To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).
Next-generation targeted sequencing was used ...to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression.
First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio HR = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression.
These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
The purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).
...Next-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial-Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.
The opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio HR 1.36; P = 2.01 ∗ 10-3) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue -18β in the signal peptide and β57 in the β-chain to form six motifs. DQ*VA was associated with faster (HR 1.49; P = 6.36 ∗ 10-4) and DQ*AD with slower (HR 0.64; P = 0.020) progression to diabetes onset. VA/VA, representing DQA1*03:01-B1*03:02 (DQ8/8), had a greater HR of 1.98 (P = 2.80 ∗ 10-3). The DQ*VA motif was associated with both islet cell antibodies (P = 0.023) and insulin autoantibodies (IAAs) (P = 3.34 ∗ 10-3), while the DQ*AD motif was associated with a decreased IAA frequency (P = 0.015). Subjects with DQ*VA and DQ*AD experienced, respectively, increasing and decreasing trends of HbA1c levels throughout the follow-up.
HLA-DQ structural motifs appear to modulate progression from islet autoimmunity to diabetes among at-risk relatives with islet autoantibodies. Residue -18β within the signal peptide may be related to levels of protein synthesis and β57 to stability of the peptide-DQab trimolecular complex.
The concept of smartness is an essential topic that was only recently extended to rural areas. Although smartness is already incorporated strongly into numerous urban environments, differences ...between cities and villages prevent direct transfer of the methods and tools used for the smart transformation. To increase the awareness of newly developed or appropriately adapted tools and methods, their incorporation into a uniform platform is advisable. The paper presents the functional requirements and architectural backbone of a Digital Platform, currently being developed within the SmartVillages Project, Smart Digital Transformation of Villages in the Alpine Space. Key functionalities of the developed Digital Platform are (1) Self-assessment, allowing evaluation of smartness according to the different dimensions, (2) input and review of Best Practices regarding smart transformations, (3) Matchmaking, based on the results of self assessment, and (4) collaboration between involved parties. Functionalities are meant to be used by different village representatives, wherein the main purpose of the Digital Platform is to facilitate activities that could improve the smartness level of interested rural areas.
In recent years, the issue of vehicle road sharing has attracted growing attention from both researchers and operators, as a potential instrument to improve the sustainability of urban mobility or ...transport systems. Beside the general concept, different operational models, managerial and technological solutions have been developed, leading to a high diversification of possible vehicle sharing configurations. This heterogeneity entails a considerable complexity of the service design phase, though few academic contributions tackled this specific problem and most of the papers focused on the dynamics of adoption and use of the service itself. To fill such a gap, this paper aims to present the approach followed in the design phase of an electric vehicle sharing service for the city of Milano. The methodology adopted in this work is based on the idea that a vehicle sharing service needs to be configured to answer to specific mobility needs coherently with the characteristics of target customers. To explain this idea the methodology was articulated into four steps, which are reported in detail in this study: (i) mapping of mobility profiles and service performances, (ii) competitive analysis, (iii) development of the service configurations and (iv) development of the evaluation model.
Vehicle sharing is one of the possible answers to the increasing demand of sustainable way of transport. However, the traditional management models of sharing services are not flexible enough to be a ...real answer to current and future mobility needs. Green Move, an ongoing project financed by Regione Lombardia that involves eight different research centers of Politecnico di Milano, has the objective to design and test a vehicle-sharing system, with different categories of electric vehicles. The service will have the following characteristics: multi-ownership, allowing single users, private companies, and associations to join the service both using vehicles provided by the service itself and sharing their personal electric car or fleet, this represents an application of a peer2peer approach in the field of sustainable mobility; the Green e-Box, a device that will be the bridge between user, vehicle and control center, potentially compatible with any vehicle; key-less-mobility, meaning that personal smartphones will be the accesskey to the Green Move fleet, avoiding the use of smart-cards or physical keys. The design of a full scale service for the city of Milano will be carried out by a multi-criteria assessment of a wide number of possible alternative options in order to identify the most feasible and effective one. Indicators will be identified to measure the performance on relevant dimensions (i.e. economic and financial sustainability, social benefits, environmental effects). A trial to test the operating modes and the service efficiency will be carried out with electric vehicles and docking stations in a specific area of Milan, establishing a connection with the present traditional electric car sharing service owned by the Region. The performance of the service in term of accessibility and usability will be measured with a specific monitoring system. The paper aims to give a general overview of the project and a focus on the methodology in use for the full scale service design.
