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Food and peace? Exploring the link between conflict and food insecurity in Africa
This paper contributes to the literature on the costs of conflict, focusing on the important channel of its effect on food security. It does this by examining whether people in conflict zones lack sufficient food and whether this can be directly attributed to armed conflicts. It uses the Afrobarometer household survey and data from the Armed Conflict Location and Event Data Project (ACLED) for conflict indicators, specifically, the number of battle-related events at the regional level. The dataset spans 2012–2022 across 29 African countries. The effect of battle-related events (i.e. battle deaths) on food insecurity is evaluated using a two-way fixed effect and a weighted regression framework that directly addresses unobserved heterogeneity. The model shows that a rise in battle-related events in a region leads to increased food insecurity and this result is found to be robust. When more intense food insecurity is considered, conflict is also found to have an even larger effect. This provides evidence that conflict has a significant impact on food security in Africa. This has important health implications and adds to the evidence of the important legacy costs of conflict that can last long after the conflict ends
Interaction Between Ionic Liquids and Lipid Membranes: A Comparative Analysis of the Mechano-Elastic Properties of Membranes as a Function of the Molecular Structure of Ionic Liquids Using Atomic Force Microscopy
This dissertation investigates the intricate interactions between ionic liquids (ILs) and cell membranes, employing dimyristoylphosphatidylcholine (DMPC) lipid bilayers as a model biomembrane. The research focuses on the mechano-elastic properties of lipid bilayers and examines how these properties are influenced by the molecular structures of three ILs: 1 butyl-3-methylimidazolium chloride tetrachloroferrate ([bmim][FeCl4]), ([bmim][Cl]), 1-butyl-3-methylimidazolium and 1-decyl-3-methylimidazolium chloride ([dmim][Cl]). Advanced atomic force microscopy (AFM) methodologies, including force spectroscopy and off-resonance imaging, were utilised to generate high-resolution data on bilayer morphology and mechanical properties. By leveraging AFM, the study elucidates the effects of variations in cation alkyl chain length and anion size on membrane stability, fluidity, elasticity and rupture force. The ILs investigated demonstrate distinctive impacts on the DMPC lipid bilayer. [bmim][Cl] and [bmim][FeCl4], which share the same cation, induce comparable destabilising effects, such as decreasing in rupture force and increasing in softening, attributable to their interactions with lipid headgroups. In contrast, [dmim][Cl], distinguished by its longer alkyl chain, enhances bilayer stiffness and rupture force, underscoring the critical role of hydrophobic interactions and alkyl chain penetration into the bilayer core. The findings highlight the dual influence of cations and anions on the mechano-elastic properties of lipid bilayers, providing insights into their mechanisms of action. This thesis also explores the cytotoxicity of ILs using MTT assays on breast cancer MDA MB-231 cells, identifying subtoxic concentrations suitable for biomembrane models doping studies. The results contribute to a broader understanding of IL-biomembrane interactions, offering implications for their application in biomedical and pharmaceutical fields, such as drug delivery systems. The research paves the way for the development of IL-based therapeutic strategies targeting cancer cell membranes and provides a foundation for further exploration of ILs in biophysical and biomedical contexts
Franco Cassano. Nota bio-bibliografica
La riflessione di Franco Cassano si apre all’insieme dell’esperienza umana: né il provvidenzialismo marxiano, né la logica di “misura” che si poneva a garanzia del pluriverso meridiano appaiono sufficienti di fronte ai venti di de-globalizzazione. Lo scatenamento della storia pone l’uomo moderno di fronte all’inconsistenza della propria autonomia. Il bene non arriva da sé: chi crede in un orizzonte di trasformazione non può limitarsi a enunciarlo o a praticarlo da par suo, ma deve sforzarsi continuamente di riconnetterlo alla situazione concreta – antropologica ed esistenziale – delle maggioranze silenziose. Il bene non è inscritto nel cuore degli uomini. È una costruzione artificiale e per molti versi contro natura, che richiede lotta, pedagogia, politica
Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity in cells
