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There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure–activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.

Purpose: The purpose of this paper is to undertake an exploratory study on mapping the investment fraud methods and tactics used by scammers against the emerging literature on scam compliance. Design/methodology/approach: Qualitative interviews were conducted with victims of investment fraud supported by the engagement of specialist counsellors and allied health professionals who specialise in scam victim support (including investment fraud). Findings: Investment fraud offending in the cases sampled exhibited a number of dominant offending traits and methodological themes. These included a strong reliance or dependency on legitimate service provisioning on the part of the fraudster and the use of key trust measures to lure the victim. The empirical data revealed the presence of a number of scam compliance influences captured in the literature, including trust, social influence and urgency, as well as others not previously documented that pave the way for further research attention. Research limitations/implications: The research only examined a sample of investment fraud victim experiences that engaged a national victim support service immediately following detection over a 24 month period. Practical implications: The research found that offending relied upon the participation of trust-building signals and measures. Legitimate economy participants appear to play a dominant role in enabling investment scam activities, further creating efficiencies for criminals. The offending tended to follow a number of distinct but connected phases. Impacts were influenced by specific offending attributes, such as whether remote access was given to offenders of a victim’s device, as well as the nature of the identity credentials access. Originality/value: The research has practically applied an emerging view of scam compliance influences and vulnerabilities within an investment fraud context. The study is novel in its thematic analysis of the distinct phases and tactics used by sca

The reactivity and synthesis of new analogues of pyrido[1,2-a]benzimidazoles have been explored. Twenty-three derivatives bearing phenoxy, thiophenoxy, aniline, and aryl groups at the 1-position were successfully synthesised in 25-91 % yield, via nucleophilic substitution, Buchwald-Hartwig amination, and Suzuki coupling type processes. Solvent free synthetic protocols were employed to achieve the nucleophilic substitution of anilines with electron donating groups or moderately electron withdrawing groups on a sterically demanding intermediate (7a). An unusual polycyclic heterocycle was identified as a side-product during this work: a dimeric bis(pyrido[1,2-a]benzimidazole).

INTRODUCTION: The global COVID-19 pandemic forced the cancellation of the TROG 2020 face to face Annual Scientific Meeting (ASM). It was instead delivered as a live virtual meeting with 6 days of planning. Here, we report the participants' experience of this live virtual meeting. METHOD: Participants were invited to complete custom-developed, pre- and post-meeting surveys to assess their expectations of and satisfaction with the live virtual format. Speakers and moderators were also invited to complete a custom-developed satisfaction survey. The working parties of TROG (head/neck/skin, genitourinary, breast and lung) were also sampled. RESULTS: In total, 188/273 (69%) registered participants logged in to the live virtual meeting. The online engagement for each of the oral sessions ranged from 53 to 66%. There were 102 and 57 responders to the online pre- and post-meeting surveys, respectively. The majority of pre-meeting responders indicated a significant level of employer support to attend the virtual meeting. Post-meeting satisfaction exceeded pre-meeting expectations ('very much' and 'quite a bit'; 86% vs. 54%; P < 0.0001). The majority indicated they would be 'quite a bit' or 'very much' interested in future live virtual meetings. CONCLUSION: The TROG 2020 ASM was conducted as a live virtual meeting. Participant satisfaction and future interest in a live virtual meeting was high, indicating this is a viable platform for other CCTG's faced with the decision to deliver virtual content at times of global public health threats.

The dysregulation of macrophage lipid metabolism drives atherosclerosis. AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics and plays essential roles regulating macrophage lipid dynamics. Here, we investigated the consequences of atherogenic lipoprotein-induced foam cell formation on downstream immunometabolic signaling in primary mouse macrophages. A variety of atherogenic low-density lipoproteins (acetylated, oxidized, and aggregated forms) activated AMPK signaling in a manner that was in part due to CD36 and calcium-related signaling. In quiescent macrophages, basal AMPK signaling was crucial for maintaining markers of lysosomal homeostasis as well as levels of key components in the lysosomal expression and regulation network. Moreover, AMPK activation resulted in targeted upregulation of members of this network via transcription factor EB. However, in lipid-induced macrophage foam cells, neither basal AMPK signaling nor its activation affected lysosomal-associated programs. These results suggest that while the sum of AMPK signaling in cultured macrophages may be anti-atherogenic, atherosclerotic input dampens the regulatory capacity of AMPK signaling.

Biolistic delivery of biomolecular cargoes to plants with micron-scale projectiles is a well-established technique in plant biotechnology. However, the relatively large micron-scale biolistic projectiles can result in tissue damage, low regeneration efficiency, and create difficulties for the biolistic transformation of isomorphic small cells or subcellular target organelles (i.e., mitochondria and plastids). As an alternative to micron-sized carriers, nanomaterials provide a promising approach for biomolecule delivery to plants. While most studies exploring nanoscale biolistic carriers have been carried out in animal cells and tissues, which lack a cell wall, we can nonetheless extrapolate their utility for nanobiolistic delivery of biomolecules in plant targets. Specifically, nanobiolistics has shown promising results for use in animal systems, in which nanoscale projectiles yield lower levels of cell and tissue damage while maintaining similar transformation efficiencies as their micron-scale counterparts. In this chapter, we specifically discuss biolistic delivery of nanoparticles for plant genetic transformation purposes and identify the figures of merit requiring optimization for broad-scale implementation of nanobiolistics in plant genetic transformations.

This protocol presents a detailed procedure for the operation of continuous, micron-sized cryogenic cylindrical and planar liquid jets. When operated as described here, the jet exhibits high laminarity and stability for centimeters. Successful operation of a cryogenic liquid jet in the Rayleigh regime requires a basic understanding of fluid dynamics and thermodynamics at cryogenic temperatures. Theoretical calculations and typical empirical values are provided as a guide to design a comparable system. This report identifies the importance of both cleanliness during cryogenic source assembly and stability of the cryogenic source temperature once liquefied. The system can be used for high repetition rate laser-driven proton acceleration, with an envisioned application in proton therapy. Other applications include laboratory astrophysics, materials science, and next-generation particle accelerators.