Polyamine–Drug Conjugates: Do They Boost Drug Activity?

Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments

The assessment of hemineglect syndrome with cancellation tasks. A comparison between the bells test and the Apples test

Unilateral spatial neglect (USN) is a frequent consequence of acquired brain injury, especially following right hemisphere damage. Traditionally, unilateral spatial neglect is assessed with cancellation tests such as the Bells test. Recently, a new cancellation test, the Apples test, has been proposed. The present study aims at comparing the accuracy of these two tests in detecting hemispatial neglect, on a sample of 56 right hemisphere stroke patients with a diagnosis of USN. In order to evaluate the agreement between the Apples and Bells tests, Cohen's kappa and McNemar's test were used to assess differences between the two methods of evaluation. Poor agreement and statistically significant differences emerged between the Apples and Bells tests. Overall, the Apples test was significantly more sensitive than the Bells test in detecting USN. Based on these results, the use of the Apples test for peripersonal neglect assessment is therefore highly recommende

Covalent stabilization of 2D self-assembled nanostructures on surfaces

The rise of graphene has attracted great interest in low-dimensional materials (0D, 1D and 2D). A joint effort among the different branches of science (chemistry, physics, materials science and related areas) is directed towards the production of new intriguing materials with tuneable graphene-like properties. Promising is the direct synthesis of organic nanostructures on metal surfaces under ultrahigh-vacuum conditions (UHV). Perfect tuning of the reaction conditions, high control of the surface symmetry and of its corrugation, a rich variety of substrate materials are only some of the advantage that UHV may offer. Although several reactions have been tested, it seems clear that to achieve ordered covalent monolayers more complex approaches are needed. In this thesis, the on-surface polymerization of covalent nanostructures has been studied for different coupling reactions, substrate materials and reaction conditions. Scanning tunneling microscopy and X-ray photoelectron spectroscopy are used for the characterization, allowing complementary analysis of molecular structures and chemical states. In particular, thermally activated reactions were used to gradually polymerize the 4,4”-dibromo-terphenyl precursor into poly-paraphenylene wires, through an Ullmann-like reaction scheme on Au(111), and then into graphene nanoribbons, after activation of the C-H bonds. A fine balance between the catalytic activity of the surface, molecular mobility and favourable molecular organization allowed us to get extended and ordered covalent structures. Taking advantage of this synthetic pathway, three different mono-dimensional polymers were obtained, namely poly-paraphenylene and two pyridinic derivatives, with gradually increased nitrogen content. Macroscopically anisotropic samples have been prepared by taking advantage of the vicinal surface templating effect. Using angle resolved photoemission spectroscopy, we reveal that the electronic structure of doped polymers is monotonically downshifted with respect to the metal Fermi level as the pyridine substitution is increased within the molecular scaffold. Finally, the photochemical activation of different functional groups has been explored. These studies represents a step forward in the application of organic photochemistry to on-surface synthesis, which is currently limited to the use of diacetylene groups, and it opens up new opportunities for using several organic functional groups as photoactive centres for the synthesis of covalent organic frameworks

Are There Any Parameters Missing in the Mathematical Models Applied in the Process of Spreading COVID-19?

On 11 March 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). As of 12.44 GMT on 15 January 2021, it has produced 93,640,296 cases and 2,004,984 deaths. The use of mathematical modelling was applied in Italy, Spain, and UK to help in the prediction of this pandemic. We used equations from general and reduced logistic models to describe the epidemic development phenomenon and the trend over time. We extracted this information from the Italian Ministry of Health, the Spanish Ministry of Health, Consumer Affairs, and Social Welfare, and the UK Statistics Authority from 3 February to 30 April 2020. We estimated that, from the seriousness of the phenomenon, the consequent pathology, and the lethal outcomes, the COVID-19 trend relate to the same classic laws that govern epidemics and their evolution. The curve d(t) helps to obtain information on the duration of the epidemic phenomenon, as its evolution is related to the efficiency and timeliness of the system, control, diagnosis, and treatment. In fact, the analysis of this curve, after acquiring the data of the first three weeks, also favors the advantage to formulate forecast hypotheses on the progress of the epidemic

