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  1. Article ; Online: Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection.

    Aguirre-Botero, Manuela C / Wang, Lawrence T / Formaglio, Pauline / Aliprandini, Eduardo / Thiberge, Jean-Michel / Schön, Arne / Flores-Garcia, Yevel / Mathis-Torres, Shamika / Flynn, Barbara J / da Silva Pereira, Lais / Le Duff, Yann / Hurley, Mathew / Nacer, Adéla / Bowyer, Paul W / Zavala, Fidel / Idris, Azza H / Francica, Joseph R / Seder, Robert A / Amino, Rogerio

    Cell reports

    2023  Volume 42, Issue 7, Page(s) 112681

    Abstract: Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using ... ...

    Abstract Human monoclonal antibodies (hmAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on the sporozoite surface are a promising tool for preventing malaria infection. However, their mechanisms of protection remain unclear. Here, using 13 distinctive PfCSP hmAbs, we provide a comprehensive view of how PfCSP hmAbs neutralize sporozoites in host tissues. Sporozoites are most vulnerable to hmAb-mediated neutralization in the skin. However, rare but potent hmAbs additionally neutralize sporozoites in the blood and liver. Efficient protection in tissues mainly associates with high-affinity and high-cytotoxicity hmAbs inducing rapid parasite loss-of-fitness in the absence of complement and host cells in vitro. A 3D-substrate assay greatly enhances hmAb cytotoxicity and mimics the skin-dependent protection, indicating that the physical stress imposed on motile sporozoites by the skin is crucial for unfolding the protective potential of hmAbs. This functional 3D cytotoxicity assay can thus be useful for downselecting potent anti-PfCSP hmAbs and vaccines.
    MeSH term(s) Animals ; Humans ; Plasmodium falciparum ; Malaria Vaccines ; Malaria ; Protozoan Proteins ; Immunoglobulins ; Sporozoites ; Malaria, Falciparum
    Chemical Substances Malaria Vaccines ; Protozoan Proteins ; Immunoglobulins
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Innate immunity including epithelial and nonspecific host factors: workshop 1B.

    Weinberg, A / Naglik, J R / Kohli, A / Tugizov, S M / Fidel, P L / Liu, Y / Herzberg, M

    Advances in dental research

    2011  Volume 23, Issue 1, Page(s) 122–129

    Abstract: The majority of HIV infections are initiated at mucosal sites. The oral mucosal tissue has been shown to be a potential route of entry in humans and primates. Whereas HIV RNA, proviral DNA, and infected cells are detected in the oral mucosa and saliva of ...

    Abstract The majority of HIV infections are initiated at mucosal sites. The oral mucosal tissue has been shown to be a potential route of entry in humans and primates. Whereas HIV RNA, proviral DNA, and infected cells are detected in the oral mucosa and saliva of infected individuals, it appears that the oral mucosa is not permissive for efficient HIV replication and therefore may differ in susceptibility to infection when compared to other mucosal sites. Since there is no definitive information regarding the fate of the HIV virion in mucosal epithelium, there is a pressing need to understand what occurs when the virus is in contact with this tissue, what mechanisms are in play to determine the outcome, and to what degree the mechanisms and outcomes differ between mucosal sites. Workshop 1B tackled 5 important questions to define current knowledge about epithelial cell-derived innate immune agents, commensal and endogenous pathogens, and epithelial cells and cells of the adaptive immune system and how they contribute to dissemination or resistance to HIV infection. Discovering factors that explain the differential susceptibility and resistance to HIV infection in mucosal sites will allow for the identification and development of novel protective strategies.
    MeSH term(s) Animals ; Cytokines/physiology ; Defensins/physiology ; Dendritic Cells/physiology ; Epithelial Cells/physiology ; Epithelial Cells/virology ; Female ; Focus Groups ; HIV Infections/immunology ; HIV-1/physiology ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Leukocytes/physiology ; Maternal-Fetal Exchange ; Mouth Mucosa/immunology ; Mouth Mucosa/virology ; Pregnancy ; Saliva/immunology ; Saliva/virology ; Secretory Leukocyte Peptidase Inhibitor/physiology ; Superinfection/microbiology ; Superinfection/virology ; Virus Internalization
    Chemical Substances Cytokines ; Defensins ; Secretory Leukocyte Peptidase Inhibitor
    Language English
    Publishing date 2011-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639406-1
    ISSN 1544-0737 ; 0895-9374
    ISSN (online) 1544-0737
    ISSN 0895-9374
    DOI 10.1177/0022034511399917
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A single-cell RNA-sequencing training and analysis suite using the Galaxy framework.

