New Diazo Reagents and Applications of β-Lactones for Synthesis and Biological Evaluation of Natural Products

Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic agents. We have developed a set of second generation diazo reagents with small steric footprints, namely an alpha-trifluoroethyl (HTFB) diazo reagent, for simultaneous arming and SAR studies of bioactive natural products. The Rh(II)-catalyzed O-H insertions of several alcohol-containing natural products, including the potent translation inhibitor lactimidomycin, are investigated and useful reactivity and both chemo- and site- (chemosite) selectivities are observed. The alpha-trifluoroethyl diazo reagents (HTFB) shows clear differences in the IL-2 reporter assay with FK506 derivatives and provides greater retention of biological activity in a hMetAP2 proliferation assay of fumagillol derivatives compared to the first generation pbromophenyl diazo reagent (HBPA). The synthetic utilities of the new alpha-trifluoroethyl diazo reagent (HTFB) provide a great new tool for basic cellular studies facilitating the discovery of new drug candidates for human disease. Furthermore, we are interested in methodologies for beta-lactone synthesis and transformations. In this study, we demonstrated synthetic versatilities of beta-lactones for the synthesis of beta-lactam congeners of orlistat as fatty acid synthase inhibitors via SnCl4- promoted tandem Mukaiyama aldol-lactonization (TMAL) reaction and a one-pot, mild conversion of beta-lactones to beta-lactams. The inhibitory activities of the derived beta-lactam derivatives are determined in a biochemical fluorogenic assay using recombinant FASTE, and the micro-molar range FAS-TE inhibitory activities were observed. Additionally, we pursued synthetic studies toward the total synthesis of spongiolactone, which is a unique beta-lactone-containing marine diterpenoid, isolated from the marine sponge Spongionella gracilis. This natural product bears a unique tricyclic beta-lactone core possessing four contiguous stereogenic centers and an additional stereogenic quaternary carbon on a cyclohexyl appendage. We completed the total synthesis of 6,15-bis-epi-spongiolactone by employing an intramolecular nucleophilecatalyzed aldol-lactonization (NCAL) process as the key step to construct the fused tricyclic beta-lactone core. Importantly, we developed a double diastereoselective and, for the first time, a kinetic resolution via the NCAL process that enables an enantioselective strategy to the tricyclic beta-lactone core of (+)-spongiolactone

วิเคราะห์ผลกระทบของเตาหลอมอาร์คไฟฟ้าต่อคุณภาพไฟฟ้าของระบบ และเพิ่มประสิทธิภาพการใช้พลังงานเพื่อลดความร้อนสูญเสียของเตา ในสภาวะสมดุลพลังงานของกระบวนการผลิตเหล็ก

บทคัดย่อบทความวิจัยนี้นำเสนอการวิจัยของเตาหลอมอาร์คไฟฟ้าจำแนกเป็น 2 ส่วนคือ ส่วนที่ 1 ทำการวิเคราะห์ถึงผลกระทบการทำงานของเตาหลอมอาร์คไฟฟ้าที่เป็นแหล่งกำเนิดฮาร์มอนิก เพราะว่ามีสาเหตุมาจากการรบกวนในระบบที่มีคุณลักษณะความไม่เป็นเชิงเส้นในการอาร์คจะเกิดขึ้นเนื่องจากเตาหลอมอาร์คไฟฟ้า ทำการวัดสัญญาณแรงดันกระเพื่อมด้วยการจำลองแบบ Novel Arc Furnace โดยใช้โปรแกรมสำเร็จรูป PSCAD/ EMTDC ช่วยในการวิเคราะห์ เพื่อใช้เป็นแนวทางศึกษาการทำงานของเตาหลอมนี้ และวิธีแก้ไขปัญหาที่เกิดขึ้นโดยการติดตั้ง Static Var Compensateที่ระบบไฟฟ้าของโรงงานอุตสาหกรรมผลิตเหล็ก ผลการวัดสัญญาณแรงดันกระเพื่อมพบว่าทำให้เกิดสัญญาณแรงดันเปลี่ยนแปลงไปในช่วงที่แคบลงและมีสัญญาณลดน้อยลงในระบบ และส่วนที่ 2 นำเสนอถึงการเพิ่มประสิทธิภาพการใช้พลังงานโดยการทดลองการหลอมเหล็ก เพื่อหาปริมาณความร้อนสูญเสียผ่านผนังเตา ปริมาณการสูญเสียความร้อนจากการเผาไหม้ ปริมาณการสูญเสียความร้อนออกจากเตาทั้งหมด  เป็นต้น ทำให้ลดความร้อนสูญเสียในสภาวะสมดุลพลังงานของกระบวนการผลิตเหล็ก โดยควบคุมอุณหภูมิน้ำเหล็กที่เทจากเตาหลอมไปสู่เบ้ารับน้ำเหล็กเพื่อลดการสูญเสียความร้อนให้ต่ำลงประมาณ 2.89 กิโลวัตต์ ผลการวิเคราะห์และการทดลองในการปรับปรุงพบว่าการใช้พลังงานของเตาหลอมอาร์คไฟฟ้านี้ ทำให้สามารถเพิ่มประสิทธิภาพการใช้พลังงานได้ประมาณ 99.56 %AbstractThis paper presents the research of an electric arc furnace classified into 2 part. The first is analysis of    the impact of the electric arc furnace which is a harmonic source. It is caused by a disturbance in a system with non-linear characteristics of the arcs is caused due to an electric arc furnace. Ripple voltage measurement relies on replication of Novel Arc Furnace model by using PSCAD/EMTDC help in the analysis, which is used as a guide to study the function of this furnace and how to fix the problem by installing the Static Var Compensate the system of industrial steel production. Measurement results signal that causes the ripple voltage signal changes in a small range, and the signal is reduced in the system. The second, presented to enhance energy efficiency by experimental melting steel to find the amount of heat loss through the wall furnace.  Loss of heat from burning. Loss of heat from the stove to heat all the losses in energy homeostasis, a smelting process is controlled by the temperature of the steel which is poured from the furnace to the crucible and steel to reduce heat loss is reduced by approximately 2.89 kW, the resulting analysis and experiments to improve the energy of electric arc furnaces, this paper can increase energy efficiency by approximately 99.56 %