NeutRAN: An Open RAN Neutral Host Architecture for Zero-Touch RAN and Spectrum Sharing

Obtaining access to exclusive spectrum, cell sites, Radio Access Network (RAN) equipment, and edge infrastructure imposes major capital expenses to mobile network operators. A neutral host infrastructure, by which a third-party company provides RAN services to mobile operators through network virtualization and slicing techniques, is seen as a promising solution to decrease these costs. Currently, however, neutral host providers lack automated and virtualized pipelines for onboarding new tenants and to provide elastic and on-demand allocation of resources matching operators' requirements. To address this gap, this paper presents NeutRAN, a zero-touch framework based on the O-RAN architecture to support applications on neutral hosts and automatic operator onboarding. NeutRAN builds upon two key components: (i) an optimization engine to guarantee coverage and to meet quality of service requirements while accounting for the limited amount of shared spectrum and RAN nodes, and (ii) a fully virtualized and automated infrastructure that converts the output of the optimization engine into deployable micro-services to be executed at RAN nodes and cell sites. NeutRAN was prototyped on an OpenShift cluster and on a programmable testbed with 4 base stations and 10 users from 3 different tenants. We evaluate its benefits, comparing it to a traditional license-based RAN where each tenant has dedicated physical and spectrum resources. We show that NeutRAN can deploy a fully operational neutral host-based cellular network in around 10 seconds. Experimental results show that it increases the cumulative network throughput by 2.18x and the per-user average throughput by 1.73x in networks with shared spectrum blocks of 30 MHz. NeutRAN provides a 1.77x cumulative throughput gain even when it can only operate on a shared spectrum block of 10 MHz (one third of the spectrum used in license-based RANs).Comment: 13 pages, 11 figures, 1 table. IEEE Transactions on Mobile Computing, August 202

Understanding O-RAN: Architecture, Interfaces, Algorithms, Security, and Research Challenges

The Open Radio Access Network (RAN) and its embodiment through the O-RAN Alliance specifications are poised to revolutionize the telecom ecosystem. O-RAN promotes virtualized RANs where disaggregated components are connected via open interfaces and optimized by intelligent controllers. The result is a new paradigm for the RAN design, deployment, and operations: O-RAN networks can be built with multi-vendor, interoperable components, and can be programmatically optimized through a centralized abstraction layer and data-driven closed-loop control. Therefore, understanding O-RAN, its architecture, its interfaces, and workflows is key for researchers and practitioners in the wireless community. In this article, we present the first detailed tutorial on O-RAN. We also discuss the main research challenges and review early research results. We provide a deep dive of the O-RAN specifications, describing its architecture, design principles, and the O-RAN interfaces. We then describe how the O-RAN RAN Intelligent Controllers (RICs) can be used to effectively control and manage 3GPP-defined RANs. Based on this, we discuss innovations and challenges of O-RAN networks, including the Artificial Intelligence (AI) and Machine Learning (ML) workflows that the architecture and interfaces enable, security and standardization issues. Finally, we review experimental research platforms that can be used to design and test O-RAN networks, along with recent research results, and we outline future directions for O-RAN development.Comment: 33 pages, 16 figures, 3 tables. Submitted for publication to the IEE

