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Discovery of Benzopyrone-Based Candidates as Potential Antimicrobial and Photochemotherapeutic Agents through Inhibition of DNA Gyrase Enzyme B: Design, Synthesis, In Vitro and In Silico Evaluation
Get PDFBacterial DNA gyrase is considered one of the validated targets for antibacterial drug discovery. Benzopyrones have been reported as promising derivatives that inhibit bacterial DNA gyrase B through competitive binding into the ATP binding site of the B subunit. In this study, we designed and synthesized twenty-two benzopyrone-based derivatives with different chemical features to assess their antimicrobial and photosensitizing activities. The antimicrobial activity was evaluated against B. subtilis, S. aureus, E. coli, and C. albicans. Compounds 6a and 6b (rigid tetracyclic-based derivatives), 7a-7f (flexible-linker containing benzopyrones), and 8a-8f (rigid tricyclic-based compounds) exhibited promising results against B. subtilis, S. aureus, and E. coli strains. Additionally, these compounds demonstrated photosensitizing activities against the B. subtilis strain. Both in silico molecular docking and in vitro DNA gyrase supercoiling inhibitory assays were performed to study their potential mechanisms of action. Compounds 8a-8f exhibited the most favorable binding interactions, engaging with key regions within the ATP binding site of the DNA gyrase B domain. Moreover, compound 8d displayed the most potent IC50 value (0.76 μM) compared to reference compounds (novobiocin = 0.41 μM and ciprofloxacin = 2.72 μM). These results establish a foundation for structure-based optimization targeting DNA gyrase inhibition with antibacterial activity
Investing in resources: An interaction model of personal resources, commitment, and work achievement
No full textObjectiveManagement practice commonly assumes that the value of a work-goal dictates the nature of motivation processes. We investigate instead how individuals invest resources from the perspective of their own value system. Drawing from Conservation of Resources theory, we explore the valuation process by testing a reciprocal model between work-goal attainment, goal commitment, and personal resources, including self-efficacy, optimism, and subjective well-being.MethodData were collected in a two-wave longitudinal study among sales professionals (n = 793) from France (F), Pakistan (P), and the United States (U).ResultsMulti-group cross-lagged path analysis confirmed the reciprocal model across all three countries. Time 1 resources and goal commitment predicted work goal attainment (F = 0.24; P = 0.37; U = 0.39) and (F = 0.31; P = 0.40; U = 0.36) respectively. T1 level of goal attainment also fuelled T2 resources and goal commitment (F = 0.30; P = 0.29; U = 0.34) and (F = 0.33; P = 0.32; U = 0.29).ConclusionsOur reciprocal findings suggest a revised approach on the nature of targets and goals. They indicate an alternative to linear path modeling, as the role of goal commitment is not necessarily that of an intermediary stage linking antecedent resources to attainment purposes. Furthermore, cultural values play a differentiating role in the goal-attainment process
Moving Healthcare AI Support Systems for Visually Detectable Diseases to Constrained Devices
Get PDFImage classification usually requires connectivity and access to the cloud, which is often limited in many parts of the world, including hard-to-reach rural areas. Tiny machine learning (tinyML) aims to solve this problem by hosting artificial intelligence (AI) assistants on constrained devices, eliminating connectivity issues by processing data within the device itself, without Internet or cloud access. This study explores the use of tinyML to provide healthcare support with low-spec devices in low-connectivity environments, focusing on the diagnosis of skin diseases and the ethical use of AI assistants in a healthcare setting. To investigate this, images of skin lesions were used to train a model for classifying visually detectable diseases (VDDs). The model weights were then offloaded to a Raspberry Pi with a webcam attached, to be used for the classification of skin lesions without Internet access. It was found that the developed prototype achieved a test accuracy of 78% when trained on the HAM10000 dataset, and a test accuracy of 85% when trained on the ISIC 2020 Challenge dataset
Editorial: Rethinking Anti-Trafficking Funding: Following the money, again
Get PDFThis Editorial introduces a special issue of the Anti-Trafficking Review that investigates where the funding for anti-trafficking work comes from, goes to, and with what effect. It reflects on some of the changes in funding that have occurred over the past ten years and why it is necessary to research and analyse these changes. It then introduces the articles in the special issue and concludes with suggestions for future research on the topic
Masters: The Invisible War of the Powerful Against Their Subjects
