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  1. Article ; Online: Detection of Anomalies in Daily Activities Using Data from Smart Meters.

    Hernández, Álvaro / Nieto, Rubén / de Diego-Otón, Laura / Pérez-Rubio, María Carmen / Villadangos-Carrizo, José M / Pizarro, Daniel / Ureña, Jesús

    Sensors (Basel, Switzerland)

    2024  Volume 24, Issue 2

    Abstract: The massive deployment of smart meters in most Western countries in recent decades has allowed the creation and development of a significant variety of applications, mainly related to efficient energy management. The information provided about energy ... ...

    Abstract The massive deployment of smart meters in most Western countries in recent decades has allowed the creation and development of a significant variety of applications, mainly related to efficient energy management. The information provided about energy consumption has also been dedicated to the areas of social work and health. In this context, smart meters are considered single-point non-intrusive sensors that might be used to monitor the behaviour and activity patterns of people living in a household. This work describes the design of a short-term behavioural alarm generator based on the processing of energy consumption data coming from a commercial smart meter. The device captured data from a household for a period of six months, thus providing the consumption disaggregated per appliance at an interval of one hour. These data were used to train different intelligent systems, capable of estimating the predicted consumption for the next one-hour interval. Four different approaches have been considered and compared when designing the prediction system: a recurrent neural network, a convolutional neural network, a random forest, and a decision tree. By statistically analysing these predictions and the actual final energy consumption measurements, anomalies can be detected in the undertaking of three different daily activities: sleeping, breakfast, and lunch. The recurrent neural network achieves an F1-score of 0.8 in the detection of these anomalies for the household under analysis, outperforming other approaches. The proposal might be applied to the generation of a short-term alarm, which can be involved in future deployments and developments in the field of ambient assisted living.
    MeSH term(s) Humans ; Ambient Intelligence ; Intelligence ; Neural Networks, Computer ; Sleep
    Language English
    Publishing date 2024-01-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2052857-7
    ISSN 1424-8220 ; 1424-8220
    ISSN (online) 1424-8220
    ISSN 1424-8220
    DOI 10.3390/s24020515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Potent Immunomodulators Developed from an Unstable Bacterial Metabolite of Vitamin B2 Biosynthesis.

    Mak, Jeffrey Y W / Rivero, Ryan J D / Hoang, Huy N / Lim, Xin Yi / Deng, Jieru / McWilliam, Hamish E G / Villadangos, Jose A / McCluskey, James / Corbett, Alexandra J / Fairlie, David P

    Angewandte Chemie (International ed. in English)

    2024  , Page(s) e202400632

    Abstract: Bacterial synthesis of vitamin B2 generates a by-product, 5-(2-oxopropylideneamino)-d-ribityl-aminouracil (5-OP-RU), with potent immunological properties in mammals, but rapid inactivation in water limits practical uses. This natural product covalently ... ...

    Abstract Bacterial synthesis of vitamin B2 generates a by-product, 5-(2-oxopropylideneamino)-d-ribityl-aminouracil (5-OP-RU), with potent immunological properties in mammals, but rapid inactivation in water limits practical uses. This natural product covalently bonds to immunological protein MR1 in antigen presenting cells (APCs), enabling MR1 to traffic to the cell surface, where it interacts with T cell receptors (TCRs) on mucosal associated invariant T lymphocytes (MAIT cells), activating their immunological and antimicrobial properties. Here, we develop several new series of water-stable compounds tailored for powerful and distinctive immunological functions. We report their water stability, capacity to bind MR1 and traffic it to the cell surface (EC50 17 nM), potent activation (EC50 56 pM) or inhibition (IC50 80 nM) of interacting MAIT cells, and develop compounds with diazirine-alkyne, biotin, or fluorophore labels for studying cellular MR1. Computer modelling casts new light on the molecular mechanism of activation, revealing that activators are first captured in MR1 via  pi-interactions and H-bonds, before tighter covalent bonding to Lys43 in MR1. This chemical study advances our molecular understanding of how bacterial metabolites are captured by MR1, influence cell surface expression of MR1, interact and modify human T cells; offering new clues for developing novel vaccine adjuvants, immunotherapeutics, and cancer drugs.
    Language English
    Publishing date 2024-04-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202400632
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection.