Electromagnetic Field Analysis on Surge Response of 500 kV EHV Single Circuit Transmission Tower in Lightning Protection System using Neural Networks

Abstract : This paper presents a technique for electromagnetic field analysis on surge response due to Mid-span back-flashovers effects in lightning protection system of 500 kV EHV single circuit transmission tower by the neural networks method. These analyses are based on modeling lightning return stroke as well as on coupling the electromagnetic fields of the stroke channel to the line. The ground conductivity influences both the electric field as well as the coupling mechanism and hence the magnitude and wave shape of the induced voltage. The technique can be used to analyzed the corona voltage effect, the effective of stroke to the span tower, the surge impedance of transmission lines. The maximum voltage from flashovers effects in the lines. The model is compatible with general electromagnetic transients programs such as the ATP-EMTP. The simulation results show that this study analyses for time-domain with those produced by a cascade multi-section model, the surge impedance of a full-sized tower hit directly by a lightning stroke is discussed

A simple and rapid colorimetric detection of methanol, ethanol, and isopropanol and its application toward alcohol-based hand sanitizer quality control

ABSTRACTA practical colorimetric analysis for alcohol determination was devised using a composite of food colorants, specifically a green solution of brilliant blue FCF and tartrazine at a ratio of 1:5 v/v. This colorimetric method was characterized by its simplicity, user-friendliness, environmental compatibility, cost-effectiveness, and suitability for self-measurement through visual examination. The colorimetric procedure entails admixture 1 mL of the alcohol sample with 50 µL of the green test solution and 250 µL of a 30% NaOH solution at ambient temperature. The ensuing color changes were visually assessed within 5 min. Through color sensing, methanol, ethanol, and isopropanol were identified by the manifestation of lemon yellow, orange, and biphasic solutions, respectively. Ethanol was semi-quantified based on color sensing from green to orange, with corresponding concentration ranges. The limit of detection for both methanol and ethanol was determined to be 30% v/v. The developed method demonstrated an accuracy of 93%, with the error range of 1 − 10% v/v and standard deviation of 3.9% v/v, as confirmed by the analysis of 100 commercially available alcohol-based hand sanitizers. This methodology has the potential for further expansion to encompass a wide range of rapid colorimetric analyses of products containing alcohol, including food items, alcohol raw materials, and cosmetics

Chemistry of Renieramycins. Part 19: Semi-Syntheses of 22-O-Amino Ester and Hydroquinone 5-O-Amino Ester Derivatives of Renieramycin M and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cell Lines

Two new series of synthetic renieramycins including 22-O-amino ester and hydroquinone 5-O-amino ester derivatives of renieramycin M were semi-synthesized and evaluated for their cytotoxicity against the metastatic non-small-cell lung cancer H292 and H460 cell lines. Interestingly, the series of 22-O-amino ester derivatives displayed a potent cytotoxic activity greater than the hydroquinone derivatives. The most cytotoxic derivative of the series was the 22-O-(N-Boc-l-glycine) ester of renieramycin M (5a: IC50 3.56 nM), which showed 7-fold higher potency than renieramycin M (IC50 24.56 nM) and 61-fold more than jorunnamycin A (IC50 217.43 nM) against H292 cells. In addition, 5a exhibited a significantly higher cytotoxic activity than doxorubicin (ca. 100 times). The new semi-synthetic renieramycin derivatives will be further studied and developed as potential cytotoxic agents for non-small-cell lung cancer treatment

