ANTIMICROBIAL CHARACTERIZATION AND THERAPEUTIC APPLICATIONS OF NOVEL SYNTHETIC THIAZOLE COMPOUNDS AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCI AND ENTEROCOCCI

For more than a century, antibiotics have been valuable allies in combating an array of bacterial infections. However, each year nearly 23,000 people in the United States of America and 25,000 people in Europe die due to infections that are recalcitrant to currently available antimicrobials. The emergence of drug-resistant bacterial species, namely methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has limited the efficacy of several classes of antibiotics. Compounding this problem further is that many large pharmaceutical companies have left the field of antibacterial drug discovery given the high cost of innovation and low return on investment. Collectively, this highlights an urgent, unmet need to identify and develop new antibacterial agents that attack unique molecular targets in bacterial pathogens. Here, we investigate the antibacterial activity of a new series of phenylthiazole antibiotics against a panel of clinically-relevant ‘ESKAPE’ pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The lead compound 1 was identified through whole-cell screening of libraries of substituted thiazoles and thiadiazoles. Subsequent derivatives were constructed in an attempt to enhance potency, decrease toxicity to host tissues, and improve the lead compound’s drug-like properties. Broth microdilution assay results show that the lead 1 and two derivatives (2 and 3) possess potent activity against Gram-positive bacterial pathogens including MRSA, methicillin-resistant Staphylococcus pseudintermedius (an emerging pathogen of importance in veterinary medicine) and VRE, inhibiting the growth of clinical isolates at concentrations as low as 0.5 µg/mL. The presence of the outer membrane and efflux pumps appears to impede the antibacterial activity of the phenylthiazoles against Gram-negative bacteria. MRSA and VRE mutants resistant to the phenylthiazoles could not be isolated, both via single-step and multi-step resistance selection analysis. The compounds exerted a rapid bactericidal effect, targeting cell wall synthesis as deduced from Bacterial Cytological Profiling. Transposon mutagenesis suggested three possible targets: YubA, YubB and YubD. YubB is undecaprenyl diphosphate phosphatase (UPPP) and UPPP as well as undecaprenyl diphosphate synthase (UPPS) were inhibited by 1, as confirmed by traditional enzyme inhibition assays. YubA and YubD are annotated as transporters and may also be targets since 1 collapsed the proton motive force in membrane vesicles. This indicates the phenylthiazole antibacterial agents have a unique mechanism of action that involves inhibition of key enzymes involved in peptidoglycan biosynthesis and potential transporters. This may contribute to the inability to generate bacterial mutants exhibiting resistance to the phenylthiazoles. The compounds were not toxic up to 20-40 µg/mL against different human cell lines including keratinocytes (HaCaT), kidney cells (HEK293), and colorectal cells (HRT-18). Additionally, the compounds were found to be non-toxic (at 20 µg/mL) in a Caenorhabditis elegans animal model. Closer inspection of the physicochemical profile and in silico pharmacokinetic profile of the lead 1 and more metabolically-stable analogue 3 revealed potential application for use topically (for localized skin infections), intravenously (for systemic infections), and as decolonizing agents. Utilizing a murine skin infection model, 1 and 3 were found to significantly reduce the burden of MRSA in infected lesions by more than 96%. Furthermore, both compounds (at 20 µg/mL) were potent in vivo, reducing the burden of VRE in infected C. elegans. Taken altogether, the results indicate that phenylthiazoles 1 and 3 are promising novel topical antibacterial agents and decolonizing agents for use in the treatment of drug-resistant staphylococcal and enterococcal infections

A Review of Information Security from Consumer’s Perspective Especially in Online Transactions

In the current internet technology, most of the transactions to banking system are effective through online transaction. Predominantly all these e-transactions are done through e-commerce web sites with the help of credit/debit cards, net banking and lot of other payable apps. So, every online transaction is prone to vulnerable attacks by the fraudulent websites and intruders in the network. As there are many security measures incorporated against security vulnerabilities, network thieves are smart enough to retrieve the passwords and break other security mechanisms. At present situation of digital world, we need to design a secured online transaction system for banking using multilevel encryption of blowfish and AES algorithms incorporated with dual OTP technique. The performance of the proposed methodology is analyzed with respect to number of bytes encrypted per unit time and we conclude that the multilevel encryption provides better security system with faster encryption standards than the ones that are currently in use

Reasons for Afghan Teachers’ First Language Use in EFL Classes

The use of L1 in EFL classes has been an ongoing debate for many years since language educators use L1 in EFL classes for different reasons. Therefore, this study aims to investigate the reasons for Afghan teachers' L1 use in EFL classes at Balkh University. Semi-structured interview was conducted with a sample of 5 EFL educators with 10-15 years of teaching experience from the English Department of Balkh University. The sample for the study was chosen purposively due to proximity, easy accessibility and availability of the participants. Content analysis was employed for the analysis of the obtained data from the study based on the emergent themes. The result shows that Afghan EFL teachers at Balkh University use L1 in their classes for different purposes, namely, as a pedagogical tool for clarification, as a tool for establishing rapport, as a discipline and class management tool, based on curriculum and syllabus demand and as per need of students’ level of language proficiency