    Tekman, Mehmet / Batut, Bérénice / Ostrovsky, Alexander / Antoniewski, Christophe / Clements, Dave / Ramirez, Fidel / Etherington, Graham J / Hotz, Hans-Rudolf / Scholtalbers, Jelle / Manning, Jonathan R / Bellenger, Lea / Doyle, Maria A / Heydarian, Mohammad / Huang, Ni / Soranzo, Nicola / Moreno, Pablo / Mautner, Stefan / Papatheodorou, Irene / Nekrutenko, Anton /
    Taylor, James / Blankenberg, Daniel / Backofen, Rolf / Grüning, Björn

    GigaScience

    2020  Volume 9, Issue 10

    Abstract: Background: The vast ecosystem of single-cell RNA-sequencing tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x ... ...

    Abstract Background: The vast ecosystem of single-cell RNA-sequencing tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically driven methods needed to process and understand these ever-growing datasets.
    Results: Here we outline several Galaxy workflows and learning resources for single-cell RNA-sequencing, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows, and trainings that not only enable users to perform 1-click 10x preprocessing but also empower them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal, and clustering. The teaching resources cover concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal.
    Conclusions: The reproducible and training-oriented Galaxy framework provides a sustainable high-performance computing environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy community provide a means for users to learn, publish, and teach single-cell RNA-sequencing analysis.
    MeSH term(s) Computational Biology ; Ecosystem ; RNA ; Sequence Analysis, RNA ; Software
    Chemical Substances RNA (63231-63-0)
    Keywords covid19
    Language English
    Publishing date 2020-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2708999-X
    ISSN 2047-217X ; 2047-217X
    ISSN (online) 2047-217X
    ISSN 2047-217X
    DOI 10.1093/gigascience/giaa102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: In vivo virulence of Candida albicans isolates causing mucosal infections in people infected with the human immunodeficiency virus.

    Taylor, B N / Fichtenbaum, C / Saavedra, M / Slavinsky III, J / Swoboda, R / Wozniak, K / Arribas, A / Powderly, W / Fidel Jr, P L

    The Journal of infectious diseases

    2000  Volume 182, Issue 3, Page(s) 955–959

    Abstract: Mucosal candidiasis is common in human immunodeficiency virus (HIV) infection. Susceptibility to such infections may be attributed to reduced host defense mechanisms and/or virulence of the organism. In the present study, we compared the virulence of ... ...

    Abstract Mucosal candidiasis is common in human immunodeficiency virus (HIV) infection. Susceptibility to such infections may be attributed to reduced host defense mechanisms and/or virulence of the organism. In the present study, we compared the virulence of mucosal Candida albicans isolates from HIV-infected people, with and without fluconazole-refractory infection, in established murine models of systemic and vaginal candidiasis. Compared with the mortality rate ( approximately 70%) after intravenous challenge with 2 virulent reference isolates, challenge with most clinical isolates (66%-77%) resulted in prolonged survival. In contrast, fungal burden induced by intravaginal challenge of nearly all (97%) isolates was similar to that of the virulent controls. There were no differences in in vitro growth rates for any of the isolates, and there was no association between reduced mortality and clinical failure to fluconazole, in vitro antifungal susceptibility, site of infection, or other host factors. These results suggest that virulence of C. albicans is tissue specific and is not a factor in the development of fluconazole-refractory infections in advanced HIV disease.
    MeSH term(s) AIDS-Related Opportunistic Infections/microbiology ; Animals ; Antifungal Agents/therapeutic use ; Candida albicans/isolation & purification ; Candida albicans/pathogenicity ; Candidiasis/microbiology ; Drug Resistance, Microbial ; Female ; Fluconazole/therapeutic use ; Humans ; Mice ; Mice, Inbred CBA
    Chemical Substances Antifungal Agents ; Fluconazole (8VZV102JFY)
    Language English
    Publishing date 2000-09
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1086/315768
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

