Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy

The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1, or HSP60, or Cpn60) and CCT (chaperonin-containing TCP-1). Our aim is to make scientists and physicians aware of the possibility and advantages of classifying patients depending on the presence or absence of a chaperonopathy. In turn, this subclassification will allow the development of novel therapeutic strategies (chaperonotherapy) by using molecular chaperones as agents or targets for treatment

Distinguishing the “Truly National” From the “Truly Local”: Customary Allocation, Commercial Activity, and Collective Action

This Essay makes two claims about different methods of defining the expanse and limits of the Commerce Clause. My first claim is that approaches that privilege traditional subjects of state regulation are unworkable and undesirable. These approaches are unworkable in light of the frequency with which the federal government and the states regulate the same subject matter in our world of largely overlapping federal and state legislative jurisdiction. The approaches are undesirable because the question of customary allocation is unrelated to the principal reason why Congress possesses the power to regulate interstate commerce: solving collective action problems involving multiple states. These problems are evident in the way that some federal judges invoked regulatory custom in litigation over the constitutionality of the minimum coverage provision in the Patient Protection and Affordable Care Act. The areas of health insurance and health care are not of exclusive state concern, and it is impossible to lose—or to win—a competition requiring skillful lawyers or judges to describe them as more state than federal, or more federal than state. Nor is it most important what the answer is. More promising are the approaches that view congressional authority as turning on either commercial activity or collective action problems facing the states. My second claim is that these two approaches have advantages and disadvantages, and that the choice between them exemplifies the more general tension between applying rules and applying their background justifications. I have previously defended a collective action approach to Article I, Section 8. My primary purpose in this Essay is to clarify the jurisprudential stakes in adopting one method or the other and to identify the problems that advocates of each approach must address

The Constitutionality of Mandates to Purchase Health Insurance

Health insurance mandates have been a component of many recent health care reform proposals. Because a federal requirement that individuals transfer money to a private party is unprecedented, a number of legal issues must be examined. This paper analyzes whether Congress can legislate a health insurance mandate and the potential legal challenges that might arise, given such a mandate. The analysis of legal challenges to health insurance mandates applies to federal individual mandates, but can also apply to a federal mandate requiring employers to purchase health insurance for their employees. There are no Constitutional barriers for Congress to legislate a health insurance mandate as long as the mandate is properly designed and executed, as discussed below. This paper also considers the likelihood of any change in the current judicial approach to these legal questions

Development of a Vessel Scheduling Optimization Model to improve Maritime Transport sustainability

The social and economic development of the islands is generally dependent on the interconnection level with the mainland obtained through maritime transport services. When connecting many islands, the route planning is essential and typically a variety of constraints must be considered. Various optimization methods have been established to improve cost-efficiency but today environmental concerns, like the reduction of CO2 emissions, have become mandatory. This paper proposes a vessel scheduling optimization model able to simultaneously consider compulsory and optional tasks and vehicle-dependent profits. The algorithm was applied to seven islands of the Tyrrhenian Sea located in front of Sicily, named “Aeolian Islands”. Considering the regional requirements in terms of minimum number of routes and maximum fare prices for each season, this research compared the optimal vessels option obtained maximizing the profit with the one obtained minimizing the emissions. In particular, we have conducted three different analyses, in the first one we have considered only the mandatory routes while the second one was carried out identifying a series of potentially attractive additional activities based on historical demand data provided by the company that currently manages the service. Finally, the third analysis addresses a scenario where older fuel-powered vessels were replaced with hybrid electric ones

Consideration of Reaction Forces of Holonomic Constraints as Generalized Coordinates in Approximate Determination of Lower Frequencies of Elastic Systems

A new method for determination of lower frequencies of mechanical systems consisting of elastic bodies connected to each other is offered. The conditions of connection of bodies are written as holonomic constraints, the reactions of which are considered as generalized coordinates. Therefore the number of degrees of freedom proves to be equal to the number of constraints

Project management information systems (Pmiss): A statistical-based analysis for the evaluation of software packages features

Project Managers (PMs) working in competitive markets are finding Project Management Information Systems (PMISs) useful for planning, organizing and controlling projects of varying complexity. A wide variety of PMIS software is available, suitable for projects differing in scope and user needs. This paper identifies the most useful features found in PMISs. An extensive literature review and analysis of commercial software is made to identify the main features of PMISs. After-wards, the list is reduced by a panel of project management experts, and a statistical analysis is performed on data acquired by means of two different surveys. The relative importance of listed features is properly computed, and the interactions between the respondent’s profiles and PMIS features are also investigated by cluster and respondents’ analyses. The paper provides information for researchers and practitioners interested in PMISs packages and their applications. Furthermore, the analyses may help practitioners when choosing a PMIS, and also for developers of PMISs software in understanding user needs

