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Occupancy monitoring in smart buildings has great potential to improve their operational performance. One of the most common applications concerns the dynamic adaptation of indoor conditions according to the occupancy variation. However, other implementations are possible. Occupancy data could also enhance maintenance smart contracts management, especially if coupled with a contracts' management system as blockchain through which it is possible to achieve higher reliability and trust in transactions. In this article, a methodology to monitor occupancy data with a low-cost network, composed by a set of ultrasonic sensors, is presented. To ensure the collection of consistent data, different tests were performed for defining a convenient configuration for their installation. Following the proposed methodology, gathered data are processed and stored into a digital asset model associated with the building maintenance plan. Once a predefined threshold is reached, the system triggers a maintenance alert to the contractor to activate cleaning operations. The proposed approach enables an enhancement of the automation of maintenance management operations in a cost-effective manner. However, further validation trials are required to test the flexibility of its application in different space types. [ABSTRACT FROM AUTHOR]

The integration of Building Information Modelling (BIM) and Geographical Information Systems (GIS) is gaining momentum in digital built Asset Management (AM), and has the potential to improve information management operations and provide advantages in process control and delivery of quality AM services, along with underlying data management benefits through entire life cycle of an asset. Work has been carried out relating GeoBIM/AM to buildings as well as infrastructure assets, where the potential financial savings are extensive. While information form BIM maybe be sufficient for building-AM; for infrastructure AM a combination of GIS and BIM is required. Scientific literature relating to this topic has been growing in recent years and has now reached a point where a systematic analysis of current and potential uses of GeoBIM in AM for Infrastructure is possible. Three specific areas form part of the analysis – a review of BIM and Infrastructure AM and GIS and Infrastructure AM leads to a better understanding of current practice. Combining the two, a review of GeoBIM and Infrastructure AM allows the benefits of, and issues relating to, GeoBIM to be clearly identified, both at technical and operational levels. A set of 54 journal articles was selected for in-depth contents analysis according to the AM function addressed and the managed asset class. The analysis enabled the identification of three categories of issues and opportunities: data management, interoperability and integration and AM process and service management. The identified knowledge gaps, in turn, underpin problem definition for the next phases of research into GeoBIM for infrastructure AM. [ABSTRACT FROM AUTHOR]

Abstract.: We study the nonlinear response to an external force of an inertial tracer advected by a two-dimensional incompressible laminar flow and subject to thermal noise. In addition to the driving external field F, the main parameters in the system are the noise amplitude $D_{0}$ and the characteristic Stokes time $\tau$ of the tracer. The relation velocity vs. force shows interesting effects, such as negative differential mobility (NDM), namely a non-monotonic behavior of the tracer velocity as a function of the applied force, and absolute negative mobility (ANM), i.e. a net motion against the bias. By extensive numerical simulations, we investigate the phase chart in the parameter space of the model, $(\tau , D_{0})$ , identifying the regions where NDM, ANM and more common monotonic behaviors of the force-velocity curve are observed. Graphical abstract: [ABSTRACT FROM AUTHOR]

We briefly review some aspects of the anomalous diffusion, and its relevance in reactive systems. In particular we consider strong anomalous diffusion characterized by the moment behaviour (x (t)q) - tqv(q), where v(q) is a non constant function, and we discuss its consequences. Even in the apparently simple case ν (2) = 1/2, strong anomalous diffusion may correspond to non trivial features, such as non Gaussian probability distribution and peculiar scaling of large order moments. When a reactive term is added to a normal diffusion process, one has a propagating front with a constant velocity. The presence of anomalous diffusion by itself does not guarantee a changing in the front propagation scenario; a key factor to select linear in time or faster front propagation has been identified in the shape of the probability distribution tail in absence of reaction. In addition, we discuss the reaction spreading on graphs, underlying the major role of the connectivity properties of these structures, characterized by the connectivity dimension. [ABSTRACT FROM AUTHOR]

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways. [ABSTRACT FROM AUTHOR]

