A Study on binding of hydroxamic acid derivative to DNA: experimental and computational approach

Small Gilligan molecules bind to DNA and artificially alter and/or inhibit the functioning of DNA. These small ligand molecules act as drug when alteration or inhibition of DNA function is required to cure or control a disease.The binding interaction of N-phenyllauroylhydroxamic acid with CTDNA was measured by four methods, (i) UV spectroscopic method, (ii) fluorescence spectroscopic method, (iii) viscosity Measurement and (iv) molecular docking. It showed that Nphenyllauroylhydroxamic acid-DNA complex has high absorption intensity than compound only and significant quenching of fluorescence intensity for the N-phenyllauroylhydroxamic-DNA complex. The values of binding constant, K, is 3.43x 10-2nd Stern Volmer constant Ksv is 4.8 x102 ng-1μl obtained by UV absorption and fluorescence spectral methods, respectively. The binding interaction is further confirmed by the increase in relative viscosity of CT-DNA. The molecular docking of N-phenyllauroylhydroxamic acid with the DNA confirmed to be a strong binder with DNA in the mode of groove

An improved algorithm for optimal load shedding in power systems

A blackout is usually the result of load increasing beyond the transmission capacity of the power system. A collapsing system enters a contingency state before the blackout. This contingency state is characterized by a decline in the bus voltage magnitudes. To avoid blackouts, power systems may start shedding load when a contingency state occurs called under voltage load shedding (UVLS). The success of a UVLS scheme in arresting the contingency state depends on shedding the optimum amount of load at the optimum time and location. This paper proposes a hybrid algorithm based on genetic algorithms (GA) and particle swarm optimization (PSO). The proposed algorithm can be used to find the optimal amount of load shed for systems under stress (overloaded) in smart grids. The proposed algorithm uses the fast voltage stability index (FVSI) to determine the weak buses in the system and then calculates the optimal amount of load shed to recover a collapsing system. The performance analysis shows that the proposed algorithm can improve the voltage profile by 0.022 per units with up to 75% less load shedding and a convergence time that is 53% faster than GA

River fragmentation and flow alteration metrics : a review of methods and directions for future research

Rivers continue to be harnessed to meet humanity’s growing demands for electricity, water, and flood control. While the socioecological impacts of river infrastructure projects (RIPs) have been well-documented, methodological approaches to quantify river fragmentation and flow alteration vary widely in spatiotemporal scope, required data, and interpretation. In this review, we first present a framework to visualise the effects of different kinds of RIPs on river fragmentation and flow alteration. We then review available methods to quantify connectivity and flow alteration, along with their data requirements, scale of application, advantages, and disadvantages. Finally, we present decision-making trees to help stakeholders select among these methods based on their objectives, resource availability, and the characteristics of the project(s) being evaluated. Thematic searches of peer-reviewed literature using topic-relevant keywords were conducted on Google Scholar. The bibliography of selected papers was also reviewed, resulting in the selection of 79 publications. Papers that did not define or apply a specific metric were excluded. With respect to fragmentation, we selected papers focused on instream connectivity and excluded those dealing with overland hydrologic connections. For flow alteration, we selected papers that quantified the extent of alteration and excluded those aimed at prescribing environmental flows. The expected hydrological consequences of various RIP types were ‘mapped’ on a conceptual fragmentation-flow alteration plot. We compiled 29 metrics of river fragmentation and 13 metrics to flow alteration, and used these to develop decision-making trees to facilitate method selection. Despite recent advances in metric development, further work is needed to better understand the relationships between and among metrics, assess their ecological significance and spatiotemporal scale of application, and develop more informative methods that can be effectively applied in data-scarce regions. These objectives are especially critical given the growing use of such metrics in basin-wide conservation and development planning

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis

Report on Computers in Practice: a survey of computers in architectural practice

This is a report on the dynamic relationship between information technology (IT) and architectural practice. The report summarises the attitudes and opinions of practitioners gathered through extensive recorded interviews, and compares these attitudes and opinions with the findings of other studies. The report is compiled from the point of view of an understanding of appropriating as preceding as the model for understanding. We thereby connect what is going on in IT with concepts currently under discussion in postmodern thought and in the tradition of philosophical pragmatism. We identify several of the major options identified by practitioners in their use of IT, including practicing without computers, substituting computers for traditional tasks, delivering traditional services in an innovative way through IT, and developing new services with IT. We also demonstrate how firms are changing and are being shaped by the market for architectural services. One of the major areas of change is in how IT and related resources are managed. We also consider how the role of the practitioner as an individual in a firm is changing along with changes in IT, and how different prognoses about the future of IT in practice are influenced by certain dominant metaphors. Our conclusion is that IT is best understood and appropriated when it is seen as fitting into a dynamic field or constellation of technologies and practices. Such an orientation enables the reflective practitioner to confront what is really going on as IT interacts with practice. praxis- practice theor

Interleukin-2 is Present in Human Blood Vessels and Released in Biologically Active Form by Heparanase

Interleukin-2 (IL-2) is a multifaceted cytokine with immunostimulatory and immunosuppressive properties. Our laboratory recently demonstrated that the availability of IL-2 is regulated, in part, by association with perlecan, a heparan sulfate proteoglycan. Given the abundance of perlecan in blood vessels, we asked whether IL-2 is present in vessel walls. Our results indicate that IL-2 is associated with endothelial and smooth muscle cells within the human arterial wall. This IL-2 is released by heparanase, and promotes the proliferation of an IL-2-dependent cell line. Given the presence of IL-2 in human arteries, we asked whether the large vessels of IL-2-deficient mice were normal. The aortas of IL-2-deficient mice exhibited a loss of smooth muscle cells, suggesting that IL-2 may contribute to their survival. In their entirety, these results suggest a here-to-fore unrecognized role of IL-2 in vascular biology, and have significant implications for both the immune and cardiovascular systems