Sviluppo di un front-end di simulazione per applicazioni aggregate nel framework Scafi

La tesi è articolata in sei capitoli: nel primo vengono introdotti gli studi pregressi realizzati durante il periodo di tirocinio svolto presso l'Università di Bologna, utili a comprendere l'insieme di scelte effettuate nelle altre fasi dello studio. Nel secondo capitolo viene descritta la fase di analisi del modello da realizzare, completa di elenco dei requisiti che il front-end deve rispettare, in questa fase in modo particolare, c'è stato uno scambio di informazioni costante con il prof. Mirko Viroli e il dott. Roberto Casadei nei panni dei 'committenti' nel progetto. Nel terzo capitolo si descrive la fase di progettazione architetturale, fornendo informazioni su come il software realizza quanto richiesto in fase di analisi in termini di architettura. Si descrive, quindi, la struttura generale del front-end e si spiega il perché delle varie scelte presenti in questa fase. Nel quarto capitolo vengono descritte, invece, quelle che sono le scelte di design dettagliato, in particolare si descrive com'è possibile interfacciare il front-end con il framework \class{ScaFi} e come avviare e descrivere una simulazione aggregata. Nel quinto capitolo vengono mostrate le scelte implementative per la realizzazione del software e vengono mostrati alcuni screenshot con i risultati ottenuti e, infine, nel sesto si offre una panoramica di quello che è il risultato finale mostrando la struttura dell'interfaccia grafica corredato di analisi delle performance estratte da alcune delle possibili simulazioni eseguibili sul front-en

Spontaneous internal desynchronization of locomotor activity and body temperature rhythms from plasma melatonin rhythm in rats exposed to constant dim light

BACKGROUND: We have recently reported that spontaneous internal desynchronization between the locomotor activity rhythm and the melatonin rhythm may occur in rats (30% of tested animals) when they are maintained in constant dim red light (LL(dim)) for 60 days. Previous work has also shown that melatonin plays an important role in the modulation of the circadian rhythms of running wheel activity (R(w)) and body temperature (T(b)). The aim of the present study was to investigate the effect that desynchronization of the melatonin rhythm may have on the coupling and expression of circadian rhythms in R(w )and T(b). METHODS: Rats were maintained in a temperature controlled (23–24°C) ventilated lightproof room under LL(dim )(red dim light 1 μW/cm(2 )[5 Lux], lower wavelength cutoff at 640 nm). Animals were individually housed in cages equipped with a running wheel and a magnetic sensor system to detect wheel rotation; T(b )was monitored by telemetry. T(b )and R(w )data were recorded in 5-min bins and saved on disk. For each animal, we determined the mesor and the amplitude of the R(w )and T(b )rhythm using waveform analysis on 7-day segments of the data. After sixty days of LL(dim )exposure, blood samples (80–100 μM) were collected every 4 hours over a 24-hrs period from the tail artery, and serum melatonin levels were measured by radioimmunoassay. RESULTS: Twenty-one animals showed clear circadian rhythms R(w )and T(b), whereas one animal was arrhythmic. R(w )and T(b )rhythms were always strictly associated and we did not observe desynchronization between these two rhythms. Plasma melatonin levels showed marked variations among individuals in the peak levels and in the night-to-day ratio. In six rats, the night-to-day ratio was less than 2, whereas in the rat that showed arrhythmicity in R(w )and T(b )melatonin levels were high and rhythmic with a large night-to-day ratio. In seven animals, serum melatonin levels peaked during the subjective day (from CT0 to CT8), thus suggesting that in these animals the circadian rhythm of serum melatonin desynchronized from the circadian rhythms of R(w )and T(b). No significant correlation was observed between the amplitude (or the levels) of the melatonin profile and the amplitude and mesor of the R(w )and T(b )rhythms. CONCLUSION: Our data indicate that the free-running periods (τ) and the amplitude of R(w )and T(b )were not different between desynchronized and non-desynchronized rats, thus suggesting that the circadian rhythm of serum melatonin plays a marginal role in the regulation of the R(w )and T(b )rhythms. The present study also supports the notion that in the rat the circadian rhythms of locomotor activity and body temperature are controlled by a single circadian pacemaker

Dynamic Decentralization Domains for the Internet of Things

The Internet of Things (IoT) and edge computing are fostering a future of ecosystems hosting complex decentralized computations that are deeply integrated with our very dynamic environments. Digitalized buildings, communities of people, and cities will be the next-generation "hardware and platform,"counting myriads of interconnected devices, on top of which intrinsically distributed computational processes will run and self-organize. They will spontaneously spawn, diffuse to pertinent logical/physical regions, cooperate and compete, opportunistically summon required resources, collect and analyze data, compute results, trigger distributed actions, and eventually decay. What would a programming model for such ecosystems look like? Based on research findings on self-adaptive/self-organizing systems, this article proposes design abstractions based on "dynamic decentralization domains": regions of space opportunistically formed to support situated recognition and action. We embody the approach into a Scala application program interface (API) enacting distributed execution and show its applicability in a case study of environmental monitoring

ScaFi: A Scala DSL and Toolkit for Aggregate Programming

Supported by current socio-scientific trends, programming the global behaviour of whole computational collectives makes for great opportunities, but also significant challenges. Recently, aggregate computing has emerged as a prominent paradigm for so-called collective adaptive systems programming. To shorten the gap between such research endeavours and mainstream software development and engineering, we present ScaFi, a Scala toolkit providing an internal domain-specific language, libraries, a simulation environment, and runtime support for practical aggregate computing systems development

