Comprehensive Overview of Alzheimer’s Disease Neurodegeneration, from Amyloid-β to Neuroinflammatory Modulation

Alzheimer’s disease (AD) constitutes a major health threat to elder people. Despite the great advances achieved regarding our knowledge of the disease, we are far to successfully treat this pathology. Molecular alterations, immune/inflammatory response, and cell death are some of the processes involved during the pathology. Moreover, AD affects the whole brain. In this regard, we must not only consider the health status of neurons, of course, but also pay attention to the status of the glial cells and additional surrounding structures, such as the blood-brain barrier (BBB). Several groups have demonstrated how the molecular alterations occurring during AD alter neurons, glial, and endothelial cells. This situation has become so relevant that different groups are currently working to unveil the blank spaces in our understanding about the co-involvement of these elements in AD. Based in our experience, we believe that this kind of approach will lead to the design and development of more comprehensive therapeutical interventions. The present chapter summarizes the relevant aspects of state of the art regarding AD, from its molecular genesis to the recent advances in neuroinflammatory modulation, including nuclear receptors (NR), such as peroxisome proliferator-activated receptors (PPARs), and the Wnt pathway involved in the AD neurodegeneration

Propulsion Study for Small Transport Aircraft Technology (STAT)

Propulsion requirements were determined for 0.5 and 0.7 Mach aircraft. Sensitivity studies were conducted on both these aircraft to determine parametrically the influence of propulsion characteristics on aircraft size and direct operating cost (DOC). Candidate technology elements and design features were identified and parametric studies conducted to select the STAT advanced engine cycle. Trade off studies were conducted to determine those advanced technologies and design features that would offer a reduction in DOC for operation of the STAT engines. These features were incorporated in the two STAT engines. A benefit assessment was conducted comparing the STAT engines to current technology engines of the same power and to 1985 derivatives of the current technology engines. Research and development programs were recommended as part of an overall technology development plan to ensure that full commercial development of the STAT engines could be initiated in 1988

Toll-Like Receptors (TLRs) in Neurodegeneration: Integrative Approach to TLR Cascades in Alzheimer’s and Parkinson’s Diseases

Sterile inflammatory response constitutes a main event in several neurodegenerative disorders. Alzheimer’s disease (AD) and Parkinson’s disease (PD), the leading degenerative pathologies of the central nervous system worldwide, exhibit a strong inflammatory component. Microglial and astrocytic reactivity, increased levels of inflammatory mediators, neuronal damage, and death are part of the pathological scenario leading to the progressive failure of the brain neuronal network. In this regard, the link between the toll-like receptors (TLRs)-mediated inflammatory cascade and the molecular hallmarks of AD and PD have been demonstrated elsewhere. Moreover, the long-lasting exposure to the inflammatory environment is considered one of the key elements leading to the establishment and progression of these pathologies. Accordingly, the modulation of the inflammatory response has emerged as a main target of new therapeutic approaches to fight these diseases. In this regard, and based on our previous works on this subject, we describe the pathological profile of both pathologies but in the inflammatory context. Thus, in the present chapter, we will introduce the main aspects of both diseases and how they interplay with the TLR-mediated response. We believe that this chapter should provide a concise overview of the roles of TLRs in the inflammatory cascades triggered during AD and PD pathophysiology

Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases

Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute the main causes of dementia worldwide and the major health threats to elderly people. Moreover, with the ageing of the global population, neurodegenerative disorders, such as AD and PD, constitute a major public health issue. Regrettably, significant advances regarding the molecular aspects of these diseases have not yet been translated into real improvements in AD/PD therapeutics. In this regard, both AD and PD are highly complex and involve critical molecular events governing the establishment and progression of each disease. Moreover, molecular alterations trigger pathophysiological cascades involving the immune/inflammatory response, oxidative stress, and mitochondrial dysfunction, among others, ultimately leading to neuronal death. Similarly, these alterations also affect glial cells and brain vasculature, which contribute directly to the progression of these disorders. Accordingly, the present paper aims to summarise the main molecular elements related to AD and PD as well as the pathophysiological implications of such alterations to improve our understanding of the cellular and molecular responses observed during neurodegeneration. We believe that providing a more comprehensive view of the pathophysiological cascade, including neurons and glial cells, might prompt researchers to widen neurodegenerative disorder research and therapeutic approaches

Study of an advanced General Aviation Turbine Engine (GATE)

The best technology program for a small, economically viable gas turbine engine applicable to the general aviation helicopter and aircraft market for 1985-1990 was studied. Turboshaft and turboprop engines in the 112 to 746 kW (150 to 1000 hp) range and turbofan engines up to 6672 N (1500 lbf) thrust were considered. A good market for new turbine engines was predicted for 1988 providing aircraft are designed to capitalize on the advantages of the turbine engine. Parametric engine families were defined in terms of design and off-design performance, mass, and cost. These were evaluated in aircraft design missions selected to represent important market segments for fixed and rotary-wing applications. Payoff parameters influenced by engine cycle and configuration changes were aircraft gross mass, acquisition cost, total cost of ownership, and cash flow. Significant advantage over a current technology, small gas turbine engines was found especially in cost of ownership and fuel economy for airframes incorporating an air-cooled high-pressure ratio engine. A power class of 373 kW (500 hp) was recommended as the next frontier for technology advance where large improvements in fuel economy and engine mass appear possible through component research and development