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) targeting PARP1 and PARP2 have revolutionized cancer therapy by selectively killing cancer cells with defective DNA repair. However, achieving PARP1 or PARP2-selective inhibitors is difficult due to structural homology. Selectivity profiling is typically done with purified proteins, but these lack the complexity of intracellular environments and could therefore be inaccurate. Here, we duplex PARP1 L713F-GFP and PARP2 L269A-mCherry cellular target engagement by accumulation of mutant (CeTEAM) drug biosensors to systematically characterize binding and cell cycle alterations of 27 PARPi. Our results reveal that most PARPi are equipotent for both PARPs, including the next-generation drug, senaparib. However, benzimidazole carboxamide (niraparib) derivatives demonstrated PARP1-selective tendencies, while phthalazinones (olaparib) favored PARP2. AZD5305, a reported PARP1-selective inhibitor with characteristics of both series, was the exception and appears ∼1600-fold more potent toward PARP1. In agreement with current understanding, we see that trapping-associated S/G2-phase transitions positively correlate with PARP1/2 binding potency, while some potent binders, such as veliparib, did not – likely reflecting their allosteric influence on DNA retention. We also assessed the effect of the PARP1/2 active site component, histone PARylation factor 1, on intracellular PARPi binding and see that its depletion elicits slight deviations in apparent binding potency, while contributing additively to trapping-like phenotypes. The PARP1/2 CeTEAM platform thus provides a structural roadmap for the development of selective PARPi and should facilitate the discovery of targeted therapies. Furthermore, our results highlight that multiplexing CeTEAM biosensors and layered genetic perturbations can systematically profile determinants of intracellular drug selectivity
Exploration of Bromodomain Proteins as Drug Targets for Niemann–Pick Type C Disease
Defects in lysosomal cholesterol handling provoke fatal disorders presenting neurovisceral symptoms with variable onset and life spans. A prime example is Niemann-Pick type C disease (NPCD), where cholesterol export from the endosomal-lysosomal system is impaired due to variants of either NPC intracellular cholesterol transporter 1 (NPC1) or NPC intracellular cholesterol transporter 2 (NPC2). Therapeutic options for NPCD are limited to palliative care and disease-modifying drugs, and there is a need for new treatments. Here, we explored bromodomain and extra-terminal domain (BET) proteins as new drug targets for NPCD using patient-derived skin fibroblasts. Treatment with JQ1, a prototype BET protein inhibitor, raised the level of NPC1 protein, diminished lysosomal expansion and cholesterol accumulation, and induced extracellular release of lysosomal components in a dose-, time-, and patient-dependent manner. Lastly, JQ1 enhanced and reduced cholesterol accumulation induced by pharmacologic inhibition of NPC1 and of histone deacetylase (HDAC) activity, respectively. Taken together, bromodomain proteins should be further explored as therapeutic drug targets for lysosomal diseases like NPCD, and as new components regulating lysosomal function and cholesterol metabolism
Il transito dei giovani ambasciatori e le spese effettuate dalla comunità civile
Il volume ripercorre attraverso documenti e immagini la missione effettuata da una ambasceria Giapponese in Italia nel 158
Fare system selection and line planning for new suburban rail lines considering the supply–demand interactions
For newly constructed suburban railway lines, the lack of historical passenger flow data presents a significant challenge in designing line plans and selecting an appropriate fare system. To address this issue, a least-squares procedure is employed to estimate both a gravity model and a polynomial model, which capture the interaction between passenger demand and supply factors for the existing railway network in the same region as the new lines, using geographic data, socioeconomic data, historical passenger flow, and train operation data. These models are then utilized to capture the interdependencies between demand and supply for the new suburban railway lines. An integrated line planning optimization framework is proposed that incorporates either the gravity or polynomial model for demand estimation to optimize line plan and fare system selection considering the impact of travel time and ticket costs on passenger demand. In this study, the estimated gravity and polynomial models express demand as a function of generalized travel time and ticket costs, these factors are closely tied to both line planning and fare system selection decisions. This enables the line planning optimization model to flexibly consider scenarios where newly constructed railway corridors implement different line-setting and different fare system configurations, while also evaluating the contribution of specific strategy attributes to demand generation and simultaneously addressing demand