1,348 research outputs found
Fare inspection in proof-of-payment transit networks: A review
In proof-of-payment transit systems worldwide, fare inspection is the most widely adopted strategy against fare evasion from transit authorities and public transport companies. Although these actors attempt to make the inspectorsâ work as easy, effective, and equitable as possible, several issues need to be analysed according to a unifying approach, i.e., âHow, where and when to inspectâ, âWho and why evades the fareâ, âHow many and how to distribute inspectorsâ as well as improve the inspectorsâ effectiveness. Since no study exists in the literature investigating all these issues together, this paper aims to fill this gap with a review of several key papers that covered the full spectrum of relevant literature which, whole or partially, focused on fare inspection. Results show fare inspection is a beneficial strategy against fare evasion, but there are still many challenges and research limits that should be overcome in the years ahead. A possible research agenda is provided. It calls for specific options (i.e., data collection and fare evasion risk in hotspot definition, digital support and bottom-up approaches, size of inspection staff and scheduling of inspectors under realistic conditions and follower responses, effectiveness of actions focused on the visibility of fare inspection, managing interactions between fare inspectors and passengers) and integrated approaches (i.e., linking the planning, organisation, and activities of fare inspection with who and why evade). Nevertheless, even if this review may not be conclusive, these results support a unifying literature development on fare inspection
Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis
Abstract Background Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis. Method The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression. Results Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments. Conclusions Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes
Sustainable cycle-tourism for society: Integrating multi-criteria decision-making and land use approaches for route selection
Cycle tourism is a sustainable active vacation, which is quickly growing in recent years. Although it has several benefits for society and users (e.g., social connections, amusement, and physical and mental health), cycle tourism requires an adequate route network to enjoy destinations with historical and landscape peculiarities. Past literature mainly investigated motivations and preferences for cycle tourists and proposed optimisation methods in planning routes. However, applying assessment methods for prioritising cycle-tourist routes is a seldom-explored topic. This study aims to address this gap by applying an integrated method for evaluating and prioritising cycle routes, searching for a compromise between route characteristics, service provided to users, and natural and building contexts crossed. It jointly includes Multi-Criteria Decision Methods (MCDMs) and a land use approach: AHP determines the weights of criteria and parameters describing cycle routes; GIS elaborates spatial analysis of parameters; ELECTRE I and VIKOR help find a compromise solution amongst different cycle routes. The integrated method involved a panel of experts to collect data, and it is applied to the wide-study area of Franciacorta (Italy). Some comparisons with other MCDMs are made to justify the results. The findings could support multi-institutions prioritising cycle route alternatives in deciding their building
Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site
<p>Abstract</p> <p>Background</p> <p>Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.</p> <p>Results</p> <p>We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ÎH of -13 ± 2 kJ/mol and a ÎS of -0.04 ± 0.01 kJ/(K*mol). The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site.</p> <p>Conclusion</p> <p>We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the geometric relationship of arginine-tryptophan pairs, which often have significant roles in protein function. Using the unusual characteristics of the RTA system, we measured the still controversial thermodynamic changes of site-specific urea binding to a protein, results that are relevant to understanding the physical mechanisms of protein denaturation.</p
Measuring Safety Performance in the extra-urban Road Network of Lombardy Region (Italy)
Road Network Screening (RNS) is a process to evaluate the safety performance of the whole road network and identify worst performing roads. Currently, literature provides many models and methods for RNS. Moreover, several frameworks of RNS were issued at the European National Level over time. However, even if sophisticated models and methods could be preferable for their computational accuracy, they may be far from the capabilities of practitioners. In addition, other issues such as availability of operative attributes and data quality and processing persist. For instance, accurate crash location, which is crucial for detailed analyses of high crash rates at some locations, is still an issue: many road administrations pointed out that coordinates miss or are inaccurate in many cases. Within this context, this paper proposes a straightforward operational framework to evaluate safety performance for RNS, using a flexible rationale that integrates crash, traffic, and road data, respectively. More precisely, this framework: (a) handles crash location data without using spatial coordinates; (b) computes the crash rate index at different administrative levels; (c) shows results by Geographic Information System (GIS) maps. This framework is applied to the whole extra-urban road network of the Lombardy Region (Northern Italy) using 30.000+ crash data provided by the Regional Institute for Lombardy Policy Support (PoliS). Road authorities could adopt this framework to perform an accurate safety screening on the road network aimed at rational planning of safety interventions
Evaluating alternative fuels for a bus fleet: An Italian case