Autophagy is a catabolic process aimed at recycling cellular components and damaged organelles in response to diverse conditions of stress, such as nutrient deprivation, viral infection and genotoxic stress. A growing amount of evidence in recent years argues for oxidative stress acting as the converging point of these stimuli, with reactive oxygen species (ROS) and reactive nitrogen species (RNS) being among the main intracellular signal transducers sustaining autophagy. This review aims at providing novel insight into the regulatory pathways of autophagy in response to glucose and amino acid deprivation, as well as their tight interconnection with metabolic networks and redox homeostasis. The role of oxidative and nitrosative stress in autophagy is also discussed in the light of its being harmful for both cellular biomolecules and signal mediator through reversible posttranslational modifications of thiol-containing proteins. The redox-independent relationship between autophagy and antioxidant response, occurring through the p62/Keap1/Nrf2 pathway, is also addressed in order to provide a wide perspective upon the interconnection between autophagy and oxidative stress. Herein, we also attempt to afford an overview of the complex crosstalk between autophagy and DNA damage response (DDR), focusing on the main pathways activated upon ROS and RNS overproduction. Along these lines, the direct and indirect role of autophagy in DDR is dissected in depth. [ABSTRACT FROM AUTHOR]

Building condition assessment has become more and more important in the last years because it is essential at any time of buildings life. An assessment is absolutely necessary, for instance, in building takeovers to know what one is going to buy or it can be used to measure global service contracts success; similarly, to be aware of the building actual condition is important when planning maintenance. Condition assessment process results, in this research, are given by an efficiency index, made of an index assessing anomalies and two assessing degradation, pertaining to the whole building. Although the building assessment is obtained through a global index, which is computed from indexes assessing each building component degradation and anomalies so a deep knowledge of building condition is assured. In order to compute the degradation index, building components service life is compared to a Reference Service Life database. The two possible cases, either the service life of the component is smaller than the RSL or it is bigger, generate two different indexes here called D+ and D-. In order to compute the anomalies index building components anomalies are compared to a defined set of anomalies, which are categorized by typology, gravity of the damage and extension, and an index, here called A, measuring numbers and extensions of existing anomalies is created. Once building components have been assessed the information about their degradation (D+ and D-) and anomalies (A) of each component are grouped in building components families and then the three indexes of each family are grouped in indexes for the whole building. This index may be used in conjunction with another one assessing the building technical documents quality to reach a final index describing the whole building; both of them are supposed to be integrated in the building logbook. In this paper two case studies are presented in order to show how the building efficiency index works, how the intermediate results may be useful and to prove the effectiveness of the methodology. [ABSTRACT FROM AUTHOR]

Under stress conditions, pro-survival and pro-death processes are concomitantly activated and the final outcome depends on the complex crosstalk between these pathways. In most cases, autophagy functions as an early-induced cytoprotective response, favoring stress adaptation by removing damaged subcellular constituents. Moreover, several lines of evidence suggest that autophagy inactivation by the apoptotic machinery is a crucial event for cell death execution. Here we show that apoptotic stimuli induce a rapid decrease in the level of the autophagic factor Activating Molecule in Beclin1-Regulated Autophagy (Ambra1). Ambra1 degradation is prevented by concomitant inhibition of caspases and calpains. By both in vitro and in vivo approaches, we demonstrate that caspases are responsible for Ambra1 cleavage at the D482 site, whereas calpains are involved in complete Ambra1 degradation. Finally, we show that Ambra1 levels are critical for the rate of apoptosis induction. RNA interference-mediated Ambra1 downregulation further sensitizes cells to apoptotic stimuli, while Ambra1 overexpression and, more efficiently, a caspase non-cleavable mutant counteract cell death by prolonging autophagy induction. We conclude that Ambra1 is an important target of apoptotic proteases resulting in the dismantling of the autophagic machinery and the accomplishment of the cell death program. [ABSTRACT FROM AUTHOR]

Eukaryotic cells are equipped with an efficient quality control system to selectively eliminate misfolded and damaged proteins, and organelles. Abnormal polypeptides that escape from proteasome-dependent degradation and aggregate in the cytosol can be transported via microtubules to inclusion bodies called 'aggresomes', where misfolded proteins are confined and degraded by autophagy. Here, we show that Type 2 transglutaminase (TG2) knockout mice display impaired autophagy and accumulate ubiquitinated protein aggregates upon starvation. Furthermore, p62-dependent peroxisome degradation is also impaired in the absence of TG2. We also demonstrate that, under cellular stressful conditions, TG2 physically interacts with p62 and they are localized in cytosolic protein aggregates, which are then recruited into autophagosomes, where TG2 is degraded. Interestingly, the enzyme's crosslinking activity is activated during autophagy and its inhibition leads to the accumulation of ubiquitinated proteins. Taken together, these data indicate that the TG2 transamidating activity has an important role in the assembly of protein aggregates, as well as in the clearance of damaged organelles by macroautophagy. [ABSTRACT FROM AUTHOR]

