"Show this thread": policing, disruption and mobilisation through Twitter. An analysis of UK law enforcement tweeting practices during the Covid-19 pandemic

Crisis and disruption are often unpredictable and can create opportunities for crime. During such times, policing may also need to meet additional challenges to handle the disruption. The use of social media by officials can be essential for crisis mitigation and crime reduction. In this paper, we study the use of Twitter for crime mitigation and reduction by UK police (and associated) agencies in the early stages of the Covid-19 pandemic. Our findings suggest that whilst most of the tweets from our sample concerned issues that were not specifically about crime, especially during the first stages of the pandemic, there was a significant increase in tweets about fraud, cybercrime and domestic abuse. There was also an increase in retweeting activity as opposed to the creation of original messages. Moreover, in terms of the impact of tweets, as measured by the rate at which they are retweeted, followers were more likely to ‘spread the word’ when the tweet was content-rich (discussed a crime specific matter and contained media), and account holders were themselves more active on Twitter. Considering the changing world we live in, criminal opportunity is likely to evolve. To help mitigate this, policy makers and researchers should consider more systematic approaches to developing social media communication strategies for the purpose of crime mitigation and reduction during disruption and change more generally. We suggest a framework for so doing

Cyrillic Manuscript Heritage: Vol. 38

CMH 38 cover design based on the cover design of CMH 34 created by Eva Dujardin Dale.Biannual newsletter of the Hilandar Research Library (HRL) and the Resource Center for Medieval Slavic Studies (RCMSS), The Ohio State University. Includes: features by guest contributors, which may appear under the column heading of "HRL Journal" – where Cyrillic Manuscript Heritage asks researchers who have used the resources of the HRL in the past year to describe their experience and work; a column, "Director's Desk," by the Director of RCMSS; "RCMSS & HRL News Notes," i.e., reports on recent visitors, research, events, exhibits, projects, updates, etc.; contributors to both the Hilandar Endowment Fund and Hilandar's Friends of the Library Fund are listed, as are donors of "Gifts in Kind." Also included may be seasonal announcements regarding the International Hilandar Conference series and the Medieval Slavic Summer Institute.Front cover image: SPEC.OSU.HRL.GMS.FRAG.2, two sides of a single vellum leaf from a Byzantine Greek Gospel lectionary, purchased by the HRL with donations made to the Hilandar Endowment Fund and Hilandar Friends of the Library funds by Frances Roslovic, the Ostich Family, and Sharon Fullerton Maliska; Table of Contents, masthead, front cover photo caption, p. 2; "From the Director's Desk" by Dr. Predrag Matejic, p. 3; "Our Visitors": "A Blast from the Past," photo by Jessi Jones, "A Family Affair" and "HRL Public Lecture on Ivan the Terrible," photos by Jessi Jones, and photo by Georgios Anagnostou of Dr. William Kaldis and his daughter Maria Kaldis Arend, p. 4; "A Special Chaplains' Visit to the HRL" and "An Undergraduate Class Visit," photos by Jessi Jones, p. 5; "All in the Family: A Research Visit from an Alumna of MSSI 2001" by Monica White, photo courtesy of M. White, pp. 6, 8; "'Approaches to the Editing of Slavonic Texts' Workshop in Regensburg, Germany" by Susana Torres Prieto, photos courtesy of S. Torres Prieto, pp. 7-8; Unnumbered insert: recto - "In Memoriam: Professor Charles Edward Gribble," based on an obituary written by Daniel E. Collins, photo courtesy of the OSU department of Slavic and East European Languages and Cultures, and verso: Medieval Slavic Summer Institute 2017 announcement, photos by Jessi Jones; "HRL Journal: Accessing the Forbidden" by Kristina Nikolovska, photo courtesy of K. Nikolovska, p. 9; "Catching up with our MSSI Alumni," photos courtesy of Michael Furman, Alice Sullivan, and Federica Candido, p. 10; "HRL Journal: Examining the Serbian Euchologion" by Tatiana Afanas'eva, photo courtesy of T. Afanas'eva, p. 11; "HRL Journal: My First Trip to the U.S." by Marta Peña Escudero, photos courtesy of M. Peña Escudero, pp. 12, 14; "Manuscript Marginalia Lecture by Dr. Nikolovska," photo by Jessi Jones, p. 13; "A Step into Sociology: Slovene Scholars' Lecture," photos by Jessi Jones, p. 13; "In Memoriam: Protinica Ljubica Matejic," photo courtesy of Nenad Matejic, p. 14; Contributions to the Hilandar Endowment Fund, Gifts through Friends of the Library, and Gifts-in-Kind to the Hilandar Research Library, p. 15; back cover, birth announcement of Predrag Matejic's granddaughter, Elisaveta Todora Matejic, photo courtesy of Svetoslav and Sarah Matejic

Analyses of Ligand Binding to IP3 Receptors Using Fluorescence Polarization.