    Samer, Carolyn / McWilliam, Hamish E G / McSharry, Brian P / Velusamy, Thilaga / Burchfield, James G / Stanton, Richard J / Tscharke, David C / Rossjohn, Jamie / Villadangos, Jose A / Abendroth, Allison / Slobedman, Barry

    iScience

    2024  Volume 27, Issue 2, Page(s) 108801

    Abstract: The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 (HSV-1) ... ...

    Abstract The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 (HSV-1) infection there is a profound and rapid loss of MR1, in part due to expression of unique short 3 protein. Here we show that virion host shutoff RNase protein downregulates MR1 protein, through loss of MR1 transcripts. Furthermore, a third viral protein, infected cell protein 22, also downregulates MR1, but not classical MHC-I molecules. This occurs early in the MR1 trafficking pathway through proteasomal degradation. Finally, HSV-2 infection results in the loss of MR1 transcripts, and intracellular and surface MR1 protein, comparable to that seen during HSV-1 infection. Thus HSV coordinates a multifaceted attack on the MR1 antigen presentation pathway, potentially protecting infected cells from MAIT cell T cell receptor-mediated detection at sites of primary infection and reactivation.
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.108801
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation.

    Ashley, Caroline L / McSharry, Brian P / McWilliam, Hamish E G / Stanton, Richard J / Fielding, Ceri A / Mathias, Rommel A / Fairlie, David P / McCluskey, James / Villadangos, Jose A / Rossjohn, Jamie / Abendroth, Allison / Slobedman, Barry

    Frontiers in immunology

    2023  Volume 14, Page(s) 1107497

    Abstract: Introduction: The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis to mucosal-associated invariant T-cells (MAIT cells).: ... ...

    Abstract Introduction: The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis to mucosal-associated invariant T-cells (MAIT cells).
    Methods: Through in vitro human cytomegalovirus (HCMV) infection in the presence of MR1 ligand we investigate the modulation of MR1 expression. Using coimmunoprecipitation, mass spectrometry, expression by recombinant adenovirus and HCMV deletion mutants we investigate HCMV gpUS9 and its family members as potential regulators of MR1 expression. The functional consequences of MR1 modulation by HCMV infection are explored in coculture activation assays with either Jurkat cells engineered to express the MAIT cell TCR or primary MAIT cells. MR1 dependence in these activation assays is established by addition of MR1 neutralizing antibody and CRISPR/Cas-9 mediated MR1 knockout.
    Results: Here we demonstrate that HCMV infection efficiently suppresses MR1 surface expression and reduces total MR1 protein levels. Expression of the viral glycoprotein gpUS9 in isolation could reduce both cell surface and total MR1 levels, with analysis of a specific US9 HCMV deletion mutant suggesting that the virus can target MR1 using multiple mechanisms. Functional assays with primary MAIT cells demonstrated the ability of HCMV infection to inhibit bacterially driven, MR1-dependent activation using both neutralizing antibodies and engineered MR1 knockout cells.
    Discussion: This study identifies a strategy encoded by HCMV to disrupt the MR1:MAIT cell axis. This immune axis is less well characterized in the context of viral infection. HCMV encodes hundreds of proteins, some of which regulate the expression of antigen presentation molecules. However the ability of this virus to regulate the MR1:MAIT TCR axis has not been studied in detail.
    MeSH term(s) Humans ; Mucosal-Associated Invariant T Cells ; Histocompatibility Antigens Class I ; Cytomegalovirus/metabolism ; Minor Histocompatibility Antigens ; Receptors, Antigen, T-Cell/metabolism
    Chemical Substances Histocompatibility Antigens Class I ; Minor Histocompatibility Antigens ; Receptors, Antigen, T-Cell ; MR1 protein, human
    Language English
    Publishing date 2023-02-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1107497
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection

    Carolyn Samer / Hamish E.G. McWilliam / Brian P. McSharry / Thilaga Velusamy / James G. Burchfield / Richard J. Stanton / David C. Tscharke / Jamie Rossjohn / Jose A. Villadangos / Allison Abendroth / Barry Slobedman

    iScience, Vol 27, Iss 2, Pp 108801- (2024)

    2024  

    Abstract: Summary: The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 ( ... ...

