Towards a methodology for new technologies assessment in aircraft operating cost

The need for a greener and competitive aircraft is leading to the use of new technologies. A thorough assessment of these technologies is mandatory from the initial phases of aircraft design to understand their feasibility and to select the most promising one both in terms of performances and in terms of costs. This paper proposes a methodology to assess the operating cost of innovative technologies for regional aircraft. In particular, two NASA studies have been adopted to determine the impact onto costs of MEA and AEA technologies and advanced ECS solutions for two innovative regional aircraft concepts developed during the European Clean Sky 2 research. The proposed methodology is able to assess the effect of on-board systems electrification level in terms of fuel and maintenance costs savings. The methodology, which allows to evaluate the effect of specific technological improvements onto costs, is applied exploiting the results provided by a reliable cost model and gives the opportunity to quantify operating cost savings for different regional aircraft. Applying the modified cost model to the reference aircraft under study, savings ranging from 1.6 to 3.1% of direct operating cost are estimated for MEA and AEA technologies. Greater savings are estimated for the individual cost items involved. More specifically, a reduction of fuel cost ranging from 6 to 14.5% is envisaged as a consequence of the lower SFC associated to innovative ECS technologies

Distributed Generation and Resilience in Power Grids

We study the effects of the allocation of distributed generation on the resilience of power grids. We find that an unconstrained allocation and growth of the distributed generation can drive a power grid beyond its design parameters. In order to overcome such a problem, we propose a topological algorithm derived from the field of Complex Networks to allocate distributed generation sources in an existing power grid.Comment: proceedings of Critis 2012 http://critis12.hig.no

Encrusted cystitis in an immunocompromised patient: possible coinfection by Corynebacterium urealyticum and E. coli.

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Advanced Video-Based Processing for Low-Cost Damage Assessment of Buildings under Seismic Loading in Shaking Table Tests

This paper explores the potential of a low-cost, advanced video-based technique for the assessment of structural damage to buildings caused by seismic loading. A low-cost, high-speed video camera was utilized for the motion magnification processing of footage of a two-story reinforced-concrete frame building subjected to shaking table tests. The damage after seismic loading was estimated by analyzing the dynamic behavior (i.e., modal parameters) and the structural deformations of the building in magnified videos. The results using the motion magnification procedure were compared for validation of the method of the damage assessment obtained through analyses of conventional accelerometric sensors and high-precision optical markers tracked using a passive 3D motion capture system. In addition, 3D laser scanning to obtain an accurate survey of the building geometry before and after the seismic tests was carried out. In particular, accelerometric recordings were also processed and analyzed using several stationary and nonstationary signal processing techniques with the aim of analyzing the linear behavior of the undamaged structure and the nonlinear structural behavior during damaging shaking table tests. The proposed procedure based on the analysis of magnified videos provided an accurate estimate of the main modal frequency and the damage location through the analysis of the modal shapes, which were confirmed using advanced analyses of the accelerometric data. Consequently, the main novelty of the study was the highlighting of a simple procedure with high potential for the extraction and analysis of modal parameters, with a special focus on the analysis of the modal shape's curvature, which provides accurate information on the location of the damage in a structure, while using a noncontact and low-cost method

Multidisciplinary Design and Optimization of Regional Jet Retrofitting Activity

A retrofit analysis on a 90 passengers regional jet aircraft is performed through a multidisciplinary collaborative aircraft design and optimization highlighting the impact on costs and performance. Two different activities are accounted for selecting the best aircraft retrofit solution: a re-engining operation that allows to substitute a conventional power-plant platform with advanced geared turbofan and an on-board-systems architecture modernization, considering different levels of electrification. Besides the variables that are directly dependent from these activities, also scenario variables are considered during the optimization such as the fuel price, the fleet size and the years of utilization of the upgraded systems. The optimization is led by impacts of the retrofitting process on emissions, capital costs and saving costs, computed at industrial level. Overall aircraft design competences (aerodynamics, masses, performance, noise, and emissions) have been computed increasing the level of fidelity and reliability. The whole process is implemented in the framework of the AGILE 4.0 research project in a collaborative remote multidisciplinary approach. Results show that the engine retrofitting can be a profitable solution for both manufacturers and airliners. Conversely, the on-board-system electrification seems to be not convenient in a retrofitting process due to the high capital costs. Depending on the operative scenario, involved stakeholders can properly orient their decision on a retrofitting strategy

