Prevention and treatment: Effects on pathological alterations in transgenic Alzheimer’s disease mouse models

Alzheimer’s disease (AD) is a neurodegenerative disorder representing the most common form of dementia worldwide. To date, no successful therapeutic approach to treat AD has been developed, hence preventive strategies started to become a major research focus. In this work, the effects of pharmacological treatment strategies such as chronic memantine, caffeine or riluzole supplementation, as well as the effect of a stimulating environmental living condition on the pathological alterations have been examined in Tg4-42hom and 5xFAD mice, representing two different AD mouse models. The Tg4-42 model overexpresses only the Aβ4-42 peptide mainly in the hippocampus, lacking any mutations linked to the familial form of the disease. Although this mouse model does not present overt extracellular Aβ plaques, Aβ4-42 forms neurotoxic aggregates that well correlate with the age- and dose-dependent pyramidal neuron loss in the CA1 region of the hippocampus as well as with robust learning and memory deficits. It could be shown that long-term oral treatment with either memantine, caffeine or riluzole completely rescued behavioural deficits in 6-month-old Tg4-42hom mice. Interestingly, these beneficial effects on learning and memory were accompanied by a significant amelioration of neuronal loss and a robust increase in neurogenesis. The present study presents evidence that long-term oral treatment with these drugs prevents behavioural decline as well as neuron loss and impaired neurogenesis in a mouse model reflecting the sporadic form of AD. Recently, epidemiological data revealed a potential protective role of physical exercise and cognitive stimulation on AD risk. Hence, it could be demonstrated in Tg4-42hom mice that living in a stimulating environment not only improves general behaviour but also ameliorates sensory-motor deficits. We have shown that the housing condition exerts a strong beneficial effect on a typical floating phenotype in Tg4-42hom mice, since none of the animals housed in an enriched environment presented that characteristic.The 5xFAD model is a well-characterized and commonly studied AD mouse model, reflecting first and foremost the familial form of the disease. In the present work, it could be demonstrated that, despite of an amelioration of memory deficits, chronic caffeine intake has no major influence on the typical pathophysiological alterations in the 5xFAD model, since neither changes with regard to Aβ plaque deposition, neuroinflammation, Aβ1-42 levels or APP processing were observed. These results suggest that a therapeutic intervention, such as chronic caffeine administration, might have a crucial impact on cognition without influencing the aggressive AD pathology observed in 5xFAD mice after onset of pathology.2022-05-1

Study and development of innovative strategies for energy-efficient cross-layer design of digital VLSI systems based on Approximate Computing

The increasing demand on requirements for high performance and energy efficiency in modern digital systems has led to the research of new design approaches that are able to go beyond the established energy-performance tradeoff. Looking at scientific literature, the Approximate Computing paradigm has been particularly prolific. Many applications in the domain of signal processing, multimedia, computer vision, machine learning are known to be particularly resilient to errors occurring on their input data and during computation, producing outputs that, although degraded, are still largely acceptable from the point of view of quality. The Approximate Computing design paradigm leverages the characteristics of this group of applications to develop circuits, architectures, algorithms that, by relaxing design constraints, perform their computations in an approximate or inexact manner reducing energy consumption. This PhD research aims to explore the design of hardware/software architectures based on Approximate Computing techniques, filling the gap in literature regarding effective applicability and deriving a systematic methodology to characterize its benefits and tradeoffs. The main contributions of this work are: -the introduction of approximate memory management inside the Linux OS, allowing dynamic allocation and de-allocation of approximate memory at user level, as for normal exact memory; - the development of an emulation environment for platforms with approximate memory units, where faults are injected during the simulation based on models that reproduce the effects on memory cells of circuital and architectural techniques for approximate memories; -the implementation and analysis of the impact of approximate memory hardware on real applications: the H.264 video encoder, internally modified to allocate selected data buffers in approximate memory, and signal processing applications (digital filter) using approximate memory for input/output buffers and tap registers; -the development of a fully reconfigurable and combinatorial floating point unit, which can work with reduced precision formats

Different strategies for improving summer thermal comfort in heavyweight traditional buildings

In order to exploit the passive energy potential of the building envelope, it is important to provide a right combination of insulation thickness, heat capacity and night-time ventilation. In this paper, this issue will be tackled with reference to an historic building in Catania (Southern Italy). The building was built at the end of the XIX century, and its opaque envelope is entirely made with lava stones, which is typical of traditional architecture in this area. Starting from the current configuration of the building, many hypotheses for refurbishment are considered, combined with different strategies for passive cooling, such as night-time ventilation, use of shading devices and adoption of highly-reflective coatings. The effectiveness of each solution in terms of summer thermal comfort is evaluated through dynamic thermal simulations carried out with EnergyPlus. The results show the synergic effect of these strategies, as well as their individual impact, and allow to draw some general conclusions about the behaviour of heavyweight buildings under moderately hot weather conditions

