Nrf2 Signaling: An Adaptive Response Pathway for Neurodegenerative Disorders

Oxidative damage contributes to pathogenesis in many neurodegenerative diseases. As the indicator and regulator of oxidative stress, the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway has been shown to have dynamic changes and examined for its neuroprotective role in many cases. Nrf2 is emerging as a regulatory protein in neuronal death, since it helps neuronal cells to meet with oxidative insults. In this chapter, we summarize the role of Nrf2 as a master regulator of oxidative stress. Furthermore, we treat some natural and chemical substances able to modulate the Nrf2 pathway and, therefore, their possible use in the neurodegenerative diseases therapeutic treatment

The Effects of Deregulating Retail Operating Hours: Empirical Evidence from Italy

We estimate the impact of deregulating shop hours on the structure of the retail sector and the size and composition of its labor force. To identify the effect of interest, we exploit the staggered implementation of a reform that allowed Italian municipalities to adopt fully flexible operating hours in the late 1990s. Our findings indicate that lifting restrictions on hours increased retail employment by 2.4 percent and increased the number of shops in the affected municipalities by 1.8 percent. In combination with estimates using individual-level data, our results further suggest that retail employment grew more in larger retail operations, with a corresponding movement of the labor force toward permanent employees and away from the self-employed

Fluids mobilization in Arabia Terra, Mars: depth of pressurized reservoir from mounds self-similar clustering

Arabia Terra is a region of Mars where signs of past-water occurrence are recorded in several landforms. Broad and local scale geomorphological, compositional and hydrological analyses point towards pervasive fluid circulation through time. In this work we focus on mound fields located in the interior of three casters larger than 40 km (Firsoff, Kotido and unnamed crater 20 km to the east) and showing strong morphological and textural resemblance to terrestrial mud volcanoes and spring-related features. We infer that these landforms likely testify the presence of a pressurized fluid reservoir at depth and past fluid upwelling. We have performed morphometric analyses to characterize the mound morphologies and consequently retrieve an accurate automated mapping of the mounds within the craters for spatial distribution and fractal clustering analysis. The outcome of the fractal clustering yields information about the possible extent of the percolating fracture network at depth below the craters. We have been able to constrain the depth of the pressurized fluid reservoir between ~2.5 and 3.2 km of depth and hence, we propose that mounds and mounds alignments are most likely associated to the presence of fissure ridges and fluid outflow. Their process of formation is genetically linked to the formation of large intra-crater bulges previously interpreted as large scale spring deposits. The overburden removal caused by the impact crater formation is the inferred triggering mechanism for fluid pressurization and upwelling, that through time led to the formation of the intra-crater bulges and, after compaction and sealing, to the widespread mound fields in their surroundings

Investigation of gender differences in stillbirths in Italian regions at the turn of the nineteenth century

AbstractData quality issues have hindered the analysis of the determinants of stillbirths in the years following Italian unification. By exploiting panel data techniques to take into account the possible effect of stillbirth misreporting, this paper investigates the relationship between seasonal agricultural workload and the number of male and female stillbirths in the Italian regions at the turn of the twentieth century (1883–1913). We found that although stillbirth rates were lower for females, agricultural workload seasonality had a more substantial effect for them. We suggest that this finding may be rationalised through the adaptive sex ratio adjustment hypothesis

In vitro antioxidant activity of aged extracts of some Italian Allium species

Antioxidant activity of fresh Allium sativum L. (garlic) is well known and is mainly due to unstable and irritating organosulphur compounds. Fresh garlic extracted over a prolonged period (up to 20 months) produces odourless aged garlic extract (AGE) containing stable and water soluble organosulphur compounds that prevent oxidative damage by scavenging free radicals. The aim of this study was to investigate the in vitro antioxidant activity of aged (up to 20 months) 15% hydroethanolic extracts of different parts (bulbs, bulblets, flower bulblets, flowers, and leaves) of three Allium spontaneous species which are endemic for Italian flora: Allium neapolitanum Cyr., Allium subhirsutum L., Allium roseum L. and to compare it with the in vitro antioxidant activity of aged 15% hydroethanolic extracts of bulbs and leaves of garlic. The antioxidant potential of aged extracts of all species has been evaluated using two different spectrophotometric assays: 2,2-diphenylpicrylhydrazyl (DPPH) test and the ferric reducing/antioxidant power (FRAP) assay. Furthermore the polyphenol content was determined. The aged extracts obtained from the leaves showed the best antioxidant activity, followed by flowers and then by bulbs in both used tests, while flower bulblets and bulblets exhibited lower results or no activity. The polyphenol content was generally directly correlated with antioxidant/antiradical activity. This study confirms the data obtained in previous researches, the wild-type species of Allium and in particular organs other than bulbs are more active and efficacious than garlic bulb. Surely leaves of these Allium spp. deserve special attentio

