantification of EcDnaB helicase activity on cdA substrates with error bars. <i>E,</i> EcDinG unwinding of undamaged and cyclo dA damaged DNA substrates. Lane 1, heat-denatured DNA substrate control; lane 2, no enzyme control; lanes 3–10, indicated concentrations of EcDinG. <i>F,</i> Quantification of EcDinG helicase activity on cdA substrates with error bars.</p