Apaf1 is a key regulator of the mitochondrial intrinsic pathway of apoptosis, as it activates executioner caspases by forming the apoptotic machinery apoptosome. Its genetic regulation and its post-translational modification are crucial under the various conditions where apoptosis occurs. Here we describe Ku70/86, a mediator of non-homologous end-joining pathway of DNA repair, as a novel regulator of Apaf1 transcription. Through analysing different Apaf1 promoter mutants, we identified an element repressing the Apaf1 promoter. We demonstrated that Ku70/86 is a nuclear factor able to bind this repressing element and downregulating Apaf1 transcription. We also found that Ku70/86 interaction with Apaf1 promoter is dynamically modulated upon DNA damage. The effect of this binding is a downregulation of Apaf1 expression immediately following the damage to DNA; conversely, we observed Apaf1 upregulation and apoptosis activation when Ku70/86 unleashes the Apaf1-repressing element. Therefore, besides regulating DNA repair, our results suggest that Ku70/86 binds to the Apaf1 promoter and represses its activity. This may help to inhibit the apoptosome pathway of cell death and contribute to regulate cell survival. [ABSTRACT FROM AUTHOR]

Caspases are a family of cysteinyl aspartate-specific proteases that are highly conserved in multicellular organisms and function as central regulators of apoptosis. A member of this family, caspase-3, has been identified as a key mediator of apoptosis in neuronal cells. Recent studies in snail, fly and rat suggest that caspase-3 also functions as a regulatory molecule in neurogenesis and synaptic activity. In this study, in addition to providing an overview of the mechanism of caspase-3 activation, we review genetic and pharmacological studies of apoptotic and nonapoptotic functions of caspase-3 and discuss the regulatory mechanism of caspase-3 for executing nonapoptotic functions in the central nervous system. Knowledge of biochemical pathway(s) for nonapoptotic activation and modulation of caspase-3 has potential implications for the understanding of synaptic failure in the pathophysiology of neurological disorders. Fine-tuning of caspase-3 lays down a new challenge in identifying pharmacological avenues for treatment of many neurological disorders. [ABSTRACT FROM AUTHOR]

Study design:Retrospective study.Objectives:Efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord-injured patients (SCIPs) affected by chronic neurogenic bowel symptoms (NBSs).Setting:Neurourology Department. Primary to tertiary care.Methods:Retrospective non-blinded study without controls. Thirty-nine SCIPs were submitted to temporary stimulation for NBS. Permanent implantation was carried out if both their NBSs improved and the Wexner questionnaire scores were reduced by at least 50% during the first stage compared with that at baseline. Outcome measures included episodes of fecal incontinence and number of evacuations per week, as well as the Wexner score and the Short Form 36 (SF-36) Health Survey questionnaire.Results:Twenty-three SCIPs were submitted to definitive SNM, maintaining their clinical benefits after permanent implantation with a median follow-up of 38 months. The length of time since neurological diagnosis to SNM therapy represents the only factor related to the success of the implantation, P<0.05. In subjects with constipation (12), the median number of evacuations shifted from 1.65 to 4.98 per week, whereas the Wexner score changed from 19.91 to 6.82 in the final checkup with P<0.05. In subjects with fecal incontinence (11), the median number of episodes per week in the final follow-up was 1.32 compared with 4.55 pre-SNM. The general and mental health of both groups was measured with the SF-36 questionnaire and consistently showed statistical improvement (P<0.05).Anorectal manometry showed no important variation compared with baseline. There were no major complications.Conclusions:SNM therapy should be considered for the treatment of NBS for select patients with incomplete spinal cord injury when conservative treatments fail. [ABSTRACT FROM AUTHOR]