Mining Version Histories for Detecting Code Smells

Code smells are symptoms of poor design and implementation choices that may hinder code comprehension, and possibly increase change-and fault-proneness. While most of the detection techniques just rely on structural information, many code smells are intrinsically characterized by how code elements change over time. In this paper, we propose Historical Information for Smell deTection (HIST), an approach exploiting change history information to detect instances of five different code smells, namely Divergent Change, Shotgun Surgery, Parallel Inheritance, Blob, and Feature Envy. We evaluate HIST in two empirical studies. The first, conducted on 20 open source projects, aimed at assessing the accuracy of HIST in detecting instances of the code smells mentioned above. The results indicate that the precision of HIST ranges between 72 and 86 percent, and its recall ranges between 58 and 100 percent. Also, results of the first study indicate that HIST is able to identify code smells that cannot be identified by competitive approaches solely based on code analysis of a single system\u27s snapshot. Then, we conducted a second study aimed at investigating to what extent the code smells detected by HIST (and by competitive code analysis techniques) reflect developers\u27 perception of poor design and implementation choices. We involved 12 developers of four open source projects that recognized more than 75 percent of the code smell instances identified by HIST as actual design/implementation problems

prognostic health management of production systems new proposed approach and experimental evidences

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Thermal comfort prediction of aged industrial workers based on occupants' basal metabolic rate

The increasing workforce ageing brings benefits and challenges in industrial structu- res. Industries consider aged workers as essential resources thanks to their experience and skills. Conversely, the aged workers’ progressive functional and cognitive decline reduce their tolerance to industrial environmental conditions, negatively impacting performance. In particular, after age 30, there is a progressive inefficiency in the physiological response to temperature changes. Therefore, thermal discomfort conditions have a worse impact as the workers’ age increases. The Predicted Mean Vote (PMV) methodology is conventionally used to predict the human sensation of thermal comfort on a seven-point thermal sensation scale. Such methodology does not take account of progressive decline in thermoregulation capacity with age. This paper aims to fill this gap by proposing an analytic model for the prediction of thermal comfort. The Metabolic rate (M) parameter in the PMV equation is calculated from the Harris-Benedict equations revised by Mifflin and St Jeor (1990) for the Basal Metabolic Rate (BMR), including the age factor for a more accurate evaluation of the workers’ thermal sensation. The aim is to safeguard the aged workers’ health and well-being to enhance their performance during work

Mining Version Histories for Detecting Code Smells

Code smells are symptoms of poor design and implementation choices that may hinder code comprehension, and possibly increase change-and fault-proneness. While most of the detection techniques just rely on structural information, many code smells are intrinsically characterized by how code elements change over time. In this paper, we propose Historical Information for Smell deTection (HIST), an approach exploiting change history information to detect instances of five different code smells, namely Divergent Change, Shotgun Surgery, Parallel Inheritance, Blob, and Feature Envy. We evaluate HIST in two empirical studies. The first, conducted on 20 open source projects, aimed at assessing the accuracy of HIST in detecting instances of the code smells mentioned above. The results indicate that the precision of HIST ranges between 72 and 86 percent, and its recall ranges between 58 and 100 percent. Also, results of the first study indicate that HIST is able to identify code smells that cannot be identified by competitive approaches solely based on code analysis of a single system\u27s snapshot. Then, we conducted a second study aimed at investigating to what extent the code smells detected by HIST (and by competitive code analysis techniques) reflect developers\u27 perception of poor design and implementation choices. We involved 12 developers of four open source projects that recognized more than 75 percent of the code smell instances identified by HIST as actual design/implementation problems

Molecular Dynamics Characterization of the C2 Domain of Protein Kinase Cβ

Protein kinase C (PKC) isozymes comprise a family of related enzymes that play a central role in many intracellular eukaryotic signaling events. Isozyme specificity is mediated by association of each PKC isozyme with specific anchoring proteins, termed RACKs. The C2 domain of betaPKC contains at least part of the RACK-binding sites. Because the C2 domain contains also a RACK-like sequence (termed pseudo-RACK), it was proposed that this pseudo-RACK site mediates intramolecular interaction with one of the RACK-binding sites in the C2 domain itself, stabilizing the inactive conformation of betaPKC. BetaPKC depends on calcium for its activation, and the C2 domain contains the calcium-binding sites. The x-ray structure of the C2 domain of betaPKC shows that three Ca(2+) ions can be coordinated by two opposing loops at one end of the domain. Starting from this x-ray structure, we have performed molecular dynamics (MD) calculations on the C2 domain of betaPKC bound to three Ca(2+) ions, to two Ca(2+) ions, and in the Ca(2+)-free state, in order to analyze the effect of calcium on the RACK-binding sites and the pseudo-RACK sites, as well as on the loops that constitute the binding site for the Ca(2+) ions. The results show that calcium stabilizes the beta-sandwich structure of the C2 domain and thus affects two of the three RACK-binding sites within the C2 domain. Also, the interactions between the third RACK-binding site and the pseudo-RACK site are not notably modified by the removal of Ca(2+) ions. On that basis, we predict that the pseudo-RACK site within the C2 domain masks a RACK-binding site in another domain of betaPKC, possibly the V5 domain. Finally, the MD modeling shows that two Ca(2+) ions are able to interact with two molecules of O-phospho-l-serine. These data suggest that Ca(2+) ions may be directly involved in PKC binding to phosphatidylserine, an acidic lipid located exclusively on the cytoplasmic face of membranes, that is required for PKC activation