Bioinformatics in Antifungal Design: Strategies To Overcome Resistance from a Proteomic Perspective

Economic theory recognizes the importance of investments in both technological innovation and political activity in firm behavior, and extensive research exists which examines independently these expenditures. However, surprisingly little attention is devoted to analyzing technological innovation and political action expenditures jointly. Technological innovation and political action are two of the options firms face regarding how to achieve lower costs or market power; the characteristics of these choices not only affect the degree to which each is used, but also have widely divergent normative and policy implications for society. Furthermore, many forms of technological innovation require regulatory approval, so that firms may use the two forms of investment in conjunction with each other in addition to treating them as separate investment alternatives. This paper investigates the relationships between firm investments in technological innovation and political activity. Both forms of investment seek to lower costs and/or create market advantage, but economists have long recognized the social importance of technological innovation to economic growth, while treating most firm political activity as inefficient. Growing social concerns surrounding declining innovation, productivity, and growth and increasing firm political activity suggest that these are timely dimensions to explore jointly. In the next section I discuss the relationship between firm investments in technological innovation and political action. This discussion motivates the subsequent empirical modelling presented in section III. Because of the possibility of simultaneity between firm spending in research and development (RD these results hold true to various degrees over industries and industry groups. Section VI offers conclusions and suggestions for further research.

This research paper explores the textile industry in Taiwan and investigates how technological innovation can support corporate competitiveness under the pressures of global market competition, increased labor costs, and sustainability. This study tests the impact of technological resources, competitive pressures, and innovation attitudes on corporate competitiveness, moderated by risk management capability and technological innovation investment. A stratified random sampling method and questionnaire survey produced 401 valid responses that were analyzed using structural equation modeling. The study found that technological resources, competitive pressure, and innovation attitudes positively affect risk management capability and technological innovation investment, which improve corporate competitiveness. Technological innovation investment had the most significant effect on corporate competitiveness of these three factors. This is because competitive pressure and innovative attitudes push firms towards increased research and development and investment that create differentiation in the market and sustainable advantages. In terms of theoretical contribution, this study addresses the research gap related to the interaction between risk management and innovation in traditional industries. The practical implication is that firms should consider investing in organizational processes that create innovative attitudes and allocate resources to maximize organizational capabilities and ensure a competitive advantage in highly dynamic markets through risk management and ongoing innovation.

The fungal keratitis (FK) infections that cause cornea inflammations are more virulent than other bacterial keratitis infections and remain one of the most ethereal and challenging infections for ophthalmologists to diagnose and treat. Thus, the urgency in understanding the current perspectives of antifungal agents and their interactions with novel therapeutic targets and the identification of novel anti-fungal agents are at the frontline of studies in the pharmaceutical industry. In this study, DNA dependent RNA polymerase was modelled and virtually screened against eight antifungal agents, and it was found that Itraconazole (−22.0427 kJ/mol), Ketoconazole (−20.2194 kJ/mol), and Voriconazole (−12.6388 kJ/mol) exhibited better binding interactions. further, the structural and electronic properties of Itraconazole calculated through density functional theory studies revealed the sites of chemical reactivity that are vital in the compounds for possible interactions with RNA polymerase (RNAP). Hence, this study explores the binding efficacies of various anti-fungal agents through docking studies and their chemical entities, which might pave a significant path for the design of novel anti-fungal agents against hyalohyphomycetes causing keratitis.

Innovation is a very important element of regional economic policy. It is of particular importance in the Arctic zone of the Russian Federation, where it can be one of the leading factors in its development, which is due to the importance of the AZRF as a whole. This article is devoted to assessing the relation-ship between investment in technological innovation by organizations and the development of the region’s economy. The following indicators were selected from statistical data and calculated for the implementation of the goal: the growth rate of investments in technological innovations, the growth rate of gross regional product and the labor productivity index for the regions of the AZRF. The present paper uses a regression-correlation analysis method by which correlation coefficients were calculated between the growth rate of investment in innovation and the growth rate of GRP, between the growth rate of investment in innovation and the productivity index, as well as the significance of their influence on the resulting signs. As a result, the main trends of investment processes in technological innovations in the AZRF from 2008 to 2018 were determined, the unique nature of the impact of investments in technological innovations on economic indicators in each individual region was established. It was also found out that the sectoral orientation of a particular territory does not unambiguously affect the correlation between the parameters under consideration. Based on the information obtained during the study, the author proposed a typology of the AZRF regions on the impact of investments in technological innovations on GRP and labor productivity, demonstrating the strength of both the relationship of these parameters in the region and the strength of the regional economy’s response to investment growth.

Government subsidies are an important means to guide enterprises’ investment in technological innovation. While countries are increasing government subsidies to enterprises, how to effectively leverage government subsidies is a concern of the academic community. At present, scholars’ research conclusions on the impact of government subsidies on enterprise technological innovation include promotion effect, extrusion effect, and mixing effect. Relevant research is often conducted from a single perspective. This paper studies the relationship between government subsidies and enterprise technological innovation, and integrates the macro-institutional environment, meso-market structure, and micro-corporate governance into the same framework. Taking information transmission, software, and information technology service companies as samples, it analyzes the influencing factors of the Chinese government research and development (R&D) subsidies on enterprises’ innovation investment. This paper uses Stata16 software to perform the least square analysis. The research shows that the Chinese government R&D subsidies have a significant incentive effect on corporate technology innovation investment. The higher the marketization process, the more dispersed its equity, and the government subsidy promotes corporate technology innovation investment. The more significant it is; for industries with different product market competition, government subsidies have no significant impact on enterprises’ investment in technological innovation. Based on empirical research conclusions, this study puts forward policy recommendations to increase the intensity of government subsidies and optimize the structure of corporate equity to increase the leverage effect of government subsidies.