Fluorescence polarization (FP) can be used to measure binding of a small fluorescent ligand to a larger protein because the ligand rotates more rapidly in its free form than when bound. When excited with plane polarized light, the free fluorescent ligand emits depolarized light, which can be quantified. Upon binding, its rotation is reduced and more of the emitted light remains polarized. This allows FP to be used as a nondestructive assay of ligand binding. Here we describe a fast, high-throughput FP assay to quantify the binding of fluorescently labeled inositol 1,4,5-trisphosphate (IP3) to N-terminal fragments of the IP3 receptor. The assay is fast (1-6 h), it avoids use of radioactive materials and when measurements are performed at different temperatures, it can resolve Gibbs free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) changes of ligand binding

Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib

BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is an anti-apoptotic protein exerting its activity by binding and suppressing caspases. As XIAP is overexpressed in several tumours, in which it apparently contributes to chemoresistance, and because its activity in vivo is antagonised by second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis-binding protein with low pI, small molecules mimicking SMAC (so called SMAC-mimetics) can potentially overcome tumour resistance by promoting apoptosis. METHODS: Three homodimeric compounds were synthesised tethering a monomeric SMAC-mimetic with different linkers and their affinity binding for the baculoviral inhibitor repeats domains of XIAP measured by fluorescent polarisation assay. The apoptotic activity of these molecules, alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or Bortezomib, was tested in melanoma cell lines by MTT viability assays and western blot analysis of activated caspases. RESULTS: We show that in melanoma cell lines, which are typically resistant to chemotherapeutic agents, XIAP knock-down sensitises cells to TRAIL treatment in vitro, also favouring the accumulation of cleaved caspase-8. We also describe a new series of 4-substituted azabicyclo[5.3.0] alkane monomeric and dimeric SMAC-mimetics that target various members of the IAP family and powerfully synergise at submicromolar concentrations with TRAIL in inducing cell death. Finally, we show that the simultaneous administration of newly developed SMAC-mimetics with Bortezomib potently triggers apoptosis in a melanoma cell line resistant to the combined effect of SMAC-mimetics and TRAIL. CONCLUSION: Hence, the newly developed SMAC-mimetics effectively synergise with TRAIL and Bortezomib in inducing cell death. These findings warrant further preclinical studies in vivo to verify the anticancer effectiveness of the combination of these agents

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year

Development of Peptidomimetics Targeting IAPs

Inhibitor of apoptosis proteins (IAPs) such as XIAP subvert apoptosis by binding and inhibiting caspases. Because occupation of the XIAP BIR3 peptide binding pocket by Smac abolishes the XIAP–caspase 9 interaction, it is a proapoptotic event of great therapeutic interest. An assay for pocket binding was developed based on the displacement of Smac 7-mer from BIR3. Through the physical and biochemical analysis of a variety of peptides, we have determined the minimum sequence required for inhibition of the Smac–BIR3 interaction and detailed the dimensions and topology of the BIR3 peptide binding pocket. This work describes the structure–activity relationship (SAR) for peptide inhibitors of Smac-IAP binding

Use of SEM/EDX methods for the analysis of ambient particulate matter adhering to the skin surface

Background The skin is exposed to numerous particulate and gaseous air pollutants. The ones that need particular attention are the particles that adhere to the skin surface, which can later cause direct skin damage. This study aimed to characterize air pollution (AP) particles adhered to the human skin by using scanning electron microscopy (SEM) combined with X-ray dispersive energy spectrometry (EDX). Methods Tape stripping was performed from six healthy volunteers exposed to urban AP to collect stratum corneum samples from the cheeks and forehead. The samples were analysed using SEM equipped with EDX system with a silicon drift detector at an accelerating voltage of 20 keV. After the preliminary examination, the particles were located and counted using 1000× magnification. Each particle was analysed, increasing magnification up to 5000× for precise dimension measurement and elemental composition analysis. At least 100 fields or a surface of approximately 1 mm2 were examined. Results Particles adhered to the skin were identified in all samples, with a particle load ranging from 729 to 4525. The average area and perimeter of all particles identified were 302 ± 260 μm2 and 51 ± 23 μm subsequently, while the equivalent circular diameter was, on average, 14 ± 6 μm. The particles were classified into ten groups based on morphology and elemental composition. Chlorides were the most numerous particle group (21.9%), followed by carbonaceous organic particles (20.3%), silicates (18%), carbonates (16.4%), metal-rich particles (14%), and a minor number of bioaerosols, quartz-like, and fly ash particles. Conclusion The SEM–EDX analysis provides evidence of the contamination of exposed skin to various airborne PM of natural or anthropogenic origin. This method may provide new insights into the link between exposure to AP and AP-induced skin damage

The Apoptosome: Emerging Insights and New Potential Targets for Drug Design

Apoptosis plays a crucial role in tissue homeostasis, development and many diseases. The relevance of Apaf1, the molecular core of apoptosome, has been underlined in mitochondria-dependent apoptosis, which according to a growing body of evidence, is involved in various pathologies where the equilibrium of life-and-death is dysregulated, such as heart attack, stroke, liver failure, cancer and autoimmune diseases. Consequently, great interest has emerged in devising therapeutic strategies for regulating the key molecules involved in the life-and-death decision. Here we review recent progress in apoptosis-based pharmacological therapies and, in particular, we point out a possible role of the apoptosome as an emerging and promising pharmacological target