A current topic that has surfaced among Public Transport Companies (PTCs) is the selection of alternative fuels for their bus fleets. Both European and Italian regulations are pushing toward abandoning diesel fuel and the consolidation of alternative traction power sources, such as battery-electric vehicles, fuel-cell electric vehicles, and hydrogen-electric vehicles. The literature has provided some approaches toward assessing this selection such as multicriteria-decision-methods in some countries in the world. However, not enough specific attention has been paid to cost criteria, experts involved, and the type of service required. This paper intends to address these gaps by applying an integrated method, which includes: (i) the Analytical Hierarchy Process (AHP) to define the weights of criteria; (ii) the ELimination Et Choix Traduisant la REaliteÌ I (ELECTRE I) to find a good compromise solution among the fuel alternatives and (iii) a simple Weighted Sum Model (WSM) to refine ranking. This integrated method was applied in Italy involving a panel of experts from whom the data was collected. Different fuel alternatives for both urban and interurban services and with and without funding are discussed. The results provide a useful tool supporting PTC policies, which aims to rationalise and prioritise bus fuel alternatives when deciding on fleet renewal
A comparative cycling path selection for sustainable tourism in Franciacorta. An integrated AHP-ELECTRE method
Cycle tourism is a form of sustainable itinerant tourism expanding in Italy and the rest of the world, with prospects for growth in coming years. Europe and North America have already developed a wide range of cycling infrastructures tied to tourism experiences. Benefits induced are generally recognised: first, it is a sustainable solution that increases local economics while conserving the environment; second, it guarantees advantages on social connections, amusement, and physical and mental health. However, it requires an adequate network to enjoy destinations as historical and landscape peculiarities. Currently, literature provides some methods for planning itineraries dedicated to cycle tourism. Despite that, there is less attention on how evaluating existing or already planned tourist itineraries. This study covers this gap, by applying an integrated method to assess bicycle connections for tourism experiences within municipalities. Since this evaluation may contain many conflicting criteria (e.g., preferences of public administrator, technical and economic viability) and possible alternatives, this study frames the method as a multi-criteria decision-making problem (MCDM). Specifically, at first, the Analytical Hierarchy Process (AHP) is adopted to calculate weights for each criterium; next, the ELimination Et Choix Traduisant la REalitĂš (ELECTRE) method is applied to provide a (possible) priority ranking of cycling tourist paths among alternatives, by computing indices of discordance and concordance between pairs of alternatives. The framework is applied to the Franciacorta area (North-East Italy), a national and international tourist relevance territory encompassing 22 municipalities. This study may be useful for public administrators to rationalise and prioritise cycling routes
BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes
Three missense mutations targeting the same proline 209 (Pro209) codon in the co-chaperone Bcl2-associated athanogene 3 (BAG3) have been reported to cause distal myopathy, dilated cardiomyopathy or Charcot-Marie-Tooth type 2 neuropathy. Yet, it is unclear whether distinct molecular mechanisms underlie the variable clinical spectrum of the rare patients carrying these three heterozygous Pro209 mutations in BAG3. Here, we studied all three variants and compared them to the BAG3_Glu455Lys mutant, which causes dilated cardiomyopathy. We found that all BAG3_Pro209 mutants have acquired a toxic gain-of-function, which causes these variants to accumulate in the form of insoluble HDAC6- and vimentin-positive aggresomes. The aggresomes formed by mutant BAG3 led to a relocation of other chaperones such as HSPB8 and Hsp70, which, together with BAG3, promote the so-called chaperone-assisted selective autophagy (CASA). As a consequence of their increased aggregation-proneness, mutant BAG3 trapped ubiquitinylated client proteins at the aggresome, preventing their efficient clearance. Combined, these data show that all BAG3_Pro209 mutants, irrespective of their different clinical phenotypes, are characterized by a gain-of-function that contributes to the gradual loss of protein homeostasis
Tumor suppressors in chronic lymphocytic leukemia: From lost partners to active targets
Tumor suppressors play an important role in cancer pathogenesis and in the modulation of resistance to treatments. Loss of function of the proteins encoded by tumor suppressors, through genomic inactivation of the gene, disable all the controls that balance growth, survival, and apoptosis, promoting cancer transformation. Parallel to genetic impairments, tumor suppressor products may also be functionally inactivated in the absence of mutations/deletions upon post-transcriptional and post-translational modifications. Because restoring tumor suppressor functions remains the most effective and selective approach to induce apoptosis in cancer, the dissection of mechanisms of tumor suppressor inactivation is advisable in order to further augment targeted strategies. This review will summarize the role of tumor suppressors in chronic lymphocytic leukemia and attempt to describe how tumor suppressors can represent new hopes in our arsenal against chronic lymphocytic leukemia (CLL)
Comment on ``Spin Polarization and Magnetic Circular Dichroism in Photoemission from the 2p Core Level of Ferromagnetic Ni''
Although the Ni_4 cluster includes more information regarding the Ni band
structure with respect to the Anderson impurity model, it also favors very
peculiar ground states which are incompatible with a coherent picture of all
dichroism experiments.Comment: 1 page, RevTeX, 1 epsf figur
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