    Raman, Betty / Cassar, Mark Philip / Tunnicliffe, Elizabeth M / Filippini, Nicola / Griffanti, Ludovica / Alfaro-Almagro, Fidel / Okell, Thomas / Sheerin, Fintan / Xie, Cheng / Mahmod, Masliza / Mózes, Ferenc E / Lewandowski, Adam J / Ohuma, Eric O / Holdsworth, David / Lamlum, Hanan / Woodman, Myles J / Krasopoulos, Catherine / Mills, Rebecca / McConnell, Flora A Kennedy /
    Wang, Chaoyue / Arthofer, Christoph / Lange, Frederik J / Andersson, Jesper / Jenkinson, Mark / Antoniades, Charalambos / Channon, Keith M / Shanmuganathan, Mayooran / Ferreira, Vanessa M / Piechnik, Stefan K / Klenerman, Paul / Brightling, Christopher / Talbot, Nick P / Petousi, Nayia / Rahman, Najib M / Ho, Ling-Pei / Saunders, Kate / Geddes, John R / Harrison, Paul J / Pattinson, Kyle / Rowland, Matthew J / Angus, Brian J / Gleeson, Fergus / Pavlides, Michael / Koychev, Ivan / Miller, Karla L / Mackay, Clare / Jezzard, Peter / Smith, Stephen M / Neubauer, Stefan

    EClinicalMedicine

    2021  Volume 31, Page(s) 100683

    Abstract: Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.: Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, ... ...

    Abstract Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.
    Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments.
    Findings: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (
    Interpretation: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness.
    Funding: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.
    Language English
    Publishing date 2021-01-07
    Publishing country England
    Document type Journal Article
    ISSN 2589-5370
    ISSN (online) 2589-5370
    DOI 10.1016/j.eclinm.2020.100683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework

    Tekman, Mehmet / Batut, Bérénice / Ostrovsky, Alexander / Antoniewski, Christophe / Clements, Dave / Ramirez, Fidel / Etherington, Graham J / Hotz, Hans-Rudolf / Scholtalbers, Jelle / Manning, Jonathan R / Bellenger, Lea / Doyle, Maria A / Heydarian, Mohammad / Huang, Ni / Soranzo, Nicola / Moreno, Pablo / Papatheodorou, Irene / Nekrutenko, Anton / Taylor, James /
    Blankenberg, Daniel / Backofen, Rolf / Grüning, Björn

    bioRxiv

    Abstract: Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics ... ...

    Abstract Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically-driven methods needed to process and understand these ever-growing datasets. Results Here we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows and trainings that not only enable users to perform one-click 10x preprocessing, but also empowers them to demultiplex raw sequencing data manually. The downstream analysis supports a wide range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal and clustering. The teaching resources cover an assortment of different concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal. Conclusions The reproducible and training-oriented Galaxy framework provides a sustainable HPC environment for users to run flexible analyses on both 10x and alternatively derived datasets. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy Community provide a means for users to learn, publish and teach scRNA-seq analysis. Key Points Single-cell RNA-seq has stabilised towards 10x Genomics datasets. Galaxy provides rich and reproducible scRNA-seq workflows with a wide range of robust tools. The Galaxy Training Network provides tutorials for the processing of both 10x and non-10x datasets.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.06.06.137570
    Database COVID19

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  7. Article ; Online: A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework

    Tekman, Mehmet / Batut, Bérénice / Ostrovsky, Alexander / Antoniewski, Christophe / Clements, Dave / Ramirez, Fidel / Etherington, Graham J / Hotz, Hans-Rudolf / Scholtalbers, Jelle / Manning, Jonathan R / Bellenger, Lea / Doyle, Maria A / Heydarian, Mohammad / Huang, Ni / Soranzo, Nicola / Moreno, Pablo / Mautner, Stefan / Papatheodorou, Irene / Nekrutenko, Anton /
    Taylor, James / Blankenberg, Daniel / Backofen, Rolf / Grüning, Björn

    bioRxiv

    Abstract: Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics ... ...

