Design and technical evaluation of an enhanced location-awareness service enabler for spatial disorientation management of elderly with mild cognitive impairment

The progressive ageing of population has turned the mild cognitive impairment (MCI) into a prevalent disease suffered by elderly. Consequently, the spatial disorientation has become a significant problem for older people and their caregivers. The ambient-assisted living applications are offering location-based services for empowering elderly to go outside and encouraging a greater independence. Therefore, this paper describes the design and technical evaluation of a location-awareness service enabler aimed at supporting and managing probable wandering situations of a person with MCI. Through the presence capabilities of the IP multimedia subsystem (IMS) architecture, the service will alert patient's contacts if a hazardous situation is detected depending on his location. Furthermore, information about the older person's security areas has been included in the user profile managed by IMS. In doing so, the service enabler introduced contribute to “context-awareness” paradigm allowing the adaptation and personalization of services depending on user's context and specific conditions or preferences.

The chair of food Banks UPM as a tool of raising awareness and promoting a culture of rational food comsumption

The Chair of Food Banks UPM arises from a cooperation agreement between the Spanish Federation of Food Banks (FESBAL) and the Technical University of Madrid (UPM), with the aim of raising awareness and promoting rational food consumption to avoid food waste, through activities of training, transfer of knowledge and promotion of I+D+i. The aim of this paper is to reflect on the activities carried out during the first year in order to obtain learning lessons and improve the management of activities and resources.

Context-awareness in task automation services by distributed event processing

Everybody has to coordinate several tasks everyday, usually in a manual manner. Recently, the concept of Task Automation Services has been introduced to automate and personalize the task coordination problem. Several user centered platforms and applications have arisen in the last years, that let their users configure their very own automations based on third party services. In this paper, we propose a new system architecture for Task Automation Services in a heterogeneous mobile, smart devices, and cloud services environment. Our architecture is based on the novel idea to employ distributed Complex Event Processing to implement innovative mixed execution profiles. The major advantage of the approach is its ability to incorporate context-awareness and real-time coordination in Task Automation Services.

Utilizing the Internet of Things to promote energy awareness and efficiency at discrete production processes: Practices and methodology

El actual contexto de fabricación, con incrementos en los precios de la energía, una creciente preocupación medioambiental y cambios continuos en los comportamientos de los consumidores, fomenta que los responsables prioricen la fabricación respetuosa con el medioambiente. El paradigma del Internet de las Cosas (IoT) promete incrementar la visibilidad y la atención prestada al consumo de energía gracias tanto a sensores como a medidores inteligentes en los niveles de máquina y de línea de producción. En consecuencia es posible y sencillo obtener datos de consumo de energía en tiempo real proveniente de los procesos de fabricación, pero además es posible analizarlos para incrementar su importancia en la toma de decisiones. Esta tesis pretende investigar cómo utilizar la adopción del Internet de las Cosas en el nivel de planta de producción, en procesos discretos, para incrementar la capacidad de uso de la información proveniente tanto de la energía como de la eficiencia energética. Para alcanzar este objetivo general, la investigación se ha dividido en cuatro sub-objetivos y la misma se ha desarrollado a lo largo de cuatro fases principales (en adelante estudios). El primer estudio de esta tesis, que se apoya sobre una revisión bibliográfica comprehensiva y sobre las aportaciones de expertos, define prácticas de gestión de la producción que son energéticamente eficientes y que se apoyan de un modo preeminente en la tecnología IoT. Este primer estudio también detalla los beneficios esperables al adoptar estas prácticas de gestión. Además, propugna un marco de referencia para permitir la integración de los datos que sobre el consumo energético se obtienen en el marco de las plataformas y sistemas de información de la compañía. Esto se lleva a cabo con el objetivo último de remarcar cómo estos datos pueden ser utilizados para apalancar decisiones en los niveles de procesos tanto tácticos como operativos. Segundo, considerando los precios de la energía como variables en el mercado intradiario y la disponibilidad de información detallada sobre el estado de las máquinas desde el punto de vista de consumo energético, el segundo estudio propone un modelo matemático para minimizar los costes del consumo de energía para la programación de asignaciones de una única máquina que deba atender a varios procesos de producción. Este modelo permite la toma de decisiones en el nivel de máquina para determinar los instantes de lanzamiento de cada trabajo de producción, los tiempos muertos, cuándo la máquina debe ser puesta en un estado de apagada, el momento adecuado para rearrancar, y para pararse, etc. Así, este modelo habilita al responsable de producción de implementar el esquema de producción menos costoso para cada turno de producción. En el tercer estudio esta investigación proporciona una metodología para ayudar a los responsables a implementar IoT en el nivel de los sistemas productivos. Se incluye un análisis del estado en que se encuentran los sistemas de gestión de energía y de producción en la factoría, así como también se proporcionan recomendaciones sobre procedimientos para implementar IoT para capturar y analizar los datos de consumo. Esta metodología ha sido validada en un estudio piloto, donde algunos indicadores clave de rendimiento (KPIs) han sido empleados para determinar la eficiencia energética. En el cuarto estudio el objetivo es introducir una vía para obtener visibilidad y relevancia a diferentes niveles de la energía consumida en los procesos de producción. El método propuesto permite que las factorías con procesos de producción discretos puedan determinar la energía consumida, el CO2 emitido o el coste de la energía consumida ya sea en cualquiera de los niveles: operación, producto o la orden de fabricación completa, siempre considerando las diferentes fuentes de energía y las fluctuaciones en los precios de la misma. Los resultados muestran que decisiones y prácticas de gestión para conseguir sistemas de producción energéticamente eficientes son posibles en virtud del Internet de las Cosas. También, con los resultados de esta tesis los responsables de la gestión energética en las compañías pueden plantearse una aproximación a la utilización del IoT desde un punto de vista de la obtención de beneficios, abordando aquellas prácticas de gestión energética que se encuentran más próximas al nivel de madurez de la factoría, a sus objetivos, al tipo de producción que desarrolla, etc. Así mismo esta tesis muestra que es posible obtener reducciones significativas de coste simplemente evitando los períodos de pico diario en el precio de la misma. Además la tesis permite identificar cómo el nivel de monitorización del consumo energético (es decir al nivel de máquina), el intervalo temporal, y el nivel del análisis de los datos son factores determinantes a la hora de localizar oportunidades para mejorar la eficiencia energética. Adicionalmente, la integración de datos de consumo energético en tiempo real con datos de producción (cuando existen altos niveles de estandarización en los procesos productivos y sus datos) es esencial para permitir que las factorías detallen la energía efectivamente consumida, su coste y CO2 emitido durante la producción de un producto o componente. Esto permite obtener una valiosa información a los gestores en el nivel decisor de la factoría así como a los consumidores y reguladores. ABSTRACT In today‘s manufacturing scenario, rising energy prices, increasing ecological awareness, and changing consumer behaviors are driving decision makers to prioritize green manufacturing. The Internet of Things (IoT) paradigm promises to increase the visibility and awareness of energy consumption, thanks to smart sensors and smart meters at the machine and production line level. Consequently, real-time energy consumption data from the manufacturing processes can be easily collected and then analyzed, to improve energy-aware decision-making. This thesis aims to investigate how to utilize the adoption of the Internet of Things at shop floor level to increase energy–awareness and the energy efficiency of discrete production processes. In order to achieve the main research goal, the research is divided into four sub-objectives, and is accomplished during four main phases (i.e., studies). In the first study, by relying on a comprehensive literature review and on experts‘ insights, the thesis defines energy-efficient production management practices that are enhanced and enabled by IoT technology. The first study also explains the benefits that can be obtained by adopting such management practices. Furthermore, it presents a framework to support the integration of gathered energy data into a company‘s information technology tools and platforms, which is done with the ultimate goal of highlighting how operational and tactical decision-making processes could leverage such data in order to improve energy efficiency. Considering the variable energy prices in one day, along with the availability of detailed machine status energy data, the second study proposes a mathematical model to minimize energy consumption costs for single machine production scheduling during production processes. This model works by making decisions at the machine level to determine the launch times for job processing, idle time, when the machine must be shut down, ―turning on‖ time, and ―turning off‖ time. This model enables the operations manager to implement the least expensive production schedule during a production shift. In the third study, the research provides a methodology to help managers implement the IoT at the production system level; it includes an analysis of current energy management and production systems at the factory, and recommends procedures for implementing the IoT to collect and analyze energy data. The methodology has been validated by a pilot study, where energy KPIs have been used to evaluate energy efficiency. In the fourth study, the goal is to introduce a way to achieve multi-level awareness of the energy consumed during production processes. The proposed method enables discrete factories to specify energy consumption, CO2 emissions, and the cost of the energy consumed at operation, production and order levels, while considering energy sources and fluctuations in energy prices. The results show that energy-efficient production management practices and decisions can be enhanced and enabled by the IoT. With the outcomes of the thesis, energy managers can approach the IoT adoption in a benefit-driven way, by addressing energy management practices that are close to the maturity level of the factory, target, production type, etc. The thesis also shows that significant reductions in energy costs can be achieved by avoiding high-energy price periods in a day. Furthermore, the thesis determines the level of monitoring energy consumption (i.e., machine level), the interval time, and the level of energy data analysis, which are all important factors involved in finding opportunities to improve energy efficiency. Eventually, integrating real-time energy data with production data (when there are high levels of production process standardization data) is essential to enable factories to specify the amount and cost of energy consumed, as well as the CO2 emitted while producing a product, providing valuable information to decision makers at the factory level as well as to consumers and regulators.

Alternative neural circuitry that might be impaired in the development of Alzheimer disease

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as A? or tau protein present in different areas of the brain could be important.

Mutually compensatory mutations during evolution of the tetramerization domain of tumor suppressor p53 lead to impaired hetero-oligomerization

We have measured the stability and stoichiometry of variants of the human p53 tetramerization domain to assess the effects of mutation on homo- and hetero-oligomerization. The residues chosen for mutation were those in the hydrophobic core that we had previously found to be critical for its stability but are not conserved in human p73 or p51 or in p53-related proteins from invertebrates or vertebrates. The mutations introduced were either single natural mutations or combinations of mutations present in p53-like proteins from different species. Most of the mutations were substantially destabilizing when introduced singly. The introduction of multiple mutations led to two opposite effects: some combinations of mutations that have occurred during the evolution of the hydrophobic core of the domain in p53-like proteins had additive destabilizing effects, whereas other naturally occurring combinations of mutations had little or no net effect on the stability, there being mutually compensating effects of up to 9.5 kcal/mol of tetramer. The triple mutant L332V/F341L/L344I, whose hydrophobic core represents that of the chicken p53 domain, was nearly as stable as the human domain but had impaired hetero-oligomerization with it. Thus, engineering of a functional p53 variant with a reduced capacity to hetero-oligomerize with wild-type human p53 can be achieved without any impairment in the stability and subunit affinity of the engineered homo-oligomer.

Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein

CREB, the cAMP response element binding protein, is a key transcriptional regulator of a large number of genes containing a CRE consensus sequence in their upstream regulatory regions. Mice with a hypomorphic allele of CREB that leads to a loss of the CREBα and Δ isoforms and to an overexpression of the CREBβ isoform are viable. Herein we report the generation of CREB null mice, which have all functional isoforms (CREBα, β, and Δ) inactivated. In contrast to the CREBαΔ mice, CREB null mice are smaller than their littermates and die immediately after birth from respiratory distress. In brain, a strong reduction in the corpus callosum and the anterior commissures is observed. Furthermore, CREB null mice have an impaired fetal T cell development of the αβ lineage, which is not affected in CREBαΔ mice on embryonic day 18.5. Overall thymic cellularity in CREB null mice is severely reduced affecting all developmental stages of the αβ T cell lineage. In contrast γδ T cell differentiation is normal in CREB mutant mice.

Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation : a systematic review and economic evaluation

Peer reviewed

Isolation of quelling-defective (qde) mutants impaired in posttranscriptional transgene-induced gene silencing in Neurospora crassa

We report the isolation of 15 Neurospora crassa mutants defective in “quelling” or transgene-induced gene silencing. These quelling-defective mutants (qde) belonging to three complementation groups have provided insights into the mechanism of posttranscriptional gene silencing in N. crassa. The recessive nature of the qde mutations indicates that the encoded gene products act in trans. We show that when qde genes are mutated in a transgenic-induced silenced strain containing many copies of the transgene, the expression of the endogenous gene is maintained despite the presence of transgene sense RNA, the molecule proposed to trigger quelling. Moreover, the qde mutants failed to show quelling when tested with another gene, suggesting that they may be universally defective in transgene-induced gene silencing. As such, qde genes may be involved in sensing aberrant sense RNA and/or targeting/degrading the native mRNA. The qde mutations may be used to isolate the genes encoding the first components of the quelling mechanism. Moreover, these quelling mutants may be important in applied and basic research for the creation of strains able to overexpress a transgene.

Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+ cytotoxic T lymphocyte responses

The specific mechanisms underlying the varied susceptibility of HIV-infected (HIV+) individuals to opportunistic infections (OI) are still incompletely understood. One hypothesis is that quantitative differences in specific T cell responses to a colonizing organism determine the development of an AIDS-defining OI. We evaluated this hypothesis for herpes simplex virus (HSV) infection, a common OI in HIV+ patients. Using limiting dilution analyses, the frequency of HSV-specific CD8+ cytotoxic T lymphocyte precursors (pCTL) and proliferative precursors were quantitated in peripheral blood mononuclear cells from 20 patients coinfected with HIV and HSV-2. The frequency of HSV-specific CD8+ pCTL in HSV+HIV+ individuals was significantly lower than in HSV+HIV− individuals (1 in 77,000 vs. 1 in 6,000, P = .0005) and was not different than in HSV-HIV− individuals (1 in 100,000, P = .24). HIV+ patients who suffered more severe genital herpes recurrences had significantly lower HSV-specific CD8+ pCTL frequencies than those patients with mild recurrences (1 in 170,000 vs. 1 in 26,000, P = .03). In contrast, no significant difference was seen in proliferative precursor frequencies between those patients with mild vs. severe genital herpes (1 in 3,800 vs. 1 in 6,600, P > .5). Quantitative differences in pCTL frequency to HSV appear to be the most important host factor influencing the frequency and severity of HSV reactivation in HIV+ patients. Studies to reconstitute such immunity, especially in people with acyclovir-resistant HSV, appear warranted.

Impaired long-term potentiation induction in dentate gyrus of calretinin-deficient mice

Calretinin (Cr) is a Ca2+ binding protein present in various populations of neurons distributed in the central and peripheral nervous systems. We have generated Cr-deficient (Cr−/−) mice by gene targeting and have investigated the associated phenotype. Cr−/− mice were viable, and a large number of morphological, biochemical, and behavioral parameters were found unaffected. In the normal mouse hippocampus, Cr is expressed in a widely distributed subset of GABAergic interneurons and in hilar mossy cells of the dentate gyrus. Because both types of cells are part of local pathways innervating dentate granule cells and/or pyramidal neurons, we have explored in Cr−/− mice the synaptic transmission between the perforant pathway and granule cells and at the Schaffer commissural input to CA1 pyramidal neurons. Cr−/− mice showed no alteration in basal synaptic transmission, but long-term potentiation (LTP) was impaired in the dentate gyrus. Normal LTP could be restored in the presence of the GABAA receptor antagonist bicuculline, suggesting that in Cr−/− dentate gyrus an excess of γ-aminobutyric acid (GABA) release interferes with LTP induction. Synaptic transmission and LTP were normal in CA1 area, which contains only few Cr-positive GABAergic interneurons. Cr−/− mice performed normally in spatial memory task. These results suggest that expression of Cr contributes to the control of synaptic plasticity in mouse dentate gyrus by indirectly regulating the activity of GABAergic interneurons, and that Cr−/− mice represent a useful tool to understand the role of dentate LTP in learning and memory.

Constitutive and impaired signaling of leptin receptors containing the Gln → Pro extracellular domain fatty mutation

Leptin (OB), an adipocyte-secreted circulating hormone, and its receptor (OB-R) are key components of an endocrine loop that regulates mammalian body weight. In this report we have analyzed signal transduction activities of OB-R containing the fatty mutation [OB-R(fa)], a single amino acid substitution at position 269 (Gln → Pro) in the OB-R extracellular domain that results in the obese phenotype of the fatty rat. We find that this mutant receptor exhibits both ligand-independent transcriptional activation via interleukin 6 and hematopoietin receptor response elements and ligand-independent activation of signal transducer and activator of transcription (STAT) proteins 1 and 3. However, OB-R(fa) is unable to constitutively activate STAT5B and is highly impaired for ligand induced activation of STAT5B compared with OB-R(wt). Introduction of the fatty mutation into a OB-R/G-CSF-R chimera generates a receptor with constitutive character that is similar but distinct from that of OB-R(fa). Constitutive mutant OB-R(fa) receptor signaling is repressed by coexpression of OB-R(wt). The implications of an extracellular domain amino acid substitution generating a cytokine receptor with a partially constitutive phenotype are discussed both in terms of the mechanism of OB-R triggering and the biology of the fatty rat.

Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice

The tetraspanin CD81 is ubiquitously expressed and associated with CD19 on B lymphocytes and with CD4 and CD8 on T lymphocytes. Analysis of mice with disrupted CD81 gene reveals normal T cells but a distinct abnormality in B cells consisting of decreased expression of CD19 and severe reduction in peritoneal B-1 cells. CD81-deficient B cells responded normally to surface IgM crosslinking, but had severely impaired calcium influx following CD19 engagement. CD81-deficient mice had increased serum IgM and IgA and an exaggerated antibody response to the type II T independent antigen TNP-Ficoll. These results suggest that CD81 is important for CD19 signaling and B cell function.

Long-term but not short-term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule-deficient mice

Cell adhesion molecules (CAMs) are known to be involved in a variety of developmental processes that play key roles in the establishment of synaptic connectivity during embryonic development, but recent evidence implicates the same molecules in synaptic plasticity of the adult. In the present study, we have used neural CAM (NCAM)-deficient mice, which have learning and behavioral deficits, to evaluate NCAM function in the hippocampal mossy fiber system. Morphological studies demonstrated that fasciculation and laminar growth of mossy fibers were strongly affected, leading to innervation of CA3 pyramidal cells at ectopic sites, whereas individual mossy fiber boutons appeared normal. Electrophysiological recordings performed in hippocampal slice preparations revealed that both basal synaptic transmission and two forms of short-term plasticity, i.e., paired-pulse facilitation and frequency facilitation, were normal in mice lacking all forms of NCAM. However, long-term potentiation of glutamatergic excitatory synapses after brief trains of repetitive stimulation was abolished. Taken together, these results strongly suggest that in the hippocampal mossy fiber system, NCAM is essential both for correct axonal growth and synaptogenesis and for long-term changes in synaptic strength.

Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.