Promoting the use of public transportation and Intelligent Transport Systems, as well as improving transit accessibility for all citizens, may help in decreasing traffic congestion and air pollution ...in urban areas. In general, poor information to customers is one of the main issues in public transportation services, which is an important reason for allocating substantial efforts to implement a powerful and easy to use and access information tool. This paper focuses on the design and development of a real time mobility information system for the management of unexpected events, delays and service disruptions concerning public transportation in the city of Milan. Exploiting the information on the status of urban mobility and on the location of citizens, commuters and tourists, the system is able to reschedule in real time their movements. The service proposed stems from the state of the art in the field of travel planners for public transportation, available for Milan. Peculiarly, we built a representation of the city transit based on a time-expanded graph that considers the interconnections among all the stops of the rides offered during the day. The structure distinguishes the physical stations and the get on/get off stops of each ride, representing them with two different types of nodes. Such structure allows, with regard to the main focus of the project, to model a wide range of service disruptions, much more meaningful than those possible with approaches currently proposed by transit agencies. One of the most interesting point lies in the expressive capability in describing the different disruptions: with our model it is possible, for instance, to selectively inhibit getting on and/or off at a particular station, avoid specific rides, and model temporary deviations.
Research is a key factor for a successful reduction in greenhouse gas (GHG) emissions from transport. This article summarizes the main results of REACT, a project cofinanced by the European ...Commission, which aimed to develop a European Strategic Research Agenda for low GHG transport. A literature review and a multistage expert consultation process were used to map technological and nontechnological research areas and evaluate them according to different criteria (i.e., GHG emissions reduction, cost-efficiency, feasibility, time frame of research stages). We consulted the research agendas of the European Technologies Platforms on transport and current EU research programs. Expert opinions were collected through web forms, interviews, and participation in structured workshops. The REACT Research Agenda identified the following research priorities for a more climate-friendly transport system by 2030: (a) in the short term, cost-effective solutions consist of (1) more efficient, lighter vehicles with advanced internal combustion engines, (2) reducing road transport demand and (3) fostering GHG emission legislation; (b) in the medium/long term, the focus shifts toward (1) electric vehicles and hydrogen, (2) Intelligent Transport Systems, and (3) spatial planning and economic and social measures to reduce transport demand. In addition, one of the main findings identified strong links between technology research and planning, social sciences, and economy.
PoliUniPool: a carpooling system for universities Bruglieri, Maurizio; Ciccarelli, Diego; Colorni, Alberto ...
Procedia, social and behavioral sciences,
2011, 2011-00-00, Letnik:
20
Journal Article
Recenzirano
Odprti dostop
Carpooling is a transport system based on a shared use of private cars. The mobility managers of the Università Statale and Politecnico di Milano universities are interested in promoting the use of ...such system among their students and employees. The paper presents an ongoing project to design, implement and test PoliUniPool, a car pooling service for such universities. The main characteristics of the PoliUniPool service are the following: (1) the use of the system is restricted to employees, faculty and students of the two universities; (2) besides suggesting a matching between the users, the system provides the expected schedule for their trips; (3) in addition to the campus premises, users can select – as destination of their car pooling trips – the main railway and subway stations, in order to encourage the most environmental friendly means; (4) users are informed immediately in case of delay or changes, to improve the reliability of the service; (5) the system estimates the costs for each user, in order to let the users know how to share them; (6) the system has some social network functionalities, e.g. drivers are able to set partial pre-arranged crews; and users may indicate other users they would prefer to car-pool with (“friends”) or they don’t want to (“I don’t like him/her”). A web-based software tool has been implemented to manage the matching of the users. In order to solve the carpooling problem, we use an heuristics, based on a guided Monte Carlo method. The algorithm minimizes an objective function, subject to user time windows and car capacity constraints. The objective function is a weighted sum of different terms in order to maximize the number of served users, minimizing the total route length, and maximizing the satisfied user preferences (e.g. friends). The result is a matching between drivers and passengers, their schedules and the routes to be driven by each driver. The trial of the proposed service will start on September 2011 and will take into account how to introduce and promote the service, identifying regulation, incentives, modalities, and marketing actions.
A significant role among soft mobility measures to influence people's mobility choices and to raise awareness is played by the provision of targeted information. The integration of user-centered ...design, social innovation, portable devices, and sensors may have a role in influencing people's choices and consumption patterns. The paper presents two ongoing works that investigate, design and develop tools for valuing people's positive behaviors and rewarding choices in the domain of mobility and energy. The objective of such tools is both to raise people's awareness and to engage it into a collaborative environment, in order to meet a common set of targets. The strategy adopted in both the cases is based on linking “bottom-up” with “top-down” approach, i.e. by making people to behave and to make choices coordinately with decision maker's (i.e. the Public Administration or the Administrator of the system) objectives. The first regards Opti-LOG, a project co-funded by Regione Lombardia under the Smart Cities and Communities program, which concerns last-mile delivery with low emission and zero emission vehicles. The second case regards Sharing Cities, a H2020 project that includes a pilot project in the Municipality of Milano, where the focus is on citizen engagement and behaviors in the domains of personal mobility and energy. The system, by enabling mechanisms of collaboration, sharing and human capital generation, tackles the objectives of lowering energy consumption and promoting sustainable mobility and contributes to the weaving of a more cohesive social tissue.
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