Application of Small Epigenetic Modulators in Pediatric Medulloblastoma

Medulloblastoma is one of the most frequent among pediatric brain tumors, and it has been classified in various subgroups. Some of them already benefit from quite good therapeutic options, whereas others urgently need novel therapeutic approaches. Epigenetic modulators have long been studied in various types of cancer. Within this review, we summarize the main preclinical studies regarding epigenetic targets (such as HDAC, SIRT, BET, EZH2, G9a, LSD1, and DNMT) inhibitors in medulloblastoma. Furthermore, we shed light on the increasing number of applications of drug combinations as well as hybrid compounds involving epigenetic mechanisms. Nevertheless, in the studies published so far, mainly un-specific or old modulators have been used, and the PKs (brain permeability) have not been well-evaluated. Thus, these findings should be considered as a starting point for further improvement and not as a final result

Traditional Houses with Stone Walls in Temperate Climates: The Impact of Various Insulation Strategies

The present chapter focuses on the yearly behaviour of a traditional farmhouse in a temperate Italian climate and analyses the impact of alternative energy saving strategies on summer comfort and winter consumptions. The aim of the current study was to: - identify combinations of thermal insulation interventions which: optimise winter energy saving and summer internal comfort without modifying the close relationship between architecture and specific climate typical of traditional buildings; respect the building material consistency and the façades aesthetic appearance. - compare the performance of this traditional architecture (after the retrofit intervention) with that of a modern building, of the type encouraged by new energy saving legislation (lightweight and super-insulated). To that aim a series of monitoring activities in summer and in winter were carried out to investigate the internal environmental conditions and to calibrate a simulation model with the software Energyplus. This model was used to assess the impact of various energy-saving strategies on winter energy consumptions and summer comfort with the method of Percentage outside the comfort range (EN 15251:2007-08)

Medical records confidentiality and public health research: two values at stake? An italian survey focus on individual preferences

In a time when Europe is preparing to introduce new regulations on privacy protection, we conducted a survey among 1700 twins enrolled in the Italian Twin Register about the access and use of their medical records for public health research without explicit informed consent. A great majority of respondents would refuse or are doubtful about the access and use of hospital discharge records or clinical data without their explicit consent. Young and female individuals represent the modal profile of these careful people. As information retrieved from medical records is crucial for progressing knowledge, it is important to promote a better understanding of the value of public health research activities among the general population. Furthermore, public opinions are relevant to policy making, and concerns and preferences about privacy and confidentiality in research can contribute to the design of procedures to exploit medical records effectively and customize the protection of individuals’ medical data

Quality aware selective ECC for approximate DRAM

Approximate DRAMs are DRAM memories where energy saving techniques have been implemented by trading off bit-cell error rate with power consumption. They are considered part of the building blocks in the larger area of approximate computing. Relaxing refresh rate has been proposed as an interesting solution to achieve better efficiency at the expense of rising error rate. However, some works have demonstrated that much better results are achieved if at word-level some bits are retained without errors (i.e. their cells are refreshed at nominal rate), resulting in architectures using multiple refresh rates. In this paper we present a technique that can be applied to approximate DRAMs under reduced refresh rate. It allows to trim error rate at word-level, while still performing the refresh operation at the same rate for all cells. The number of bits that are protected is configurable and depends on output quality degradation that can be accepted by the application

Cob Construction in Italy: Some Lessons from the Past

Raw earth is a construction material unknown to most people. Nowadays, raw-earth constructions are an area of growing interest, both for rescuing the heritage and for a rediscovered environmentally friendly building and eco-sustainability material. However, because raw-earth constructions are a forgotten technique, we find problems of a lack of skilled people at all levels in this area, from designers to masons, as well as problems of how to carry out compatible conservation works on earthen heritage. This paper tries to fill the gap for a peculiar historic earthen building technology, namely cob (or bauge), which is present in Macerata in the center of Italy. Results are presented on regaining possession of the material and constructional aspects and their initial structural resources, and guidelines are given on how to improve the manufacturing process to reuse the cob technique for construction and for how to accurately work on it for a compatible and sustainable conservation

Copper distribution among physical and chemical fractions in a former vineyard soil

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\u3ci\u3eCheilosia corydon\u3c/i\u3e (Diptera: Syrphidae)., a Candidate for the Biological Control of Musk Thistle in North America

In Italy, larvae of the syrphid fly, Cheilosia corydon (Harris) (=grossa Fallen), infest the flower buds, stems, and roots of Carduus nutans L. and C. pycnocephalus L. (Compositae), both serious weeds in the United States. The fly was studied as a candidate biological control agent of musk and Italian thistle in North America. The host range of C. corydon is narrow, restricted to plants of the tribe Cardueae. Cirsium crassicaule (Green) Jeps., a threatened U.S. species, was marginally suitable as a host in laboratory trials. In open-field oviposition tests, using replicated and randomized plantings, no oviposition was observed on any U.S. Cirsium species tested, including C. crassicaule. Our data indicate that C. corydon is sufficiently host specific to introduce into the U.S. for the biological control of musk and Italian thistle