Background:To assess over the past year the sexuality of male patients with spinal-cord injury (SCI) over 50 years of age with spinal lesions of at least 20 years.Methods:Subjects were stratified in two groups: 44 individuals under 60 years and 55 individuals over 60 years. A detailed sexual anamnesis was taken for all, and the SF-36 Health Survey questionnaire was completed, with questions 13 and 14 concerning overall sexual life answered through the International Index of Erectile Function.Results:The younger group reached a median score of +50 for each domain of the SF-36; however, the differences between the two groups are not statistically relevant. The physical domain of the SF-36 showed a median score of 43.2 for the younger versus 41.1 for the older, whereas the mental domain showed 44.8 and 43.1, respectively. In the first group, 29/44 (65.9) individuals claimed erectile dysfunction versus 43/55 (78.1%) in the second, whereas 34/44 (77.2%) of the first group reported having sexual intercourse versus 13/55 (23.6%) with P<0.01 (χ2 test). In the 2nd, 29/55 (52.7%) individuals reported physical intimacy without sexual intercourse. For each group, the overall sexual satisfaction is statistically correlated to the duration of the relationship (linear progression test P<0.05).Conclusions:Median quality of life was high. Sexual intercourse is fundamental only for males of the first group. Most aging couples presented a different way of thinking about sex without the need for intercourse. Physicians should acquire knowledge about sexuality and aging in SCI patients.Sponsorship:This study was not sponsored.Spinal Cord (2008) 46, 679–683; doi:10.1038/sc.2008.37; published online 13 May 2008 [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs), such as spina bifida (SB) or exencephaly, are common congenital malformations leading to infant mortality or severe disability. The etiology of NTDs is multifactorial with a strong genetic component. More than 70 NTD mouse models have been reported, suggesting the involvement of distinct pathogenetic mechanisms, including faulty cell death regulation. In this review, we focus on the contribution of functional genomics in elucidating the role of apoptosis and autophagy genes in neurodevelopment. On the basis of compared phenotypical analysis, here we discuss the relative importance of a tuned control of both apoptosome-mediated cell death and basal autophagy for regulating the correct morphogenesis and cell number in developing central nervous system (CNS). The pharmacological modulation of genes involved in these processes may thus represent a novel strategy for interfering with the occurrence of NTDsCell Death and Differentiation (2008) 15, 1170–1177; doi:10.1038/cdd.2008.64; published online 2 May 2008 [ABSTRACT FROM AUTHOR]

One century after Einstein’s work, Brownian motion still remains both a fundamental open issue and a continuous source of inspiration for many areas of natural sciences. We first present a discussion about stochastic and deterministic approaches proposed in the literature to model the Brownian motion and more general diffusive behaviors. Then, we focus on the problems concerning the determination of the microscopic nature of diffusion by means of data analysis. Finally, we discuss the general conditions required for the onset of large scale diffusive motion. [ABSTRACT FROM AUTHOR]

Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1-/- embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1-/- NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1-/- NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-ßpeptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1-/- primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.Cell Death and Differentiation (2004) 11, 1179-1191. doi:10.1038/sj.cdd.4401476 Published online 16 July 2004 [ABSTRACT FROM AUTHOR]

We have generated rat monoclonal antibodies that specifically recognise caspase-2 from many species, including mouse, rat and humans. Using these antibodies, we have investigated caspase-2 expression, subcellular Iocalisation and processing. We demonstrate that caspase-2 is expressed in most tissues and cell types. Cell fractionation and immunohistochemistry experiments show that caspase-2 is found in the nuclear and cytosolic fractions, including a significant portion present in the Golgi complex. We found that caspase-2 is processed in response to many apoptotic stimuli but experiments with caspase-2 deficient mice demonstrated that it is not required for apoptosis of thymocytes or dorsal root ganglia (DRG) neurons in response to a variety of cytotoxic stimuli. Caspase-2 processing does not occur in thymocytes lacking Apaf-1 or caspase-9, suggesting that in this cell type, activation of caspase-2 occurs downstream of apoptosome formation. [ABSTRACT FROM AUTHOR]