Wake-up radio-based data forwarding for green wireless networks

This paper presents G-WHARP, for Green Wake-up and HARvesting-based energy-Predictive forwarding, a wake-up radio-based forwarding strategy for wireless networks equipped with energy harvesting capabilities (green wireless networks). Following a learning-based approach, G-WHARP blends energy harvesting and wake-up radio technology to maximize energy efficiency and obtain superior network performance. Nodes autonomously decide on their forwarding availability based on a Markov Decision Process (MDP) that takes into account a variety of energy-related aspects, including the currently available energy and that harvestable in the foreseeable future. Solution of the MDP is provided by a computationally light heuristic based on a simple threshold policy, thus obtaining further computational energy savings. The performance of G-WHARP is evaluated via GreenCastalia simulations, where we accurately model wake-up radios, harvestable energy, and the computational power needed to solve the MDP. Key network and system parameters are varied, including the source of harvestable energy, the network density, wake-up radio data rate and data traffic. We also compare the performance of G-WHARP to that of two state-of-the-art data forwarding strategies, namely GreenRoutes and CTP-WUR. Results show that G-WHARP limits energy expenditures while achieving low end-to-end latency and high packet delivery ratio. Particularly, it consumes up to 34% and 59% less energy than CTP-WUR and GreenRoutes, respectively

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

open6noThis work was supported by the University of Pavia [to MA, grant number BSR1744747; 2017] and the Italian Ministry of University and Research [to MA, FFABR2017]. The University of Bologna is acknowledged by MR [Grants from RFO].Age-related macular degeneration (AMD) is a common disease with a multifactorial aetiology, still lacking effective and curative therapies. Among the early events triggering AMD is the deterioration of the retinal pigment epithelium (RPE), whose fundamental functions assure good health of the retina. RPE is physiologically exposed to high levels of oxidative stress during its lifespan; thus, the integrity and well-functioning of its antioxidant systems are crucial to maintain RPE homeostasis. Among these defensive systems, the Nrf2-pathway plays a primary role. Literature evidence suggests that, in aged and especially in AMD RPE, there is an imbalance between the increased pro-oxidant stress, and the impaired endogenous detoxifying systems, finally reverberating on RPE functions and survival. In this in vitro study on wild type (WT) and Nrf2-silenced (siNrf2) ARPE-19 cells exposed to various AMD-related noxae (H2O2, 4-HNE, MG132 + Bafilomycin), we show that the Nrf2-pathway activation is a physiological protective stress response, leading downstream to an up-regulation of the Nrf2-targets HO1 and p62, and that a Nrf2 impairment predisposes the cells to a higher vulnerability to stress. In search of new pharmacologically active compounds potentially useful for AMD, four nature-inspired hybrids (NIH) were individually characterized as Nrf2 activators, and their pharmacological activity was investigated in ARPE-19 cells. The Nrf2 activator dimethyl-fumarate (DMF; 10 μM) was used as a positive control. Three out of the four tested NIH (5 μM) display both direct and indirect antioxidant properties, in addition to cytoprotective effects in ARPE-19 cells under pro-oxidant stimuli. The observed pro-survival effects require the presence of Nrf2, with the exception of the lead compound NIH1, able to exert a still significant, albeit lower, protection even in siNrf2 cells, supporting the concept of the existence of both Nrf2-dependent and independent pathways mediating pro-survival effects. In conclusion, by using some pharmacological tools as well as a reference compound, we dissected the role of the Nrf2-pathway in ARPE-19 stress response, suggesting that the Nrf2 induction represents an efficient defensive strategy to prevent the stress-induced damage.openCatanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M.Catanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M

Bioethics, a transversal theme for secondary education, a study in teachers

This paper describes the data provided by 40 secondary education teachers on their knowledge and teaching in bioethics issues. The textbook, debate and research in small groups are the usual tools. Their training needs and the most appropriate methodology for teaching are discussed. Human health, biotechnology and new topics, such as animal abuse, are the most commented among students, without appreciating gender differences. Bioethics can be considered as a transversal one that encourages interdisciplinary work and the acquisition of skills.En este trabajo se describen los datos aportados por 40 profesores de Educación Secundaria sobre su conocimiento y docencia en temas de bioética. El libro de texto, el debate y los trabajos de investigación en grupos reducidos son las herramientas habituales. Se comentan sus necesidades de formación y la metodología más adecuada para la enseñanza. La salud humana, la biotecnología y nuevos temas, como el maltrato animal, son los más comentadas entre los estudiantes, sin apreciarse diferencias de género. La bioética puede plantearse como una transversal que fomente el trabajo interdisciplinar y la adquisición de las competencias