Assessment of “Carbopeaking” in a hydropeaking-impacted river in the Italian Alpine area

Hydropeaking (i.e., rapid and frequent artificial flow fluctuations caused by reservoir-operated hydropower production) is a much-investigated river stressor, and has been associated, among others, to sudden changes in temperature (“thermopeaking”), underwater soundscape (“soundpeaking”), total dissolved gas saturation (“saturopeaking”). We have recently started investigating the “carbopeaking”, i.e., variations of greenhouse gas (mainly CO2) concentrations and evasion fluxes through the water-air interface associated with hydropeaks. Here we report on the methodology and preliminary results from a field-measurement campaign conducted in a single-thread Alpine river (River Noce, Italy) during multiple hydropeaking events. The analysis of water samples collected in the upstream reservoir showed CO2 oversaturation in the hypolimnion, around the depth of the hydropower intake system. In the Noce reach upstream of the hydropower plant outlet (i.e., in a residual flow stretch), the CO2 concentrations displayed diel fluctuations around the atmospheric equilibrium concentration, likely driven by diurnal primary production. Conversely, water released at the hydropower outlet during hydropeaking were consistently oversaturated in CO2 relative to the atmosphere, in agreement with the concentrations in the reservoir’s hypolimnetic water. As a result, hydropeaking events were associated with an alteration of the sub-daily patterns of CO2 concentration downstream of the hydropower outlet which, combined with higher gas exchange velocities occurring during higher flow rates, can cause periods of enhanced CO2 emissions. The results highlight the potential impact of hydropeaking on greenhouse gas emissions, demonstrating the need to account for sub-daily variations of flow and gas concentration to accurately quantify carbon balances in rivers impacted by hydropower

SMART Research: Toward Interdisciplinary River Science in Europe

Interdisciplinary science is rapidly advancing to address complex human-environment interactions. River science aims to provide the methods and knowledge required to sustainably manage some of the planet’s most important and vulnerable ecosystems; and there is a clear need for river managers and scientists to be trained within an interdisciplinary approach. However, despite the science community’s recognition of the importance of interdisciplinary training, there are few studies examining interdisciplinary graduate programs, especially in science and engineering. Here we assess and reflect on the contribution of a 9-year European doctoral program in river science: ‘Science for MAnagement of Rivers and their Tidal Systems’ Erasmus Mundus Joint Doctorate (SMART EMJD). The program trained a new generation of 36 early career scientists under the supervision of 34 international experts from different disciplinary and interdisciplinary research fields focusing on river systems, aiming to transcend the boundaries between disciplines and between science and management. We analyzed the three core facets of the SMART program, namely: (1) interdisciplinarity, (2) internationalism, and (3) management-oriented science. We reviewed the contents of doctoral theses and publications and synthesized the outcomes of two questionnaire surveys conducted with doctoral candidates and supervisors. A high percentage of the scientific outputs (80%) were interdisciplinary. There was evidence of active collaboration between different teams of doctoral candidates and supervisors, in terms of joint publications (5 papers out of the 69 analyzed) but this was understandably quite limited given the other demands of the program. We found evidence to contradict the perception that interdisciplinarity is a barrier to career success as employment rates were high (97%) and achieved very soon after the defense, both in academia (50%) and the private/public sector (50%) with a strong international dimension. Despite management-oriented research being a limited (9%) portion of the ensemble of theses, employment in management was higher (22%). The SMART program also increased the network of international collaborations for doctoral candidates and supervisors. Reflections on doctoral training programs like SMART contribute to debates around research training and the career opportunities of interdisciplinary scientists

On the long term behavior of meandering rivers

In spite of notable advances in the description of river morphodynamics, the long-term dynamics of meandering rivers is still an open question, in particular, regarding the existence of a possible statistical steady state and its scaling properties induced by the competing action of cutoffs and reach elongation. By means of extensive numerical simulations, using three fluid dynamic models of different complexity and analysis of real data from the Amazon, North America, and Russia, we show that the reach cutoffs, besides providing stability and self-confinement to the meander belt, also act as a dynamical filter on several hydrodynamic mechanisms, selecting only those that really dominate the long-term dynamics. The results show that the long-term equilibrium conditions are essentially governed by only one spatial scale (proportional to the ratio of the river depth and the friction coefficient) and one temporal scale (proportional to the square of the spatial scale divided by the river width, the mean longitudinal velocity, and the erodibility coefficient) that contain the most important fluid dynamic quantities. The ensuing statistical long-term behavior of meandering rivers proves to be universal and largely unaffected by the details of the fluid dynamic processes that govern the short-term river behavio