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

The molecular characterization of the Caenorhabditis elegans cell death genes has been crucial in revealing some of the biochemical mechanisms underlying apoptosis in all animals. Four C. elegans genes, egl-1, ced-9, ced-4 and ced-3 are required for all somatic programmed cell death to occur. This genetic network is highly conserved during evolution. The pro-death gene egl-1 and the anti-death gene ced-9 have structural and functional similarities to the vertebrate Bcl2 gene family. The killer gene ced-3encodes a cystein-aspartate protease (caspase), which is the archetype of a family of conserved proteins known as effectors of apoptosis in mammals. Zou and collaborators reported the biochemical identification of an apoptotic protease activating factor (Apaf1), a human homolog of C. elegans CED-4, providing important clues to how CED-4 and its potential relatives could work. A number of proteins have been shown to interact with Apaf1 or to be determinant for its activity as an apoptotic adapter. The aim of this review is to provide an overview of the recent progress made in the field of developmental apoptosis by means of the murine Apaf1 targeted mutations. The central role of Apaf1 in the cell death machinery (apoptosome) and its involvement in different apoptotic pathways will also be discussed. [ABSTRACT FROM AUTHOR]

Adventitious buds were induced from in vitro culture of sunflower (Helianthus annuus L.) cotyledons. Four inbred lines (G1, G2, G3 and HA89), an open pollinated variety ('Argentario') and two hybrids with specific genetic markers were used. Cotyledons were cultured in vitro on MS medium (MURASHIGE and SKOOG 1962) containing various concentrations of kinetin and indole 3-acetic acid (IAA). The quantitative interactions between auxin and cytokinin, the age of the cotyledons and the 2,3,5-triiodobenzoic acid (TIBA) treatments have been found to influence shoot regeneration. The plantlets, after rooting, were successfully established on soil. Qualitative variation was noted in self- pollinated progeny of plants regenerated from culture of two inbreds. Chimerism in regenerated plants was indicated by sectoring of the genetic markers. Some culture-induced variant phenotypes were similar to known spontaneous mutation in sunflower but others have been not yet described. Preliminary data indicate that most of them may have single-gene recessive inheritance. [ABSTRACT FROM AUTHOR]

Indicates that the adapter molecule apoptotic protease activating factor 1 (Apaf1), reduced expression levels generate a mutant phenotype in adult brain and skeleton. Activation of the Apaf1 protein; Most striking feature of the apaf1/fog double heterozygous (DH) brain gross anatomy; Similarity of the anatomical and histological alterations for Apaf1/fogDH mutants with those described in fog/fog mutants.

Discusses the mediation of the transduction and amplification of the signal from mitochondria through the Apaf1. Identification of a fly cell death abnormal-4/Apaf1 homolog; Similarity of the mechanisms of apoptosome functions in flies and in worms and mammals; Existence of other Aparf1-like genes in vertebrates.

Atherosclerosis is a chronic inflammatory disorder of the large arteries and represents the primary cause of heart disease and stroke. The exact cause of atherosclerosis is not known. A variety of studies show that autophagy deficiency may be pro-atherogenic and the role of autophagy in smooth muscle cells, macrophages and endothelial cells has been investigated [1]. However, to date no studies addressed the effect of autophagy on leukocyte subsets playing a role in plaque formation and development. The presentproject aims to better clarify the role played by autophagy in lymphocyte homeostasis in human atherosclerotic plaques and in APOE-KO, a mouse model of atherogenesis [2]. In particular, we will investigate cell-autonomous autophagy in mouse Tconv/Tregfunctions, evaluate autophagy-driven T cell polarization in stabilizing atherosclerotic plaques in a mouse model mouse of atherosclerosis. The comprehension of the role of autophagy as a further mechanism underlying Treg induction and stability may open new therapeutic avenues for atherosclerosis. [ABSTRACT FROM AUTHOR]

We study the mobility and the diffusion coefficient of an inertial tracer advected by a two-dimensional incompressible laminar flow, in the presence of thermal noise and under the action of an external force. We show, with extensive numerical simulations, that the force-velocity relation for the tracer, in the nonlinear regime, displays complex and rich behaviors, including negative differential and absolute mobility. These effects rely upon a subtle coupling between inertia and applied force that induces the tracer to persist in particular regions of phase space with a velocity opposite to the force. The relevance of this coupling is revisited in the framework of nonequilibrium response theory, applying a generalized Einstein relation to our system. The possibility of experimental observation of these results is also discussed. [ABSTRACT FROM AUTHOR]