    Abstract Summary: The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 (HSV-1) infection there is a profound and rapid loss of MR1, in part due to expression of unique short 3 protein. Here we show that virion host shutoff RNase protein downregulates MR1 protein, through loss of MR1 transcripts. Furthermore, a third viral protein, infected cell protein 22, also downregulates MR1, but not classical MHC-I molecules. This occurs early in the MR1 trafficking pathway through proteasomal degradation. Finally, HSV-2 infection results in the loss of MR1 transcripts, and intracellular and surface MR1 protein, comparable to that seen during HSV-1 infection. Thus HSV coordinates a multifaceted attack on the MR1 antigen presentation pathway, potentially protecting infected cells from MAIT cell T cell receptor-mediated detection at sites of primary infection and reactivation.
    Keywords Cell biology ; Immunology ; Virology ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Systemic inflammatory response syndrome triggered by blood-borne pathogens induces prolonged dendritic cell paralysis and immunosuppression.

    Ashayeripanah, Mitra / Vega-Ramos, Javier / Fernandez-Ruiz, Daniel / Valikhani, Shirin / Lun, Aaron T L / White, Jason T / Young, Louise J / Yaftiyan, Atefeh / Zhan, Yifan / Wakim, Linda / Caminschi, Irina / Lahoud, Mireille H / Lew, Andrew M / Shortman, Ken / Smyth, Gordon K / Heath, William R / Mintern, Justine D / Roquilly, Antoine / Villadangos, Jose A

    Cell reports

    2024  Volume 43, Issue 2, Page(s) 113754

    Abstract: Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by ... ...

    Abstract Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3-4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.
    MeSH term(s) Humans ; Blood-Borne Pathogens ; Immunosuppression Therapy ; Dendritic Cells ; Paralysis ; Systemic Inflammatory Response Syndrome
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.113754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Differential antigen requirements by diverse MR1-restricted T cells.

    Seneviratna, Rebecca / Redmond, Samuel J / McWilliam, Hamish Eg / Reantragoon, Rangsima / Villadangos, Jose A / McCluskey, James / I Godfrey, Dale / Gherardin, Nicholas A

    Immunology and cell biology

    2022  Volume 100, Issue 3, Page(s) 218

    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Unlocking autofluorescence in the era of full spectrum analysis: Implications for immunophenotype discovery projects.

    Jameson, Vanta J / Luke, Tina / Yan, Yuting / Hind, Angela / Evrard, Maximilien / Man, Kevin / Mackay, Laura K / Kallies, Axel / Villadangos, Jose A / McWilliam, Hamish E G / Perez-Gonzalez, Alexis

    Cytometry. Part A : the journal of the International Society for Analytical Cytology

    2022  Volume 101, Issue 11, Page(s) 922–941

    Abstract: Understanding the complex elements affecting signal resolution in cytometry is key for quality experimental design and data. In this study, we incorporate autofluorescence as a contributing factor to our understanding of resolution in cytometry and ... ...

    Abstract Understanding the complex elements affecting signal resolution in cytometry is key for quality experimental design and data. In this study, we incorporate autofluorescence as a contributing factor to our understanding of resolution in cytometry and corroborate its impact in fluorescence signal detection through mathematical predictions supported by empirical evidence. Our findings illustrate the critical importance of autofluorescence extraction via full spectrum unmixing in unmasking dim signals and delineating the expression and subset distribution of low abundance markers in discovery projects. We apply our findings to the precise definition of the tissue and cellular distribution of a weakly expressed fluorescent protein that reports on a low-abundance immunological gene. Exploiting the full spectrum coverage enabled by Aurora 5L, we describe a novel approach to the isolation of pure cell subset-specific autofluorescence profiles based on high dimensionality reduction algorithms. This method can also be used to unveil differences in the autofluorescent fingerprints of tissues in homeostasis and after immunological challenges.
    MeSH term(s) Immunophenotyping ; Coloring Agents ; Algorithms
    Chemical Substances Coloring Agents
    Language English
    Publishing date 2022-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099868-5
    ISSN 1552-4930 ; 0196-4763 ; 1552-4922
    ISSN (online) 1552-4930
    ISSN 0196-4763 ; 1552-4922
    DOI 10.1002/cyto.a.24555
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Dynamic Adjustment of Weighted GCC-PHAT for Position Estimation in an Ultrasonic Local Positioning System.

