A new paradigm for simulating pulse-like ruptures: the pulse energy equation

We investigate the chaotic behaviour of slip pulses that propagate in a spring block slider model with velocity weakening friction by numerically solving a computationally intensive set of n coupled non-linear equations, where n is the number of blocks. We observe that the system evolves into a spatially heterogeneous pre-stress after the occurrence of a sufficient number of events. We observe that, although the spatiotemporal evolution of the amplitude of a slip pulse in a single event is surprisingly complex, the geometric description of the pulses is simple and self-similar with respect to the size of the pulse. This observation allows us to write an energy balance equation that describes the evolution of the pulse as it propagates through the known pre-stress. The equation predicts the evolution of individual ruptures and reduces the computational time dramatically. The long-time solution of the equation reveals its multiscale nature and its potential to match many of the long-time statistics of the original system, but with a much shorter computational time

CHEMICAL INVESTIGATION OF BAUHINIA VAHLII WIGHT AND ARNOTT LEAVES GROWN IN EGYPT

Objective: Plants of genus Bauhinia are famous for their rich flavonoid content. Several phytochemical and biological investigations affirmed the role of flavonoids in the different biological impacts exerted by Bauhinia plants. The present study aims to investigate the major phytoconstituents of the leaves of B. vahlii Wight and Arnott.Methods: Powdered leaves were extracted with n-hexane (HE) and the defatted marc was extracted with 70% ethanol. The defatted ethanolic extract (DEE) was further partitioned with solvents of increasing polarities. The HE and polar fractions of DEE were purified using different chromatographic techniques and isolated compounds were identified through their melting points, 1D and 2D NMR, UV and MS spectral data.Results: A total of nine compounds were isolated and identified. Taraxerol (1), a pentacyclic triterpene, and β-sitosterol (2) were isolated from HE. Investigation of polar fractions of DEE yielded six flavonoids and a phenolic acid, namely luteolin (3), quercetin (4), gallic acid (5), avicularin (6), quercitrin (7), hyperoside (8) and quercetin-3-O-β-sophoroside (9).Conclusion: Flavonols of the quercetin nucleus were the major detected constituents in B. vahlii leaves. Taraxerol, avicularin and quercetin-3-O-β-sophoroside are isolated for the first time from the genus Bauhinia. Results of this study encourage future pharmacological investigation of B. vahlii due to the presence of biologically active flavonoids and phytosterols.Keywords: Bauhinia vahlii Wight, Arnott., Polar extractives, Flavonols, Quercetin, TaraxerolÂ

Assessing disparities in medical students’ knowledge and attitude about monkeypox: a cross-sectional study of 27 countries across three continents

Background and aimsThe recent monkeypox (Mpox) outbreak confirmed by the World Health Organization (WHO) underscores the importance of evaluating the knowledge and attitude of medical students toward emerging diseases, given their potential roles as healthcare professionals and sources of public information during outbreaks. This study aimed to assess medical students’ knowledge and attitude about Mpox and to identify factors affecting their level of knowledge and attitude in low-income and high-income countries.MethodsA cross-sectional study was conducted on 11,919 medical students from 27 countries. A newly-developed validated questionnaire was used to collect data on knowledge (14 items), attitude (12 items), and baseline criteria. The relationship between a range of factors with knowledge and attitude was studied using univariate and multivariate analyses.Results46% of the study participants were males; 10.7% were in their sixth year; 54.6% knew about smallpox; 84% received the coronavirus disease 2019 (COVID-19) vaccine; and 12.5% had training on Mpox. 55.3% had good knowledge of Mpox and 51.7% had a positive attitude towards it. Medical students in their third, fifth, or sixth year high- income countries who obtained information on Mpox from friends, research articles, social media and scientific websites were positive predictors for good knowledge. Conversely, being male or coming from high-income countries showed a negative relation with good knowledge about Mpox. Additionally, a positive attitude was directly influenced by residing in urban areas, being in the fifth year of medical education, having knowledge about smallpox and a history of receiving the coronavirus disease 2019 (COVID-19) vaccine. Receiving information about Mpox from social media or scientific websites and possessing good knowledge about Mpox were also predictors of a positive attitude. On the other hand, being male, employed, or receiving a training program about Mpox were inversely predicting positive attitude about Mpox.ConclusionThere were differences in knowledge and attitude towards Mpox between medical students in low and high-income countries, emphasizing the need for incorporating epidemiology of re-emerging diseases like Mpox into the medical curriculum to improve disease prevention and control

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin’s cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm−2.h−1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy

Scopularides Revisited: Molecular Networking Guided Exploration of Lipodepsipeptides in Australian Marine Fish Gastrointestinal Tract-Derived Fungi

Chemical analysis of a cultivation of an Australian Mugil mullet gastrointestinal tract (GIT) derived fungus, Scopulariopsis sp. CMB-F458, yielded the known lipodepsipeptides scopularides A (1) and B (2). A comparative global natural product social (GNPS) molecular networking analysis of ×63 co-isolated fungi, detected two additional fungi producing new scopularides, with Beauveria sp. CMB-F585 yielding scopularides C–G (3–7) and Scopulariopsis sp. CMB-F115 yielding scopularide H (8). Structures inclusive of absolute configurations were assigned by detailed spectroscopic and C3 Marfey’s analysis, together with X-ray analyses of 3 and 8, and biosynthetic considerations. Scopularides A–H (1–8) did not exhibit significant growth inhibitory activity against a selection of Gram positive (+ve) and negative (−ve) bacteria, a fungus, or a panel of three human carcinoma cell lines

Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214

Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A–D (11–14) in addition to a suite of very minor aza analogues 1–6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1–6; however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines; chrysosporazines N–P (7–9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1–15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1–5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2′ substituted analogues 3–5

Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi

A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation amplified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300)

The use of performance information in strategic decision making in public organizations

Purpose – The purpose of this paper is to investigate how the importance of different components of strategic performance measurement systems (SPMS) and their deployment influence the use of performance information from the SPMS in making strategic decisions. Design/methodology/approach – Data were collected through a survey of 143 managers of Canadian public organizations. Findings – The findings indicate that two SPMS components, namely, the importance of non-financial performance measures and the use of operational efficiency measures, have significant positive associations with performance information use for strategy implementation and strategy assessment decisions. The extent to which SPMS models were used is found to be positively associated with performance information use for strategy implementation, but not for strategy assessment, decisions. Furthermore, the relationships between SPMS variables and strategic decision making are moderated by information systems/data limitations and management’s commitment to attaining strategic goals. Managerial skills acquired through training or experience with SPMS also contribute positively to such relationships. Research limitations/implications – The results are affected by limitations associated with the survey method used. Practical implications – The findings could be useful for supporting public policy, strategic decision making, public service improvement, operational efficiency, and effectiveness. Originality/value – The study contributes to public management and performance measurement literature by investigating multiple determinants of performance information use in a cross-section of Canadian public organizations