A feasibility study on pairing a smartwatch and a mobile device through multi-modal gestures

Pairing is the process of establishing an association between two personal devices. Although such a process is intuitively very simple, achieving a straightforward and secure association is challenging due to several possible attacks and usability-related issues. Indeed, malicious attackers might want to spoof the communication between devices in order to gather sensitive information or harm them. Moreover, offering users simple and usable schemes which attain a high level of security remains a major issue. In addition, due to the great diversity of pairing scenarios and equipment, achieving a single, usable, secure association for all possible devices and use cases is simply not possible. In this thesis, we study the feasibility of a novel pairing scheme based on multi-modal gestures, namely, gestures involving drawing supported by accelerometer data. In particular, a user can pair a smart-watch on his wrist and a mobile device (e.g., a smart-phone) by simply drawing with a finger on the screen at the device. To this purpose, we developed mobile applications for smart-watch and smart-phone to sample and process sensed data in support of a secure commitment-based protocol. Furthermore, we performed experiments to verify whether encoded matching-movements have a clear similarity compared to non-matching movements. The results proved that it is feasible to implement such a scheme which also offers users a natural way to perform secure pairing. This innovative scheme may be adopted by a large number of mobile devices (e.g., smart-watches, smart-phones, tablets, etc.) in different scenarios

ONE-DIMENSIONAL HYDRODYNAMIC MODELS IN RIVER RESOURCE MANAGEMENT AND POLICY DESIGN

This thesis concludes a three-year doctoral program in hydraulic engineering. The research work focused on the development, testing and application of one-dimensional numerical models to river resources management and policy design issues, pointing out the key role numerical modeling can play to support river managers in the decision process where large-scale, eco-morphological river changes are supposed to occur. These latter may result in overwhelming environmental and socio-economic costs for the population and communities living along rivers, especially in developing countries: river morphological evolution cannot be neglected anymore when planning river resources use in large watersheds, and the need for tools capable of informing river managers is nowadays manifest. One-dimensional models, even though introducing simplifications in the description of hydrodynamics and sediment movement processes, do have some advantages. Provided modeling assumptions are correct, they are able to provide indicators that - despite not capturing all details - allow analyzing trends of morphological processes at reach-scale or basin scale. Moreover, they are time-saving and open the way to long-term analyses and implementation in optimization procedures. Models based on the shallow water equations for the liquid phase, together with the Exner equation for river bed evolution, have been used: two different numerical schemes for solving the governing equations have been implemented trying to improve model robustness and versatility. Even the simplest numerical models, built on simple numerical schemes, require a long case-specific model building work. Understanding of the river morphology evolution drivers and basic physical processes, hydrological and topographical data collection and pre-processing, adaptation of the model to the specific case study and specific features (e.g. control rule for the Isola Serafini diversion barrage, time-varying bifurcation for the Red River), choice of suitable closure equations (e.g. sediment transport formula), are all essential steps that influence reliability of results and claim the same carefulness as the development of the numerical model itself. Details are given about the model building process for each case study. We analyzed three different case studies of river system management in which numerical model simulations give a relevant contribution to the decision-making process. - River Po (Italy), in its lower course, has undergone a severe bed lowering process during second half of the 20th century. The Isola Serafini hydropower plant, located on Po river, operating since 1962, is served by a 330 m wide barrage that still affects the hydrological regime and sediment supply downstream. Alternative operating rules for the barrage, over a time horizon of ten years, have been analyzed by the means of a one-dimensional hydro-morphological numerical model. A multi-objective optimization framework was implemented, to assess the effects of the operating rules on hydropower revenue and river bed incision. We adopted a surrogate modeling technique (Global Response Surfaces in the Learning and Planning procedure) to embed the hydro-morphological model in the optimization procedure in a multidisciplinary approach. The obtained results are encouraging and show that with a moderate loss in hydropower revenue, the decrease in river bed degradation can be remarkable. - The Red River (Song Hong) in northern VietNam has experienced severe river bed degradation along its lower course as well, but over a shorter period (last 15 years). The continued decrease of the water levels in the dry season aggravated water scarcity for agriculture. These outcomes can be attributed to strong instream sediment mining, major upstream impoundments, climatic and land use changes. The IMRR (Integrated and sustainable water Management of Red-Thai Binh Rivers System in changing climate) project, run by the Politecnico di Milano university with several Vietnamese agencies and authorities under the supervision of the Italian Ministry of Foreign Affairs, has faced several challenges inherent to water resources use in the Red River basin; the main river morphological evolution aspects of the last decades have been thoroughly analyzed and a finite-volume numerical model of the lower course of Red River has been set up and tested. The model has been used to evaluate the sensitivity of the river stretch to discharge modulation operated by upstream reservoirs, and to estimate instream sand mining rates to draw up some prediction scenarios. We showed that sediment mining rates, as expected, could be much larger than licensed amounts; this accelerates incision in the first reach and reverses the natural restoration trend in the following reaches, aggravating water level lowering. The flow control operated by reservoirs, conversely, appears to affect much less the morphological processes in the studied reach. - In January 2014, a serious flooding event (due to a levee breach) occurred in the Modena Province (Italy) along Secchia River. Concerns have increased about the role of vegetation in Secchia river channel during big floods. A detailed characterization of riparian vegetation features has then been produced by the Po River Interregional Agency (AIPo) to point out critical issues about current vegetation pattern along Secchia river banks and possibly plan a maintenance - remediation strategy. This characterization report constitutes a good basis for a hydrodynamic modelling work; a 1D finite-volume model, accounting for the influence of different vegetation patterns and densities on flow resistance has been applied to a 60 km long stretch of Secchia river. The agreement between simulation results and gauged data on a real flood event is encouraging and opens the way to the use of the model for evaluating the effectiveness of future vegetation management plans