    Abstract Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically-driven methods needed to process and understand these ever-growing datasets. Results Here we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows and trainings that not only enable users to perform one-click 10x preprocessing, but also empowers them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a wide range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal and clustering. The teaching resources cover an assortment of different concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal. Conclusions The reproducible and training-oriented Galaxy framework provides a sustainable HPC environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy Community provide a means for users to learn, publish and teach scRNA-seq analysis. Key Points Single-cell RNA-seq has stabilised towards 10x Genomics datasets. Galaxy provides rich and reproducible scRNA-seq workflows with a wide range of robust tools. The Galaxy Training Network provides tutorials for the processing of both 10x and non-10x datasets.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.06.06.137570
    Database COVID19

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  8. Article: Fungal infections associated with HIV infection.

    Samaranayake, L P / Fidel, P L / Naglik, J R / Sweet, S P / Teanpaisan, R / Coogan, M M / Blignaut, E / Wanzala, P

    Oral diseases

    2002  Volume 8 Suppl 2, Page(s) 151–160

    Abstract: Oral candidiasis is perhaps the commonest infection seen in HIV disease. The aim of this workshop was to provide a sketch of the multifarious aspects of the disease from a global perspective. To this end the panellists addressed issues such as the ... ...

    Abstract Oral candidiasis is perhaps the commonest infection seen in HIV disease. The aim of this workshop was to provide a sketch of the multifarious aspects of the disease from a global perspective. To this end the panellists addressed issues such as the virulence of Candida, emergence of antifungal resistance, management of candidiasis and other exotic, oral mycotic diseases. An all-pervasive theme was the dramatic differences in the management of fungal infections consequential to the availability (or the lack) of anti-HIV drugs in the developed and the developing world. Further, the social stigmata associated with the HIV disease in many developing regions in Africa and Asia appears to modify the therapeutic strategies. Additionally, the lesser-known regional variations in the disease manifestations and therapeutic approaches were stark. Further work is direly needed to address these issues.
    MeSH term(s) AIDS-Related Opportunistic Infections/complications ; Africa ; Anti-HIV Agents/therapeutic use ; Antifungal Agents/therapeutic use ; Asia ; Azoles/therapeutic use ; Candida/classification ; Candida/genetics ; Candida/pathogenicity ; Candidiasis, Oral/complications ; Candidiasis, Oral/prevention & control ; Developed Countries ; Developing Countries ; Drug Resistance, Fungal ; Erythema/microbiology ; Genotype ; Global Health ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Mouth Diseases/microbiology ; Mycoses/complications ; Phenotype ; Social Environment ; Virulence
    Chemical Substances Anti-HIV Agents ; Antifungal Agents ; Azoles
    Language English
    Publishing date 2002-08-06
    Publishing country Denmark
    Document type Journal Article ; Review
    ZDB-ID 1290529-x
    ISSN 1601-0825 ; 1354-523X
    ISSN (online) 1601-0825
    ISSN 1354-523X
    DOI 10.1034/j.1601-0825.8.s2.6.x
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  9. Article: Resistance of T-cell receptor delta-chain-deficient mice to experimental Candida albicans vaginitis.

    Wormley, F L / Steele, C / Wozniak, K / Fujihashi, K / McGhee, J R / Fidel, P L

    Infection and immunity

    2001  Volume 69, Issue 11, Page(s) 7162–7164

    Abstract: Conditions consistent with tolerance or immunoregulation have been observed in experimental Candida albicans vaginal infections. The present study investigated the role of gamma/delta T cells in experimental vaginal candidiasis. Results showed that T- ... ...

    Abstract Conditions consistent with tolerance or immunoregulation have been observed in experimental Candida albicans vaginal infections. The present study investigated the role of gamma/delta T cells in experimental vaginal candidiasis. Results showed that T-cell receptor delta-chain-knockout mice had significantly less vaginal fungal burden when compared to wild-type mice, suggesting an immunoregulatory role for gamma/delta T cells in Candida vaginitis.
    MeSH term(s) Animals ; Candidiasis/immunology ; Disease Models, Animal ; Female ; Hypersensitivity, Delayed/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nitrogen Oxides/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; T-Lymphocytes/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; Vaginitis/immunology
    Chemical Substances Nitrogen Oxides ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2001-11
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.69.11.7162-7164.2001
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