The Public Libraries Perspective in Pakistan: A Study on Empirical Problems

Purpose: This study examined the problems faced by the public of Pakistan. It also analyzed the demographic information of the libraries and further reviewed the designation, qualifications, and professional experience of the heads/in-charge of public libraries. Research Methodology: The census-based survey was conducted, and data was collected from the 119 public libraries through the structured questionnaire. The collected data was analyzed using Statistical Package for Social Sciences (version-23) and both descriptive and inferential stats were applied to analyze the data and interpret the results. Key Findings: The heads of 91 libraries were LIS professionals, while 28 libraries were run by non-professional staff. The major problems identified were lack of training opportunities, limited human resources, insufficient IT & LIS professional staff, limited electronic resources, interrupted power supply, limited information resources, lack of commitment from the upper management and lack of financial resources. It was also observed that public libraries in Balochistan faced more problems than libraries of other provinces. Practical Implications: The findings of the study are useful for policymakers and managers of public libraries. Major points to be considered include a) more posts of professional staff should be created and appointed; b) the existing libraries need to be upgraded, and new and well-equipped public libraries should be established at district and tehsil levels to meet the people\u27s information and recreation needs

Research in the Field of Prefabricated Building Management: A Case Study

Due to its low energy consumption, short construction period, low labor cost, and great construction efficiency, prefabricated buildings have garnered extensive interest from scholars worldwide as a novel production method. Nevertheless, research on prefabricated houses is not yet thoroughly analyzed. This study summarized the existing state and research hotspots of prefabricated building research by thorough study and summarization of research on prefabricated buildings. According to the findings, there are five key areas of study within the prefabrication field: the sustainability of prefab structures, their meaning and current state of development, the development environment, project lifecycle management, and organizational management. Finally, offer some recommendations for future theoretical and practical work on prefabricated structures based on where the industry is at the moment in terms of development.&nbsp

The Effect of Computer Crimes on the Application of Information System in Banks in Jordanian Firms

This study aims to identify the effect of computer crimes on the application of information system in bank sector in Jordan. The study relied on both data resources; the primary and the secondary data were collected from a previous studies related to the subject matter, where as the primary data attained through distributing the questionnaire on the study sample. The researchers conducted a statistical analysis for approximately 300 questionnaires  , which were distributed on a sample of Jordan commercial banks, then the responses of the study sample were emptied into the computer, the data analysis was conducted by using statistical analysis system(SPSS), the result showed: There is a relation that has a moral effect between the dangers of viruses and efficiency of the information systems. There is a relation that has a moral effect between the dangers of penetration/violation and the efficiency of information systems. There is a relation that has a moral effect between losing and smuggling of information and the efficiency of information systems. In light of the previous results, the researchers suggest a group of recommendations: The researchers recommend the increase of research related to computer crimes, since it is clear from this study that there is a big gap in studies related to this approach. To publish statistics linked to the internet crimes and its misuse by concerned parties to identify the size of the problem. To form specialized committees of experienced figures to set special laws regarding the computer and the internet crimes in a detailed fashion of laws and regulations in an efficient way in Jordanian judicial authorities. Keywords: Computer Crimes, Viruses, Penetration/Violation, Administrative Information System

The impact of foreign aid on national development : a case study of Bangladesh

v, 171 leaves ; 28 cm.Includes abstract.Includes bibliographical references (leaves 157-171).This study is concerned with the impact of foreign aid on development in third world countries. It focuses particularly on the negative impact of aid on recipient countries in a case study of Bangladesh. The Structural Adjustment Programme (SAP) is a part of aid conditionalities and here in this study I trace out the socio-economic impact of the SAP. I review two schools of thought; one that is supportive of aid arguing that aid is a catalyst or driving force for development, and another decidedly critical school that argues that foreign aid is not a catalyst for development but rather as a catalyst for accumulating resources from developing countries and creating a market for the developed world. In this connection I review considerable evidence that suggest that foreign aid is dictated by political and strategic considerations much more than by the economic needs and policy performance of the recipients. The thesis of this study is that foreign aid, rather than being a means to economic and social development, has largely become a means by which most of the developing countries are being exploited. Bangladesh since its independence in 1971 provides backdrop for the research and analysis involved in this thesis

Restaurant Hope: Engineering a Choice-Based Service Initiative to Address Hunger

The objective of this service-learning project was to humanize the face of hunger for volunteers by empowering patrons attending a soup kitchen with the choice of selecting their meal for dinner. This experience helped foster an emotional connection between patrons and volunteers. A traditional soup kitchen utilizes a single-option, inexpensive meal approach that is cooked and delivered by volunteers. However, this service project, entitled Restaurant Hope, addressed these issues by providing patrons with a diverse menu. In addition, patrons were given the opportunity to request more food (to try other options on the menu) and take home leftover food depending on availability. Choices patrons made in terms of menu preferences were tracked. Volunteers, soup kitchen administrators, and patrons were interviewed to obtain feedback on this service initiative and how it impacted their perceptions on the issue of hunger in their local community

Mapping Fuzzy Petri Net to Fuzzy Extended Markup Language

Use of model gives the knowledge and information about the phenomenon also eradicates the cost, the effort and the hazard of using the real phenomenon. Characteristics and concepts of Petri nets are in a way that makes it simple and strong to describe and study the information processing system; especially it is shown in those which are dealing with discrete, concurrent, distributed, parallel and indecisive events. Yet, due to Petri nets inability to face with systems working on obscure data and continues events, the interest to develop fundamental concept of Petri nets has been raised which is led to new style of presented model named "fuzzy Petri nets". The difference in Petri nets is in the elements that have been fuzzed. Transitions, places, signs and arcs can be fuzzed. PMNL, on the other hand as a markup language has been engaged in uttering Petri nets in previous researches. Fuzzy markup nets can model the uncertainty of concurrent scenarios different from a dynamic system by a board of parameters and use of fuzzy membership dependencies. Therefore, in order to define these uncertain data, it is vital to use a formal language to describe fuzzy Petri nets. To support this version in this thesis, a markup language will be presented stating the structure and grammar of markup language and covering fuzzy concepts in Petri nets as well. Presenting the suggested grammar accommodates the support of fuzzy develope.DOI:http://dx.doi.org/10.11591/ijece.v3i5.403