Ordering of Ge quantum dots on silicon surfaces via bottom-up and top-down approaches

The nanoscale ordering of inorganic semiconductor quantum dots (QDs) is crucial to obtain reliable structures for novel nanotechnological applications such as nanomemories, nanolasers and nanoelectronic devices. We have directly grown Ge QDs by physical vapour deposition (PVD) on Si(111), Si(100) and some of its vicinal surfaces and studied innovative bottom up techniques to order such nanostructures. Specifically, we harnessed naturally occurring instabilities due to reconstruction and intrinsic anisotropic diffusion in Si bare surfaces, such as step bunching and natural steps occurring in silicon vicinal surfaces, to order the QDs both in one dimension and in the plane. We have also shown the use of controlled quantities of surfactants, like Sb, dramatically improves the desired ordering. Moreover, we have assisted these self-assembling processes using top-down approaches like Focused Ion Beam (FIB) milling and STM nanoindentation to control the nucleation sites and the density of the Ge QDs. Real-time study of growth and self-assembly has been accomplished using Scanning Tunneling Microscopy imaging in UHV. An explanation of the occurring processes is given, and a software routine is used to quantify the ordering of the QDs both in pre-patterned and bare surfaces. Applications, mainly in the field of Nanocrystal Nonvolatile Memories, are discussed

Accounting for river morphology in the management of red river (vietnam): a numerical modeling approach

During last 15 years, the Red River in northern VietNam has experienced severe river bed degradation along its lower course. The continued decrease of the minimum water levels aggravated water scarcity for agriculture. These outcomes can be attributed to strong in stream sediment mining, major upstream impoundments, climatic and land use changes. The aim of this work is to provide a valuable tool to assess the effects of different reservoir water releases and sediment mining policies on river reach morphology. A 1D mobile bed finite volume numerical model has been set up and preliminary results on the recent 2000-2009 period are presented and discussed. The model features facilitate its integration in optimization algorithms devoted to water management strategies

