1,721,010 research outputs found
Deterministic and Stochastic Modeling of Human Papillomavirus Gene Regulatory Network
Full text linkIn this thesis a novel stochastic and deterministic mathematical model of Human papillomavirus (HPV) gene regulatory network was developed.
The novelty of this project is both on methodological and biological /clinical site. The former is in line with the current challenge in recent years to have a holistic view of the basics regulatory mechanisms interconnected to form a complex machinery, where complex patterns can arise, only form the interconnection of basics modules. In fact, HPV offers a case of study of great interest in molecular systems biology. It involves a number of relevant regulatory mechanisms (e.g. transcription, translation, promoter modulation, polyadenylation regulation, splicing,…) connected together to form a complex network, albeit its genome is relatively simple, thus suitable for an accurate deterministic and even stochastic modeling.
HPVs cause a series of diseases of the cutaneous and mucosal epithelium, ranging from minor lesions to precancerous cervical lesions and cervical cancer, which is considered one of the most common cancer in the women worldwide. Therefore, on the biological/clinical aspect the development of a mathematical model of HPV gene expression, is of great interest in order to dispose of an in silico simulator useful to achieve a better comprehension of the complex gene regulatory network, and capable to predict different scenarios from the first stages of viral infection up to a cervical cancer condition. As far as we know, there is no model of HPV gene regulation available in literature.
A new synthesis of the HPV molecular biology with especial regard to gather/infer from literature the parameters useful for designing a dynamical model, and to shed light in what is still lacking in the biological literature, was preformed.
The biological knowledge was translated into a stochastic model in terms of biochemical reactions. In particular, we modeled the HPV early and late promoters that account for the transcripts and proteins evolution during the entire viral life cycle. Even the post-transcriptional and post-translational modifications were modeled in order to properly capture the complex viral regulation known from literature.
As far as we know, it is the first time a stochastic model accounts for the complex post-transcriptional control, modeling the splicing and polyadenylation sites regulation, and connect this latter to the transcriptional control layer, mediated by the promoters activities, in order to explore complex patterns that can arise only from the interconnection of different control layers.
The Master Equation (ME) of the system was considered in order to predict and investigate its stochastic behavior. Because of the complex system structure it wasn't possible to solve the whole ME analytically, hence numerical exact simulations were performed by means of the Gillespie's algorithm. A quasi-equilibrium approximation of the ME was developed in order to get a deterministic approximation of the model.
The model structure together with the fixed parameters we have gathered/inferred from literature was able to fit a dataset consistent of the early promoter activity and to qualitatively reproduce the main dynamical behavior of two of the most important regulatory transcripts during viral late phase.
Different in silico experiments were designed to opportunely explore both the capability of the stochastic model to follows the deterministic predictions, when in fast fluctuations regimen, and to discover complex stochastic patterns, that can arise through the interconnection of the transcriptional and post-transcriptional control layers.
In general, both the stochastic and deterministic formulation of the model showed the capability to reproduce the HPV gene expression dynamics, during the entire viral life cycle, in good agreement with the current biological knowledge
Security Vulnerabilities and Countermeasures for Target Localization in Bio-NanoThings Communication Networks
No full textDDoS-Capable IoT Malwares: Comparative Analysis and Mirai Investigation
Full text linkThe Internet of Things (IoT) revolution has not only carried the astonishing promise to interconnect a whole generation of traditionally “dumb” devices, but also brought to the Internet the menace of billions of badly protected and easily hackable objects. Not surprisingly, this sudden flooding of fresh and insecure devices fueled older threats, such as Distributed Denial of Service (DDoS) attacks. In this paper, we first propose an updated and comprehensive taxonomy of DDoS attacks, together with a number of examples on how this classification maps to real-world attacks. Then, we outline the current situation of DDoS-enabled malwares in IoT networks, highlighting how recent data support our concerns about the growing in popularity of these malwares. Finally, we give a detailed analysis of the general framework and the operating principles of Mirai, the most disruptive DDoS-capable IoT malware seen so far
Physiologically based modelling of the antiplatelet effect of aspirin: A tool to characterize drug responsiveness and inform precision dosing.
Full text linkA computational approach involving mathematical modeling and in silico experiments was used to characterize the determinants of extent and duration of platelet cyclooxygenase (COX)-1 inhibition by aspirin and design precision dosing in patients with accelerated platelet turnover or reduced drug bioavailability. To this purpose, a recently developed physiologically-based pharmacokinetics (PK) and pharmacodynamics (PD) model of low-dose aspirin in regenerating platelets and megakaryocytes, was used to predict the main features and determinants of platelet COX-1 inhibition. The response to different aspirin regimens in healthy subjects and in pathological conditions associated with alterations in aspirin PK (i.e., severely obese subjects) or PD (i.e., essential thrombocytemya patients), were simulated. A model sensitivity analysis was performed to identify the main processes influencing COX-1 dynamics. In silico experiments and sensitivity analyses indicated a major role for megakaryocytes and platelet turnover in determining the extent and duration of COX-1 inhibition by once-daily, low-dose aspirin. They also showed the superiority of reducing the dosing interval vs increasing the once-daily dose in conditions of increased platelet turnover, while suggested specific dose adjustments in conditions of possible reduction in drug bioavailability. In conclusion, the consistency of our model-based findings with experimental data from studies in healthy subjects and patients with essential thrombocythemia supports the potential of our approach for describing the determinants of platelet inhibition by aspirin and informing precision dosing which may guide personalized antithrombotic therapy in different patient populations, especially in those under-represented in clinical trials or in those associated with poor feasibility
Microservices: Migration of a Mission Critical System
No full textAn increasing interest is growing around the idea of microservices and the promise of improving scalability when compared to monolithic systems. Several companies are evaluating pros and cons of a complex migration. In particular, financial institutions are positioned in a difficult situation due to the economic climate and the appearance of agile competitors that can navigate in a more flexible legal framework and started their business since day one with more agile architectures and without being bounded to outdated technological standard. In this paper, we present a real world case study in order to demonstrate how scalability is positively affected by re-implementing a monolithic architecture (MA) into a microservices architecture (MSA). The case study is based on the FX Core system, a mission critical system of Danske Bank, the largest bank in Denmark and one of the leading financial institutions in Northern Europe. The technical problem that has been addressed and solved in this paper is the identification of a repeatable migration process that can be used to convert a real world Monolithic architecture into a Microservices architecture in the specific setting of financial domain, typically characterized by legacy systems and batch-based processing on heterogeneous data sources
Analysis of DDoS-capable IoT malwares
Full text linkThe Internet of Things (IoT) revolution promises to make our lives easier by providing cheap and always connected smart embedded devices, which can interact on the Internet and create added values for human needs. But all that glitters is not gold. Indeed, the other side of the coin is that, from a security perspective, this IoT revolution represents a potential disaster. This plethora of IoT devices that flooded the market were very badly protected, thus an easy prey for several families of malwares that can enslave and incorporate them in very large botnets. This, eventually, brought back to the top Distributed Denial of Service (DDoS) attacks, making them more powerful and easier to achieve than ever. This paper aims at provide an up-to-date picture of DDoS attacks in the specific subject of the IoT, studying how these attacks work and considering the most common families in the IoT context, in terms of their nature and evolution through the years. It also explores the additional offensive capabilities that this arsenal of IoT malwares has available, to mine the security of Internet users and systems. We think that this up-to-date picture will be a valuable reference to the scientific community in order to take a first crucial step to tackle this urgent security issue
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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