    Villadangos, José Manuel / Ureña, Jesús / García-Domínguez, Juan Jesús / Jiménez-Martín, Ana / Hernández, Álvaro / Pérez-Rubio, Mª Carmen

    Sensors (Basel, Switzerland)

    2021  Volume 21, Issue 21

    Abstract: Ultrasonic local positioning systems (ULPS) have been brought to the attention of researchers as one of the possibilities that can be used for indoor localization. Acoustic systems combine a suitable trade-off between precision, ease of development, and ... ...

    Abstract Ultrasonic local positioning systems (ULPS) have been brought to the attention of researchers as one of the possibilities that can be used for indoor localization. Acoustic systems combine a suitable trade-off between precision, ease of development, and cost. This work proposes a method for measuring the time of arrival of encoded emissions from a set of ultrasonic beacons, which are used to implement an accurate ULPS. This method uses the generalized cross-correlation technique with PHAT filter and weighting factor
    Language English
    Publishing date 2021-10-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2052857-7
    ISSN 1424-8220 ; 1424-8220
    ISSN (online) 1424-8220
    ISSN 1424-8220
    DOI 10.3390/s21217051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: LOCATE-US: Indoor Positioning for Mobile Devices Using Encoded Ultrasonic Signals, Inertial Sensors and Graph-Matching.

    Gualda, David / Pérez-Rubio, María Carmen / Ureña, Jesús / Pérez-Bachiller, Sergio / Villadangos, José Manuel / Hernández, Álvaro / García, Juan Jesús / Jiménez, Ana

    Sensors (Basel, Switzerland)

    2021  Volume 21, Issue 6

    Abstract: Indoor positioning remains a challenge and, despite much research and development carried out in the last decade, there is still no standard as with the Global Navigation Satellite Systems (GNSS) outdoors. This paper presents an indoor positioning system ...

    Abstract Indoor positioning remains a challenge and, despite much research and development carried out in the last decade, there is still no standard as with the Global Navigation Satellite Systems (GNSS) outdoors. This paper presents an indoor positioning system called LOCATE-US with adjustable granularity for use with commercial mobile devices, such as smartphones or tablets. LOCATE-US is privacy-oriented and allows every device to compute its own position by fusing ultrasonic, inertial sensor measurements and map information. Ultrasonic Local Positioning Systems (U-LPS) based on encoded signals are placed in critical zones that require an accuracy below a few decimeters to correct the accumulated drift errors of the inertial measurements. These systems are well suited to work at room level as walls confine acoustic waves inside. To avoid audible artifacts, the U-LPS emission is set at 41.67 kHz, and an ultrasonic acquisition module with reduced dimensions is attached to the mobile device through the USB port to capture signals. Processing in the mobile device involves an improved Time Differences of Arrival (TDOA) estimation that is fused with the measurements from an external inertial sensor to obtain real-time location and trajectory display at a 10 Hz rate. Graph-matching has also been included, considering available prior knowledge about the navigation scenario. This kind of device is an adequate platform for Location-Based Services (LBS), enabling applications such as augmented reality, guiding applications, or people monitoring and assistance. The system architecture can easily incorporate new sensors in the future, such as UWB, RFiD or others.
    Language English
    Publishing date 2021-03-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2052857-7
    ISSN 1424-8220 ; 1424-8220
    ISSN (online) 1424-8220
    ISSN 1424-8220
    DOI 10.3390/s21061950
    Database MEDical Literature Analysis and Retrieval System OnLINE

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