DNA base editing corrects common Hemophilia A mutations and restores factor VIII expression in vitro and ex-vivo models

Background: Replacement and non-replacement therapies effectively control bleedings in Hemophilia A (HA) but imply lifelong interventions. The authorized gene addition therapy could provide a cure but still poses questions on durability. F8 gene correction would definitively restore factor VIII (FVIII) production, as shown in animal models through nucleases mediating homologous recombination (HR). However, low efficiency and potential off-target double-strand break (DSB) still limit HR translatability. Objectives: To correct common model single point mutations leading to severe HA through the recently developed DSB/HR-independent base (BE) and prime (PE) editing approaches. Methods: Screening for efficacy of BE/PE systems in HEK293T transiently expressing FVIII variants and validation at DNA (sequencing) and protein (ELISA; aPTT) level in stable clones. Evaluation of rescue in engineered blood outgrowth endothelial cells (BOEC) by lentiviral-mediated delivery of BE. Results and conclusions: Transient assays identified the best-performing BE/PE systems for each variant, with the highest rescue of FVIII expression (up to 25% of rFVIIIwt) for the p.R2166* and p.R2228Q mutations. In stable clones we demonstrated that the mutation reversion on DNA (∼24%) was consistent with the rescue of FVIII secretion and activity 20-30%). The lentiviral-mediated delivery of the selected BE systems was attempted in engineered BOEC harboring the p.R2166* and p.R2228Q variants, which led to an appreciable and dose-dependent rescue of secreted functional FVIII. Overall data provide the first proof-of-concept for effective BE/PE-mediated correction of HA-causing mutations, which encourage studies in mouse models to develop a personalized cure for large cohorts of patients though a single intervention

DOES THE SITTING POSITION INFLUENCE CLAY TARGET SHOOTING PERFORMANCE IN ATHLETES WITH A MOTOR IMPAIRMENT?

Olympic trap clay target shooting (CTS) is currently performed by motor impaired individuals (MII), but not yet included in the International Paralympic Committee endorsement. This study aimed at supporting the development of a classification model that divides athletes competing in standing and sitting postures. Two groups of 5 standing and 5 sitting MII athletes were recruited for an instrumented CTS task execution. During competition, sitting athletes showed a lower rate of success with respect to the standing ones only for targets requiring wider ranges of motion, possibly due to fatigue. Their predominant use of upper body movements implies an adapted technique to reach a good performance, testified by a smoother movement, a lower peak accelerations at the gun tip, a smaller range for all absolute and relative rotations, and a different muscle activity

C6orf10 low-frequency and rare variants in italian multiple sclerosis patients

In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value <= 5 x 10(-6)). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) <= 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs 16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 x 10(-7) and p < 1 x 10(-20)). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value ≤ 5 × 10−6). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 × 10−7 and p < 1 × 10−20). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3′ region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS

An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects

A significant proportion of disease-causing mutations affect precursor-mRNA splicing, inducing skipping of the exon from the mature transcript. Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA). In minigene expression systems, loading of U1 snRNA by complementarity to the normal or mutated donor splice sites (5′ss) corrected the exon skipping caused by mutations at the polypyrimidine tract of the acceptor splice site, at the consensus 5′ss or at exonic regulatory elements. To improve specificity and reduce potential off-target effects, we developed U1 snRNA variants targeting non-conserved intronic sequences downstream of the 5′ss. For each gene system, we identified an exon-specific U1 snRNA (ExSpeU1) able to rescue splicing impaired by the different types of mutations. Through splicing-competent cDNA constructs, we demonstrated that the ExSpeU1-mediated splicing correction of several F9 mutations results in complete restoration of secreted functional factor IX levels. Furthermore, two ExSpeU1s for SMA improved SMN exon 7 splicing in the chromosomal context of normal cells. We propose ExSpeU1s as a novel therapeutic strategy to correct, in several human disorders, different types of splicing mutations associated with defective exon definition