No full textIn his book "Masters: The Invisible War of the Powerful Against Their Subjects", Marco D’Eramo, journalist and social thinker, navigates the reader through the war that the powerful have unleashed against the people. The book includes a contingent plan and an abundance of resources, while critiquing the contemporary left for failing to stand up to the circumstances. The book astutely delves into families behind the ‘capitalist revolutions’ and ‘counterrevolutions’ against people’s vested rights. D’Eramo exposes how charity organisations and foundations manipulated progressive US laws in the early 20th century to evade corporate taxes, ultimately operating far from nonprofit motives. The book is flooded with evidence over the entanglement between the state and the most conservative parts of American capital, dispelling the notion that the state shrinks under neoliberalism—arguing that it in fact, becomes gigantic and more oppressive. A recurring theme is the portrayal of 20th and 21st century ‘democratic’ and ‘free’ developed capitalist economies through a history of environmental, health, human trafficking, and murderous scandals. This plethora of attacks that the powerful have employed - in what the author concludes to be a class war between capitalists and the people - is shocking but not surprising. This book reminds us how inhumane economics and particularly Neoclassical, New Classical and Austrian economics can be. With examples such as the economics of the ‘baby market’ readers are horrified to be remembered of analyses such as Posner’s on setting prices on the infants and the risks of the baby as a commodity that cannot be returned if they are defective. The book scrutinises similar contributions such as the Coase theorem and ‘the optimal level of pollution’ (pervasive in environmental economics teaching). D’Eramo is shining a light on the economic discipline’s objectification of people and the environment frequently witnessed, not as a mistake but a conscious choice of a system of ideas, tools, and methods.D'Eramo also offers a fervent critique of the contemporary left, accusing it of being Thatcherite, based on a TINA (There Is No Alternative) doctrine, having accepted their defeat by restricting their ‘alternatives’ within the boundaries of the capitalist system itself. The book is pointing out the triumph of the capitalist class of being more consistent in securing successful revolutions, even in accordance with the lessons of Lenin and Gramsci – but for the opposite class, that of the masters! However, having knowledge, but written from outside the discipline of economics, D’Eramo’s puts ideas, ideology and the capitalist inteligencia in the forefront, as if these are that run the world. D’Eramo could have enhanced the book by bringing up the real-life problems faced by capitalists in the late 60s and 70s, with their falling rates of profit, and reproduction, and accumulation. Despite the usefulness of a Keynesian management of capitalist economies in previous decades, falling rates of profit and subsequent capitalist crisis appeared inevitable, forcing capitalists to re-evaluate their mode of accumulation, restructure economy’s sectors and launch relevant ideologies to the people. It would not come as a surprise if the end of neo-liberalism comes with a New 21st century Deal, restructuring capitalism afresh, only to save the once again falling rates of profit and the accumulation process; both expansionary and contractionary economic policies aim to serve the survival of the capitalist system and its exploitative nature.Although mentioned, it is not a central point that neoliberalism, with its effortless infiltration to the traditional (social)-democratic parties is related to the demise of the USSR at that time. Western capitalism, by having a rival socialist awe – even with its many problems – was a significant factor to think twice, and thrice before attacking peoples’ vested rights. This also explains the ruthlessness of the "masters’" attacks and the weakness of the western left by demanding a longer chain for the subjects instead of its complete abolition. In conclusion, this war is not invisible after all. D’Eramo, with optimism of both intellect and will, concludes his book with Macchiavelli’s saying that ‘good laws arise from tumults’ (p. 233), suggesting that the subjects should proceed, and not being afraid of revolts and revolutions
Out There
No full textOut There is a graphic novel adapted from a screenplay written by Ronnie Mackintosh and in development with production company Nickie-Ben
Designing with Cross Laminated Timber (CLT)
No full textThe development of CLT brought new possibilities for timber in construction. Instead of framing smaller timber sections to form load-bearing structural systems, timber products using CLT can form walls and roofs of structures in large surface panels.Thanks to high-precision prefabrication, CLT elements can be assembled quickly and easily, often using traditional methods such as screwing or nailing
The Vitruvian nurse and burnout: New materialist approaches to impossible ideals
Get PDFThe Vitruvian Man is a metaphor for the “ideal man” by feminist posthuman philosopher Rosi Braidotti (2013) as a proxy for eurocentric humanist ideals. The first half of this paper extends Braidotti's concept by thinking about the metaphor of the “ideal nurse” (Vitruvian nurse) and how this metaphor contributes to racism, oppression, and burnout in nursing and might restrict the professionalization of nursing. The Vitruvian nurse is an idealized and perfected form of a nurse with self-sacrificial language (re)producing self-sacrificing expectations. The second half of this paper looks at how regulatory frameworks (using the example of UK's Nursing and Midwifery Council Code of Conduct) institutionalize the conditions of possibility through collective imaginations. The domineering expectations found within the Vitruvian nurse metaphor and further codified by regulatory frameworks give rise to boredom and burnout. The paper ends by suggesting possible ways to diffract regulatory frameworks to practice with affirmative ethics and reduce feelings of self-sacrifice and exhaustion among nurses
Glued Laminated Timber (Glulam)
No full textGlued Laminated Timber, commonly referred to as glulam or GLT, comprises several layers of dimensioned, strength-graded timber bonded together with structural adhesive to increase structural performance. It is one of several systems that connect a series of smaller timber elements together to form larger panel or beam products
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