Cell Type-Specific Neuroprotective Activity of Untranslocated Prion Protein

Background: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP). However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. Principal Findings: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. Significance: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function

Immunopurification of Pathological Prion Protein Aggregates

Background: Prion diseases are fatal neurodegenerative disorders that can arise sporadically, be genetically inherited or acquired through infection. The key event in these diseases is misfolding of the cellular prion protein (PrP) into a pathogenic isoform that is rich in β-sheet structure. This conformational change may result in the formation of PrP, the prion isoform of PrP, which propagates itself by imprinting its aberrant conformation onto PrP molecules. A great deal of effort has been devoted to developing protocols for purifying PrP for structural studies, and testing its biological properties. Most procedures rely on protease digestion, allowing efficient purification of PrP27-30, the protease-resistant core of PrP. However, protease treatment cannot be used to isolate abnormal forms of PrP lacking conventional protease resistance, such as those found in several genetic and atypical sporadic cases. Principal Findings: We developed a method for purifying pathological PrP molecules based on sequential centrifugation and immunoprecipitation with a monoclonal antibody selective for aggregated PrP. With this procedure we purified full-length PrP and mutant PrP aggregates at electrophoretic homogeneity. PrP purified from prion-infected mice was able to seed misfolding of PrP in a protein misfolding cyclic amplification reaction, and mutant PrP aggregates from transgenic mice were toxic to cultured neurons. Significance: The immunopurification protocol described here isolates biologically active forms of aggregated PrP. These preparations may be useful for investigating the structural and chemico-physical properties of infectious and neurotoxic PrP aggregates

Expression of Mutant or Cytosolic PrP in Transgenic Mice and Cells Is Not Associated with Endoplasmic Reticulum Stress or Proteasome Dysfunction

The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known. Several mutant PrPs misfold in the early secretory pathway and reside longer in the endoplasmic reticulum (ER) possibly stimulating ER stress-related pathogenic mechanisms. To investigate whether mutant PrP induced maladaptive responses, we checked key elements of the unfolded protein response (UPR) in transgenic mice, primary neurons and transfected cells expressing two different mutant PrPs. Because ER stress favors the formation of untranslocated PrP that might aggregate in the cytosol and impair proteasome function, we also measured the activity of the ubiquitin proteasome system (UPS). Molecular, biochemical and immunohistochemical analyses found no increase in the expression of UPR-regulated genes, such as Grp78/Bip, CHOP/GADD153, or ER stress-dependent splicing of the mRNA encoding the X-box-binding protein 1. No alterations in UPS activity were detected in mutant mouse brains and primary neurons using the UbG76V-GFP reporter and a new fluorogenic peptide for monitoring proteasomal proteolytic activity in vivo. Finally, there was no loss of proteasome function in neurons in which endogenous PrP was forced to accumulate in the cytosol by inhibiting cotranslational translocation. These results indicate that neither ER stress, nor perturbation of proteasome activity plays a major pathogenic role in prion diseases

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Chronic Viral Infection and Primary Central Nervous System Malignancy

Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have been detected with varied frequencies in a number of pediatric and adult histological tumor subtypes. However, establishing a link between chronic viral infection and primary CNS malignancy has been an area of considerable controversy, due in part to variations in detection frequencies and methodologies used among researchers. Since a latent viral neurotropism can be seen with a variety of viruses and a widespread seropositivity exists among the population, it has been difficult to establish an association between viral infection and CNS malignancy based on epidemiology alone. While direct evidence of a role of viruses in neuro-oncogenesis in humans is lacking, a more plausible hypothesis of neuro-oncomodulation has been proposed. The overall goals of this review are to summarize the many human investigations that have studied viral infection in primary CNS tumors, discuss potential neuro-oncomodulatory mechanisms of viral-associated CNS disease and propose future research directions to establish a more firm association between chronic viral infections and primary CNS malignancies