Nowadays, the widespread diffusion of infections caused by opportunistic fungi represents a demanding threat for global health security. This phenomenon has also worsened by the emergence of contagious events in hospitalisation environments and by the fact that many fungi have developed harsh and serious resistance mechanisms to the traditional antimycotic drugs. Hence, the design of novel antifungal agents is a key factor to counteract mycotic infections and resistance. Within this context, nanomaterials are gaining increasing attention thanks to their biocidal character. Among these, carbon dots (CDs) represent a class of zero-dimensional, photoluminescent and quasi-spherical nanoparticles which, for their great and tuneable features, have found applications in catalysis, sensing and biomedicine. Nevertheless, only a few works define and recapitulate their antifungal properties. Therefore, we aim to give an overview about the recent advances in the synthesis of CDs active against infective fungi. We described the general features of CDs and fungal cells, by highlighting some of the most common antimycotic mechanisms. Then, we evaluated the effects of CDs, antimicrobial drugs-loaded CDs and CDs-incorporated packaging systems on different fungi and analysed the use of CDs as fluorescent nano-trackers for bioimaging, showing, to all effects, their promising application as antifungal agents.

Over the last 30 years or so, the incidence of invasive fungal infections in man has risen dramatically. Patients that become severely immunocompromised because of underlying diseases such as leukemia or recently, acquired immunodeficiency syndrome or patients who undergo cancer chemotherapy or organ transplantation, are particularly susceptible to opportunistic fungal infections. Although Candida species continue to be the major pathogenic fungi in these patients, cryptococcosis, aspergillosis, and coccidioidomycosis, among others, have become increasingly important mycoses. Antifungal drugs currently being used in clinic include polyene antibiotics, azole derivatives and 5-fluorocytosine. With the exception of the latter, all other drugs possess mechanisms of action aimed at disrupting the integrity of the fungal cell membrane by either interfering with the biosynthesis of membrane sterols or by inhibiting sterol functions. However, one significant obstacle preventing successful antifungal therapy is the dramatic increase in drug resistance, especially against azole antimycotics. Among the major mechanisms by which fungi invoke drug resistance is the overexpession of extrusion pumps able to facilitate the efflux of cytotoxic drugs from the cell thus leading to decreased drug accumulation and diminished concentrations. Since the initial observations that azole resistance by fungi may be caused by overexpression of multidrug efflux transporter genes, significant advances have been achieved primarily with Saccharomyces cerevisiae and Candida albicans. The purpose of this review is to discuss various aspects of multidrug resistance in fungi such as antifungal drug mechanisms of action and fungal molecular genetics in the context of targeted drug discovery. The role that membrane transporter proteins play in drug resistance in various species of Candida, Aspergillus and Cryptococcus will be address in more detail, as will be their importance as selective drug targets in the design of novel antifungal agents.

Management Problems of Investment in Technological Innovation, Using Artificial Neural Network

This article is focused on the space sector, mainly due to the devices developed and marketed that require high investments in research, development and technological innovation, supported by a permanent need to meet the standard requirement to guarantee their effectiveness, among all the correct certification. In such scenario, this article has examined, highlighting technological innovation, which are the context and elements involved in the certification of the Vehicle Survey Booster – 30 (VSB-30). The research is characterized as a case study, conducted in the first semester of 2011, and it consisted of reviewing the literature on technological innovation and certification as well as information available in various reports, some of which were public, and interviews. The article presents a brief description of the development of the VSB-30, its importance to the market and the relevant aspects of the certification and the Certification Body of Brazil. The conclusion is that the certification is a contribution to technological innovation for it provides benefits in process improvement, especially regarding the question of documentation, creating conditions for the industry to adapt to formal established and qualified processes and, in return, to become restricted to trade companies unable to adjust to these requirements.

Pharmacophore modeling and 3D QSAR studies of aryl amine derivatives as potential lumazine synthase inhibitors

3D-QSAR and molecular docking studies on benzothiazole derivatives as Candida albicans N-myristoyltransferase inhibitors

Crystallographic studies of homoserine dehydrogenase for the design of novel antifungal agents

Lanosterol 14alpha-demethylase (CYP51) is an essential enzyme in the fungal life cycle and also an important target for the antifungal drug development. Based on the multiple sequence alignments of CYP51 family, an evolutionary tree of the CYP51 family was constructed by the evolutionary trace (ET) method. The identified trace residues could provide a reliable and rational guide to the design of CYP51 mutations and give more information about the detailed mechanism of substrate (drug) recognition and binding. The reliability of ET analysis to identify residues of functional importance was validated by the reported site-directed mutagenesis studies of CYP51s. Several residues in the active site were also validated by our mutagenesis studies. Mapping the identified trace residues onto the active site of the modeled structure of Candida albicans CYP51 (CACYP51) may provide useful information for the design of novel antifungal agents.

Preparation of terpene-derived fungicidal candidates with a 1,3,4-thiadiazole moiety for natural product-inspired agrochemical discovery

Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors