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This paper introduces technical solutions devised to support the Deployment Site - Regione Emilia Romagna (DS-RER) of the ACTIVAGE project. The ACTIVAGE project aims at promoting IoT (Internet of Things)-based solutions for Active and Healthy ageing. DS-RER focuses on improving continuity of care for older adults (65+) suffering from aftereffects of a stroke event. A Wireless Sensor Kit based on Wi-Fi connectivity was suitably engineered and realized to monitor behavioral aspects, possibly relevant to health and wellbeing assessment. This includes bed/rests patterns, toilet usage, room presence and many others. Besides hardware design and validation, cloud-based analytics services are introduced, suitable for automatic extraction of relevant information (trends and anomalies) from raw sensor data streams. The approach is general and applicable to a wider range of use cases; however, for readability’s sake, two simple cases are analyzed, related to bed and toilet usage patterns. In particular, a regression framework is introduced, suitable for detecting trends (long and short-term) and labeling anomalies. A methodology for assessing multi-modal daily behavioral profiles is introduced, based on unsupervised clustering techniques. The proposed framework has been successfully deployed at several real-users’ homes, allowing for its functional validation. Clinical effectiveness will be assessed instead through a Randomized Control Trial study, currently being carried out.

Artificial Intelligence in combination with the Internet of Medical Things enables remote healthcare services through networks of environmental and/or personal sensors. We present a remote healthcare service system which collects real-life data through an environmental sensor package, including binary motion, contact, pressure, and proximity sensors, installed at households of elderly people. Its aim is to keep the caregivers informed of subjects’ health-status progressive trajectory, and alert them of health-related anomalies to enable objective on-demand healthcare service delivery at scale. The system was deployed in 19 households inhabited by an elderly person with post-stroke condition in the Emilia–Romagna region in Italy, with maximal and median observation durations of 98 and 55 weeks. Among these households, 17 were multi-occupancy residences, while the other 2 housed elderly patients living alone. Subjects’ daily behavioral diaries were extracted and registered from raw sensor signals, using rule-based data pre-processing and unsupervised algorithms. Personal behavioral habits were identified and compared to typical patterns reported in behavioral science, as a quality-of-life indicator. We consider the activity patterns extracted across all users as a dictionary, and represent each patient’s behavior as a ‘Bag of Words’, based on which patients can be categorized into sub-groups for precision cohort treatment. Longitudinal trends of the behavioral progressive trajectory and sudden abnormalities of a patient were detected and reported to care providers. Due to the sparse sensor setting and the multi-occupancy living condition, the sleep profile was used as the main indicator in our system. Experimental results demonstrate the ability to report on subjects’ daily activity pattern in terms of sleep, outing, visiting, and health-status trajectories, as well as predicting/detecting 75% hospitalization sessions up to 11 days in advance. 65% of the alerts were confirmed to be semantically meaningful by the users. Furthermore, reduced social interaction (outing and visiting), and lower sleep quality could be observed during the COVID-19 lockdown period across the cohort.

Entry of herpes simplex virus (HSV) 1 into cells requires the interaction of HSV gD with herpesvirus entry mediator or nectin 1 receptors, and fusion with cell membrane mediated by the fusion glycoproteins gB, gH, and gL. We report that the gD ectodomain in soluble form (amino acids 1-305) was sufficient to rescue the infectivity of a gD-null HSV mutant, indicating that gD does not need to be anchored to the virion envelope to mediate entry. Entry mediated by soluble gD required, in addition to the receptor-binding sites contained within residues 1-250, a discrete downstream portion (amino acids 261-305), located proximal to the transmembrane segment in full-length gD. We named it as profusion domain. The pro-fusion domain was required for entry mediated by virion-bound gD, because its substitution with the corresponding region of CD8 failed to complement the infectivity of gD-/+ HSV. Furthermore, a receptor-negative gD ( gDΔ 6-259) inhibited virus infectivity when coexpressed with wild-type gD; i.e., it acted as a dominant-negative gD mutant. The pro-fusion domain is proline-rich, which is characteristic of regions involved in protein-protein interactions. P291L-P292A substitutions diminished the gD capacity to complement gD-/+ HSV infectivity. We propose that gD forms a tripartite complex with its receptor and, by way of the proline-rich pro-fusion domain, with the fusion glycoproteins, or with one of them. The tripartite complex would serve to recruit/activate the fusion glycoproteins and bring them from a fusion-inactive to a fusion-active state, such that they execute fusion of the virion envelope with cell membrane.

The herpesvirus entry mediator C (HveC), previously known as poliovirus receptor-related protein 1 (PRR1), and the herpesvirus Ig-like receptor (HIgR) are the bona fide receptors employed by herpes simplex virus-1 and -2 (HSV-1 and -2) for entry into the human cell lines most frequently used in HSV studies. They share an identical ectodomain made of one V and two C2 domains and differ in transmembrane and cytoplasmic regions. Expression of their mRNA in the human nervous system suggests possible usage of these receptors in humans in the path of neuron infection by HSV. Glycoprotein D (gD) is the virion component that mediates HSV-1 entry into cells by interaction with cellular receptors. We report on the identification of the V domain of HIgR/PRR1 as a major functional region in HSV-1 entry by several approaches. First, the epitope recognized by mAb R1.302 to HIgR/PRR1, capable of inhibiting infection, was mapped to the V domain. Second, a soluble form of HIgR/PRR1 consisting of the single V domain competed with cell-bound full-length receptor and blocked virion infectivity. Third, the V domain was sufficient to mediate HSV entry, as an engineered form of PRR1 in which the two C2 domains were deleted and the V domain was retained and fused to its transmembrane and cytoplasmic regions was still able to confer susceptibility, although at reduced efficiency relative to full-length receptor. Consistently, transfer of the V domain of HIgR/PRR1 to a functionally inactive structural homologue generated a chimeric receptor with virus-entry activity. Finally, the single V domain was sufficient for in vitro physical interaction with gD. The in vitro binding was specific as it was competed both by antibodies to the receptor and by a mAb to gD with potent neutralizing activity for HSV-1 infectivity.

The full-length cDNA of the murine homolog of human nectin1 δ (mNerctin 1δ ), also known as human poliovirus receptor related 1 (PRR1) or herpesvirus entry mediator C, was cloned and showed a >90% identity with its human counterpart. mNectin1 δ is expressed in some murine cell lines, exemplified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabies virus (PrV), and bovine herpesvirus 1. A soluble form of the mediator blocked infectivi in mNectin1 δ and human nectin1 δ (hNectin1 δ )-expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block infectivity relative to soluble hNectin1 suggest that the target of the two molecules is not identical. Entry of HSV, but not PrV, was blocked by soluble mNectin1 δ in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1 δ failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1 δ and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1 δ fails to be sequestered by HSV gD. We conclude that mNectin1 δ serves as a species-nonspecific mediator for entry of the human and animal α herpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.

An extended array of cell surface molecules serve as receptors for HSV entry into cells. In addition to the heparan sulphate glycosaminoglycans, which mediate the attachment of virion to cells, HSV requires an entry receptor. The repertoire of entry receptors into human cells includes molecules from three structurally unrelated molecular families. They are (i) HveA (herpesvirus entry mediator A), (ii) members of the nectin family, (iii) 3‐O‐sulphated heparan sulphate. The molecules have different attributes and play potentially different roles in HSV infection and spread to human tissues. All the human entry receptors interact physically with the virion envelope glycoprotein D (gD). (i) HveA is a member of the TNF‐receptor family. It mediates entry of a restricted range of HSV strains. Its expression is restricted to few lineages (e.g. T‐lymphocytes). (ii) The human nectin1α (HIgR), nectin1δ (PRR1‐HveC), and the nectin2α (PRR2α‐HveB) and nectin2δ (PRR2δ) belong to the immunoglobulin superfamily. They are homologues of the poliovirus receptor (CD155), with which they share the overall structure of the ectodomain. The human nectin1α‐δ are broadly expressed in cell lines of different lineages, are expressed in human tissue targets of HSV infection, serve as receptors for all HSV‐1 and HSV‐2 strains tested and mediate entry not only of free virions, but also cell‐to‐cell spread of virus. (iii) The 3‐O‐sulphated heparan sulphate is expressed in some selected human cell lines (e.g. endothelial and mast cells) and human tissues, and mediates entry of HSV‐1, but not HSV‐2. The human nectin2α and nectin2δ serve as receptors for a narrow range of viruses. A characteristic of the human nectin1α‐δ is the promiscuous species non‐specific receptor activity towards the animal alphaherpesviruses, pseudorabies virus (PrV) and bovine herpesvirus 1 (BHV‐1). By contrast with the human nectin1δ, its murine homologue (mNectin1δ) does not bind gD at detectable level, yet it mediates entry of HSV, as well as of PrV and BHV‐1. This provides the first example of a mediator of HSV entry independent of a detectable interaction with gD. Copyright © 2000 John Wiley & Sons, Ltd.

IoT technologies generate intelligence and connectivity and develop knowledge to be used in the decision-making process. However, research that uses big data through global interconnected infrastructures, such as the ‘Internet of Things’ (IoT) for Active and Healthy Ageing (AHA), is fraught with several ethical concerns. A large-scale application of IoT operating in diverse piloting contexts and case studies needs to be orchestrated by a robust framework to guide ethical and sustainable decision making in respect to data management of AHA and IoT based solutions. The main objective of the current article is to present the successful completion of a collaborative multiscale research work, which addressed the complicated exercise of ethical decision making in IoT smart ecosystems for older adults. Our results reveal that among the strong enablers of the proposed ethical decision support model were the participatory and deliberative procedures complemented by a set of regulatory and non-regulatory tools to operationalize core ethical values such as transparency, trust, and fairness in real care settings for older adults and their caregivers.

Entry of herpes simplex virus (HSV) 1 into cells requires the interaction of HSV gD with herpesvirus entry mediator or nectin1 receptors, and fusion with cell membrane mediated by the fusion glycoproteins gB, gH, and gL. We report that the gD ectodomain in soluble form (amino acids 1-305) was sufficient to rescue the infectivity of a gD-null HSV mutant, indicating that gD does not need to be anchored to the virion envelope to mediate entry. Entry mediated by soluble gD required, in addition to the receptor-binding sites contained within residues 1-250, a discrete downstream portion (amino acids 261-305), located proximal to the transmembrane segment in full-length gD. We named it as profusion domain. The pro-fusion domain was required for entry mediated by virion-bound gD, because its substitution with the corresponding region of CD8 failed to complement the infectivity of gD-/+ HSV. Furthermore, a receptor-negative gD (gD{Delta}6-259) inhibited virus infectivity when coexpressed with wild-type gD; i.e., it acted as a dominant-negative gD mutant. The pro-fusion domain is proline-rich, which is characteristic of regions involved in protein-protein interactions. P291L-P292A substitutions diminished the gD capacity to complement gD-/+ HSV infectivity. We propose that gD forms a tripartite complex with its receptor and, by way of the proline-rich pro-fusion domain, with the fusion glycoproteins, or with one of them. The tripartite complex would serve to recruit/activate the fusion glycoproteins and bring them from a fusion-inactive to a fusion-active state, such that they execute fusion of the virion envelope with cell membrane. [PUBLICATION ABSTRACT]

Setting a record for the University, 13 students and alumni of the College of Liberal Arts and Sciences will travel to countries around the globe to pursue teaching assistantships or conduct research through the 2014-2015 Fulbright U.S. Student Grant.

The sophomore residence hall joins four other campus buildings--the Law School, Driscoll Hall, Sheehan Hall and Sullivan Hall--that meet LEED standards based on sustainable sites, water efficiency, energy and atmosphere, materials and resources, indoor environmental quality and innovation in design, according to the University's sustainability web tab. Schwarz described the residence hall's other sustainability features, which include vacancy sensors that automatically shut lights off in an empty room, low flow shower heads, high instillation windows that prevent drafts, lighter paint that increases natural lighting and high efficiency lighting systems that use less energy.