Occupational health and safety issues in human-robot collaboration: State of the art and open challenges

Human-Robot Collaboration (HRC) refers to the interaction of workers and robots in a shared workspace. Owing to the integration of the industrial automation strengths with the inimitable cognitive capabilities of humans, HRC is paramount to move towards advanced and sustainable production systems. Although the overall safety of collaborative robotics has increased over time, further research efforts are needed to allow humans to operate alongside robots, with awareness and trust. Numerous safety concerns are open, and either new or enhanced technical, procedural and organizational measures have to be investigated to design and implement inherently safe and ergonomic automation solutions, aligning the systems performance and the human safety. Therefore, a bibliometric analysis and a literature review are carried out in the present paper to provide a comprehensive overview of Occupational Health and Safety (OHS) issues in HRC. As a result, the most researched topics and application areas, and the possible future lines of research are identified. Reviewed articles stress the central role played by humans during collaboration, underlining the need to integrate the human factor in the hazard analysis and risk assessment. Human-centered design and cognitive engineering principles also require further investigations to increase the worker acceptance and trust during collaboration. Deepened studies are compulsory in the healthcare sector, to investigate the social and ethical implications of HRC. Whatever the application context is, the implementation of more and more advanced technologies is fundamental to overcome the current HRC safety concerns, designing low-risk HRC systems while ensuring the system productivity

Life cycle analysis of innovative building materials based on circular coffee ground supply chain

The construction sector is widely recognized as one of the most polluting mainly due to its intensive exploitation of natural resources and large energy consumption to produce traditional building materials. In the last years, alternative building materials have been developed with the aim to reduce the environmental burden of this sector. In particular, the use of geopolymer mortars as alternative cementitious materials is gaining increasing acceptance among scientists. Numerous laboratory studies demonstrate their suitability for construction applications, highlighting the potential environmental benefits that can be obtained from their large-scale production. This study aims to perform a preliminary evaluation of the environmental performance of a geopolymer mortar, whose production includes the reuse of a food waste: Spent Coffee Ground (SCG). By using the Life Cycle Assessment (LCA) approach, an environmental comparison with a traditional production of cement mortar was carried out on the basis of the Global Warming Potential (GWP) indicator

Generation of cytocompatible superhydrophobic Zr–Cu–Ag metallic glass coatings with antifouling properties for medical textiles

Zirconium–Copper-based metallic glass thin films represent promising coatings in the biomedical sector for their combination of antibacterial property and wear resistance. However, finding a Zr–Cu metallic glass composition with desirable cytocompatibility and antibacterial property is extremely challenging. In this work, we have created a cytocompatible and (super-)hydrophobic Zr–Cu–Ag metallic glass coating with ≈95% antifouling properties. First, a range of different chemical compositions were prepared via Physical Vapor Deposition magnetron by co-sputtering Zr, Cu, and Ag onto a Polybutylene terephthalate (PBT) substrate among which Zr93·5Cu6·2Ag0.2, Zr76·7Cu22·7Ag0.5, and Zr69·3Cu30·1Ag0.6 were selected to be further investigate for their surface properties, antibacterial activity, and cytocompatibility. Scanning electron microscopy (SEM) images revealed a micro-roughness fibrous structure holding superhydrophobic properties demonstrated by specimens' static and dynamic contact angle measurements ranging from 130° to 150°. The dynamic contact angle measurements have shown hysteresis below 10° for all coated samples which indicated the superhydrophobicity of the samples. To distinguish between antifouling and bactericidal effect of the coating, ions release from coatings into Luria Bertani Broth (LB), and Dulbecco's Modified Eagle Medium (DMEM) solutions were evaluated by inductively coupled plasma mass spectrometry (ICP-MS) measurements after 24 ​h and 5 days. Antifouling properties were evaluated by infecting the specimens' surface with the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli strain reporting a ≈95% reduction of bacteria adhesion as visually confirmed by FESEM and fluorescent live/dead staining. Human mesenchymal stem cells (hMSC) were used for direct cytocompatibility evaluation of coated samples and their metabolic activity was evaluated via relative fluorescence unit after 24 ​h and 5 days confirming that it was comparable to the controls (>97% viable cells). The results were further visualized by FESEM, fluorescent staining by Live/Dead Viability/Cytotoxicity Kit and confirmed the cytocompatibility of all coated samples. Finally, hMSC′ cytoplasm was stained by May Grunwald and Giemsa after 5days to detect and visualize the released ions which have diffused through the cells' membrane