allocation. The proposed method has been tested using Shanghai's urban and suburban lines. Historical data from the entire Shanghai subway network were used to analyze the interdependencies between demand and supply, which were then applied to two new lines – the Shanghai Jiading–Minhang Line and the Airport Link Line – to assist decision-making regarding line setting and fare system selection. The computational results indicate that the accuracy of demand estimation has significantly improved by incorporating both supply-side and demand-side factors. Additionally, embedding these demand–supply interdependencies into the line planning optimization model has greatly enhanced the ability of train operation solutions to balance passenger demand with capacity supply
Geopolitical risks, critical materials and energy transition: Insights from wavelet analysis
This paper investigates how the prices of selected energy transition-related commodities respond to geopolitical risks, with particular attention to the suitability of a widely used geopolitical risk index in relation to the commodities included in the dataset. From a methodological perspective, the analysis is conducted via a wavelet-based method. The dataset includes natural gas, copper, palladium, and cobalt futures prices, whose time series cover a fourteen-year time span (2010-2024), while geopolitical risk is measured through the well known text-based geopolitical risk (GPR) index by Caldara and Iacoviello. The study is supported by an in-depth geopolitical discussion, analyzing events and dynamics relevant to the current international context. Our investigation shows different degrees of correlation between geopolitical risk and the above-mentioned commodities. From an overall perspective, commodities with a long-standing history of application tend to exhibit a more straightforward connection with geopolitical dynamics. In contrast, those that have recently gained prominence in the energy transition — especially newer entrants — show weaker and less consistent signals. In this respect, despite its widespread use in the literature, we infer that the GPR index has certain limitations when used to explain dynamics affecting rare and critical elements — particularly those sourced from geographical areas that are not regularly covered by mainstream media. The issue of the GPR index's adequacy in such contexts appears to be largely overlooked in current academic sources. Recognizing that the energy transition is driving a paradigm shift from a geostrategic standpoint requires a critical awareness when employing such indexes. At the same time, it calls for rethinking how risk indexes are designed, so that they better reflect geopolitical phenomena linked to the new centers of gravity emerging from the energy transition. The results are directed towards policymakers and regulators, who are called upon to govern the energy transition with a focus on the availability of critical materials in the coming decades
LA VALUTAZIONE DEL CLIMA SCOLASTICO E DELLE COMPETENZE SOCIO-EMOTIVE PER LA PROMOZIONE DEL BENESSERE DEGLI STUDENTI
In un contesto educativo in continua trasformazione, segnato da sfide complesse e da una crescente attenzione al benessere psico-sociale degli studenti, la valutazione del clima scolastico e delle competenze socio-emotive rappresenta una dimensione strategica per comprendere i processi educativi e progettare interventi orientati alla promozione del benessere scolastico. Il volume propone un modello integrato di analisi e valutazione, fondato su due costrutti interdipendenti – il clima scolastico e le competenze socio-emotive – il cui impatto sull’esperienza scolastica è ampiamente documentato dalla letteratura scientifica e dalle principali indagini internazionali (OCSE-PISA 2015, 2018, 2022; OCSE-SSES 2022). Vengono presentati due strumenti operativi validati per il contesto italiano: il Comprehensive School Climate Inventory e il Questionario per la Rilevazione dell’Atteggiamento Resiliente, utili per raccogliere dati significativi a supporto di pratiche valutative e progettuali nella scuola. Lo studio intreccia cornici teoriche, evidenze empiriche e prospettive applicative, offrendo indicazioni metodologiche per un uso formativo degli strumenti e per l’interpretazione dei dati con consapevolezza e alla luce delle specificità educative e culturali. Viene valorizzata la funzione degli strumenti valutativi come supporto alla lettura dei bisogni educativi e alla definizione di pratiche scolastiche orientate al benessere, alla resilienza e alla qualità delle relazioni. Il volume si rivolge a ricercatori, studiosi, dirigenti scolastici, docenti e professionisti dell’educazione impegnati nella promozione di contesti scolastici capaci di sostenere lo sviluppo integrale degli studenti in una prospettiva ecologica e inclusi