Addressing Collective Computations Efficiency: Towards a Platform-level Reinforcement Learning Approach

Aggregate Computing is a macro-level approach for programming collective intelligence and self-organisation in distributed systems. In this paradigm, system behaviour unfolds as a combination of a system-wide program, functionally manipulating distributed data structures called computational fields, and a distributed protocol where devices work at asynchronous rounds comprising sense-compute-interact steps. Interestingly, there exists a large amount of flexibility in how aggregate systems could actually execute while preserving the desired functionality. The ideal place for making choices about execution is the aggregate computing platform (or middleware), which can be engineered with the goal of promoting efficiency and other non-functional goals. In this work, we explore the possibility of applying Reinforcement Learning at the platform level in order to optimise aspects of a collective computation while achieving coherent functional goals. This idea is substantiated through synthetic experiments of data propagation and collection, where we show how Q-Learning could reduce the power consumption of aggregate computations

Intracellular targets of RGDS peptide in melanoma cells

<p>Abstract</p> <p>Background</p> <p>RGD-motif acts as a specific integrins-ligand and regulates a variety of cell-functions via extracellular action affecting cell-adhesion properties. However, increasing evidence identifies additional RGDS-functions at intracellular level. Previous reports show RGDS-internalization in endothelial cells, cardiomyocytes and lymphocytes, indicating intracellular targets such as caspase-8 and caspase-9, and suggest RGDS specific activity at cytoplasmic level. Given the role RGDS-peptides play in controlling proliferation and apoptosis in several cell types, investigating intracellular targets of RGDS in melanoma cells may un-reveal novel molecular targets and key pathways, potentially useful for a more effective approach to melanoma treatment.</p> <p>Results</p> <p>In the present study we show for the first time that RGDS-peptide is internalized in melanoma cells in a time-dependent way and exerts strong anti-proliferative and pro-apoptotic effects independently from its extracellular anti-adhesive action. RGES control-peptide did not show biological effects, as expected; nevertheless it is internalized, although with slower kinetics. Survivin, a known cell-cycle and survival-regulator is highly expressed in melanoma cells. Co-immunoprecipitation assays in cell lysates and overlay assays with the purified proteins showed that RGDS interacts with survivin, as well as with procaspase-3, -8 and -9. RGDS-peptide binding to survivin was found to be specific, at high affinity (Kd 27.5 μM) and located at the survivin C-terminus. RGDS-survivin interaction appeared to play a key role, since RGDS lost its anti-mitogenic effect in survivin-deprived cells with a specific siRNA.</p> <p>Conclusions</p> <p>RGDS inhibits melanoma growth with an adhesion-independent mechanism; it is internalized in melanoma cells and specifically interacts with survivin. The present data may indicate a novel role of RGDS-containing peptides physiologically released from the extracellular matrix and may suggest a possible novel anti-proliferation strategy in melanoma.</p

RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells

AbstractPeptides containing the Arg-Gly-Asp (RGD) motif inhibit cell adhesion and exhibit a variety of other biologic effects including anticoagulant and antimetastatic activities. The aim of the present study was to examine the anchorage-independent effects of an RGD-containing peptide, Arg-Gly-Asp-Ser (RGDS), on human umbilical vein endothelial cells (HUVECs). Assays were performed on HUVECs seeded onto collagen IV; under these experimental conditions RGDS did not exert antiadhesive effects but significantly reduced FGF-2-dependent chemotaxis after 4 hours of treatment and reduced proliferation after 24 hours of treatment. Experiments carried out with caspase-specific inhibitors indicated that the observed antichemotactic effects required caspase 8 and caspase 9 activation. RGDS activated both caspase 8 and caspase 9 after 4 hours of treatment and caspase 3 after 24 hours of treatment, and markedly enhanced HUVEC apoptosis by transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)/Hoechst staining and fluorescence-activated cell sorting (FACS) analysis. Finally, confocal microscopy showed that RGDS localizes in the cytoplasm of live HUVECs within 4 hours and in vitro experiments showed that RGDS directly interacts with recombinant caspases 8 and 9 in a specific way. In summary, these results indicate that RGDS directly binds and activates caspases 8 and 9, inhibits chemotaxis, and induces apoptosis of HUVECs with a mechanism independent from its antiadhesive effect

Cost-effectiveness analysis of universal human papillomavirus vaccination using a dynamic Bayesian methodology: The BEST II study

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Dynamic decentralization domains for the Internet of Things - Simulation Repository

The Internet of Things and edge computing are fostering a future of ecosystems hosting complex decentralized computations, deeply integrated with our very dynamic environments. Digitalized buildings, communities of people, and cities will be the next-generation “hardware and platform”, counting myriads of interconnected devices, on top of which intrinsically-distributed computational processes will run and self-organize. They will spontaneously spawn, diffuse to pertinent logical/physical regions, cooperate and compete, opportunistically summon required resources, collect and analyze data, compute results, trigger distributed actions, and eventually decade. How would a programming model for such ecosystems look like? Based on research findings on self-adaptive/self-organizing systems, this paper proposes design abstractions based on “dynamic decentralization domains”: regions of space opportunistically formed to support situated recognition and action. We embody the approach into a Scala API to enact distributed execution on a network of devices and show its applicability in a case study of environmental monitoring