Designing of a Framework for Applying Business Intelligence to Improve the Relationship between Academia and Industry

AbstractThe aim of the current research is to identify the dimensions (layers) of a framework for applying business intelligence to improve the relationship between academia and industry. According to its purpose, the research method is applicable; and in terms of implementation, it is qualitative, descriptive and thematic analysis. Fuzzy Delphi method was used to collect information. The statistical population of this research included 12 professors and specialists in the field of communication with industry, selected by the available method, and interviews were conducted with them. According to the analysis that was carried out using thematic analysis method to identify the layers of applying business intelligence to improve the relationship between university and industry, 7 dimensions and 57 indicators were identified and confirmed. Data analysis was done using MAXQDA 2018 software. The results showed that the dimensions of using business intelligence to improve the relationship between university and industry include the first layer/preparation of the environment, the second layer/data collection, the third layer/ETL (extraction, transfer, loading of data), the fourth layer/warehousing Data, and the fifth layer/user interface (UI), metadata management and change management.Extended AbstractIntroductionFor business intelligence to be useful in a company, it should be promoted from top management and the necessary resources should be provided and decisions should be made based on information. Business intelligence monitoring addresses various issues including investment, project prioritization, project management, and data quality. If monitored, business intelligence can be a powerful driver of business strategy. In fact, business intelligence can have a direct impact on the financial aspects of the organization. The best actions taken in business intelligence can be presented based on laws and regulations as well as suggestions to control the value of business intelligence actions, and this factor leads to more income than capitalization. The Business Intelligence Competence Center is a group of information technology business and analysts who work together to provide business intelligence solutions and organizational needs in the organization (Hoseinloo et al, 2021).The success of countries in the future will depend on the extent and manner of their growth and influence in their scientific, research and strategic products. With continuous progress in science, technology and culture, countries have been able to continuously improve the level of standards, to the extent that they have brought vast global markets under control of themselves and their new knowledge and technologies in the national and transnational arenas. Applying knowledge and excelling in technology is one of the main indicators of the development of societies (Hamed et al, 2022).Therefore, the researcher asked the main question: what are the dimensions (layers) of the framework for applying business intelligence to improve the relationship between academia and industry?Theoretical frameworkMany organizations today have adopted business intelligence as a catalyst to meet specific business needs and improve effectiveness. Business intelligence is about how to capture, access, understand, analyze and change one of the most valuable assets of a company to actionable information to improve business performance (Hoseinloo et al, 2021). Business intelligence systems have a great impact on the quality of strategic decisions in order to reduce decision time.BIS promotes the management quality in organization through new type of technology and techniques of extraction, change, process, and offer data in order to provide strategic information. Therefore, it must be ensured that the organization follows a good BI architecture plan in its implementation process so that BI success is achieved. Business intelligence architecture is a framework consisting of various BI components (for example, data, people, processes, technology and management) and how these components should come together to ensure the smooth operation of a BI system (Ankrah & Tabbaa, 2015).Zhang et al, (2022) in a research entitled "The effects of the depth and breadth of university-industry alliance portfolio on the growth of new technology-based firms": states evidences from China that in emerging economies, new technology-based firms (NTBF) are often at the same time, make multiple alliances with universities and research institutes to access knowledge and external resources critical to their survival and growth, thus forming University-Industry Alliance Portfolios (UIAP). However, little attention has been paid to this phenomenon. The results show the negative effects of UIAP depth on company growth and the positive effects of UIAP breadth on company growth. Furthermore, the results show that government subsidies weaken the negative relationship between UIAP depth and NTBF growth, along with the positive relationship between UIAP breadth and NTBF growth. By contributing to previous research on alliance portfolios, university–industry collaborations, and firm growth; this study provides some practical implications for both industry practitioners and policymakers in emerging economies.Zeraatkar & Moghaddasi (2022) investigated the mediation model of business intelligence in the relationship between process innovation and organizational performance. According to the studies carried out, it shows the fact that hotel management must have strong points such as having specialized and specialized human resources, having specialized medical facilities, having natural resources and attractions, tourism infrastructure, transportation, etc. and the results indicate that process innovation has an impact on business intelligence, and also business intelligence through process innovation has an impact on organizational performance.Research MethodologyThis research is applicable in terms of purpose, quantitative in terms of data collection, and thematic analysis research in terms of research implementation method. To collect information, the fuzzy Delphi method was used in three rounds to find the use of business intelligence to improve the relationship between the university and the industry. The statistical population of this research consists of 12 professors and specialists in the field of communication with industry and, selected using the available method; and primary dimensions, components and indicators were compiled by using the field method and semi-structured interview tool. After analyzing the interviews, a total of 5 dimensions and 57 indicators were identified in line with the research objectives.Research FindingsData analysis was done using MAXQDA 2018 software. Based on the obtained results and according to the qualitative analysis, a total of 7 dimensions and 57 indicators have been identified and confirmed. The results showed that the dimensions of using business intelligence to improve the relationship between university and industry include the first layer/preparation of the environment, the second layer/data collection, the third layer/ETL (extraction, transfer, loading of data), the fourth layer/warehousing, and the fifth layer/user interface (UI), metadata management and change management.ConclusionThe current research has been carried out with the aim of identifying the dimensions (layers) of a framework for applying business intelligence to improve the relationship between university and industry. The results of this research are in agreement with the results of Zhang et al, (2020), Zhang et al, (2022), Basile et al, (2021), Paradza & Daramola (2021), Caloghirou et al, (2021) and Hoseinloo et al, (2021). Zhang et al, (2020) states that BI readiness makes it possible for the organization to recognize its current situation and prepare to make changes. In this layer, along with reviewing and analyzing the current situation, designing and planning is done for the process of technology transfer from university to industry, which is a basis for establishing intelligent business communication between university and industry. Also, the factors affecting the said transfer process are examined. At this stage, proper management of processes, budget allocation, hardware and software resources, skill requirements, and training of employees are provided in order to prepare the conditions for the implementation of BI architecture.Based on the obtained results, it is suggested for business intelligence to improve communication between university and industry by providing groups with extensive databases to transfer information faster and more accurately.Based on the obtained results, it is suggested for business intelligence to improve the communication between the university and the information by information verification and refining the complete compatibility of software and hardware by applying a strong filter so that more accurate information is available

Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action

Among malignancies, lung cancer is the major cause of cancer death. Despite the advance in lung cancer therapy, the five-year survival rate is extremely restricted due to therapeutic failure and disease relapse. Targeted therapies selectively inhibiting certain molecules in cancer cells have been accepted as promising ways to control cancer. In lung cancer, evidence has suggested that the myeloid cell leukemia 1 (Mcl-1) protein, an anti-apoptotic member of the Bcl-2 family, is a target for drug action. Herein, we report the Mcl-1 targeting activity of renieramycin T (RT), a marine-derived tetrahydroisoquinoline alkaloid that was isolated from the Thai blue sponge Xestospongia sp. RT was shown to be dominantly toxic to lung cancer cells compared to the normal cells in the lung. The cytotoxicity of this compound toward lung cancer cells was mainly exerted through apoptosis induction. For the mechanism of action, we found that RT mediated activation of p53 protein and caspase-9 and -3 activations. While others Bcl-2 family proteins (Bcl-2, Bak, and Bax) were minimally changed in response to RT, Mcl-1 protein was dramatically diminished. We further performed the cycloheximide experiment and found that the half-life of Mcl-1 was significantly shortened by RT treatment. When MG132, a potent selective proteasome inhibitor, was utilized, it could restore the Mcl-1 level. Furthermore, immunoprecipitation analysis revealed that RT significantly increased the formation of Mcl-1-ubiquitin complex compared to the non-treated control. In conclusion, we report the potential apoptosis induction of RT with a mechanism of action involving the targeting of Mcl-1 for ubiquitin-proteasomal degradation. As Mcl-1 is critical for cancer cell survival and chemotherapeutic failure, this novel information regarding the Mcl-1-targeted compound would be beneficial for the development of efficient anti-cancer strategies or targeted therapies

5-<i>O</i>-Acetyl-Renieramycin T from Blue Sponge <i>Xestospongia</i> sp. Induces Lung Cancer Stem Cell Apoptosis

Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor. The discovery of novel compounds able to suppress CSCs and sensitize the chemotherapeutic response could be beneficial to the improvement of clinical outcomes. Herein, we report for the first time that 5-O-acetyl-renieramycin T isolated from the blue sponge Xestospongia sp. mediated lung cancer cell death via the induction of p53-dependent apoptosis. Importantly, 5-O-acetyl-renieramycin T induced the death of CSCs as represented by the CSC markers CD44 and CD133, while the stem cell transcription factor Nanog was also found to be dramatically decreased in 5-O-acetyl-renieramycin T-treated cells. We also found that such a CSC suppression was due to the ability of the compound to deplete the protein kinase B (AKT) signal. Furthermore, 5-O-acetyl-renieramycin T was able to significantly sensitize cisplatin-mediated apoptosis in the lung cancer cells. Together, the present research findings indicate that this promising compound from the marine sponge is a potential candidate for anti-cancer approaches