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Immunoprophylaxis and Therapy Commons

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Adenovirus Prime, Env Protein Boost Vaccine Protects Against Neutralization-Resistant Sivsme660 Variants In Rhesus Monkeys, Brandon F. Keele, Wenjun Li, Erica N. Borducchi, Joseph P. Nkolola, Peter Abbink, Bing Chen, Michael S. Seaman, Dan H. Barouch 2017 Frederick National Laboratory for Cancer Research

Adenovirus Prime, Env Protein Boost Vaccine Protects Against Neutralization-Resistant Sivsme660 Variants In Rhesus Monkeys, Brandon F. Keele, Wenjun Li, Erica N. Borducchi, Joseph P. Nkolola, Peter Abbink, Bing Chen, Michael S. Seaman, Dan H. Barouch

Wenjun Li

Previous studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01B-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines. In a single, high-dose challenge study, only the Ad/Env vaccine affords significant protection against acquisition ...


5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. McElvaney, Terence R. Flotte 2017 University of Massachusetts Medical School

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...


The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello 2017 University of Massachusetts Medical School

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

Neal Silverman

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...


5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. McElvaney, Terence R. Flotte 2017 University of Massachusetts Medical School

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

University of Massachusetts Medical School Faculty Publications

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...


Balb/C Mice Immunized With A Combination Of Virus-Like Particles Incorporating Kaposi Sarcoma-Associated Herpesvirus (Kshv) Envelope Glycoproteins Gpk8.1, Gb, And Gh/Gl Induced Comparable Serum Neutralizing Antibody Activity To Uv-Inactivated Kshv, Anne K. Barasa, Peng Ye, Meredith Phelps, Ganapathiram T. Arivudainambi, Timelia Tison, Javier Gordon Ogembo 2017 Beckman Research Institute of City of Hope, CA

Balb/C Mice Immunized With A Combination Of Virus-Like Particles Incorporating Kaposi Sarcoma-Associated Herpesvirus (Kshv) Envelope Glycoproteins Gpk8.1, Gb, And Gh/Gl Induced Comparable Serum Neutralizing Antibody Activity To Uv-Inactivated Kshv, Anne K. Barasa, Peng Ye, Meredith Phelps, Ganapathiram T. Arivudainambi, Timelia Tison, Javier Gordon Ogembo

Open Access Articles

Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring in Africa, where the virus is endemic. To date, there is no prophylactic vaccine against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus entry into host cells, are attractive vaccine targets for eliciting potent neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1, gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized these VLPs for their composition, size, and functionality. To determine which viral glycoprotein(s) elicit ...


Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli, Serena Giuntini, Matteo Stoppato, Monir Ejemel, Danielle Wisheart, Mark S. Klempner, Yan Wang 2017 University of Massachusetts Medical School

Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli, Serena Giuntini, Matteo Stoppato, Monir Ejemel, Danielle Wisheart, Mark S. Klempner, Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

Background. Enterotoxigenic Escherichia coli (ETEC) infections are the major cause of diarrheal morbidity among children living in developing countries. ETEC mediates small intestine adherence through bacterial adhesion followed by production of enterotoxins that induce diarrhea. Currently there is no vaccine available for ETEC. One of the most predominant adhesin of pathogenic ETEC strains is colonization factor antigen I (CFA/I). The CFA/I adhesion tip, CfaE, is required for ETEC binding to human intestinal cells and colonization. Human antibodies against CfaE have potential to block colonization of ETEC and serve as a potent immunoprophylactic against ETEC-related diarrhea.

Methods. A panel ...


Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya 2017 University of Southern Mississippi

Elucidating The Role Of Interleukin-17a In West Nile Virus Infection, Dhiraj Acharya

Dissertations

West Nile virus (WNV) is a neurotropic flavivirus of significant public health importance for which no therapeutics and vaccine are currently available. Interleukin-17A (IL-17A) is an inflammatory cytokine that regulates diverse immune functions, while its role is unclear in host’s immune response to WNV. Furthermore, CD8+ T cells are crucial components of immunity and play a vital role in recovery from WNV infection. Here, we report a previously unrecognized function of IL-17A in regulating CD8+ T cell cytotoxicity. We show that WNV induces the expression of IL-17A in both mouse splenocytes and human peripheral blood mononuclear cells cultured in ...


Sickle Cell Anemia: Current Treatments And Potential Advancements, Vanessa Martinez 2017 Southeastern University - Lakeland

Sickle Cell Anemia: Current Treatments And Potential Advancements, Vanessa Martinez

Selected Honors Theses

Sickle cell anemia is a disease that affects red blood cells, specifically the hemoglobin protein. An amino acid mutation in the gene that encodes β-globin leads to malformation of the β subunit of hemoglobin.3, Valine becomes glutamic acid in the mutated β-globin gene.9 The mutation malformation leads to the red blood cells becoming sickle shaped, or crescent shaped.3,4 The sickle shape of red blood cells in individuals with sickle cell disease leads to vaso-occlusive crisis.9 Vaso-occlusive crisis includes complications such as blood clotting, chronic pain, organ failure, organ death, and possibly early mortality.9 The ...


Allele-Selective Suppression Of Mutant Huntingtin In Primary Human Blood Cells, James R. C. Miller, Edith L. Pfister, Wanzhao Liu, Ralph Andre, Ulrike Trager, Lori A. Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary R. Ostroff, Neil Aronin, Sarah J. Tabrizi 2017 University College London

Allele-Selective Suppression Of Mutant Huntingtin In Primary Human Blood Cells, James R. C. Miller, Edith L. Pfister, Wanzhao Liu, Ralph Andre, Ulrike Trager, Lori A. Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary R. Ostroff, Neil Aronin, Sarah J. Tabrizi

Open Access Articles

Post-transcriptional gene silencing is a promising therapy for the monogenic, autosomal dominant, Huntington's disease (HD). However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis. Highly selective mRNA knockdown was achieved when targeting each allele of rs362331 in exon 50 of the HTT transcript; this selectivity was ...


Binding Of A Monoclonal Antibody To B Virus Gd Linear Epitope On A Whole Virus Antigen Is Only After Antigen Denaturation, Jingyao Deng 2017 Georgia State University

Binding Of A Monoclonal Antibody To B Virus Gd Linear Epitope On A Whole Virus Antigen Is Only After Antigen Denaturation, Jingyao Deng

Georgia State Undergraduate Research Conference

No abstract provided.


Novel Epstein-Barr Virus-Like Particles Incorporating Gh/Gl-Ebna1 Or Gb-Lmp2 Induce High Neutralizing Antibody Titers And Ebv-Specific T-Cell Responses In Immunized Mice, Elizabeth M. Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo 2017 University of Massachusetts Medical School

Novel Epstein-Barr Virus-Like Particles Incorporating Gh/Gl-Ebna1 Or Gb-Lmp2 Induce High Neutralizing Antibody Titers And Ebv-Specific T-Cell Responses In Immunized Mice, Elizabeth M. Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo

Open Access Articles

Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines. To boost the humoral response and trigger cell-mediated immunity, EBV nuclear antigen 1 (EBNA1) and latent membrane ...


The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello 2017 University of Massachusetts Medical School

The Antiviral Rna Interference Response Provides Resistance To Lethal Arbovirus Infection And Vertical Transmission In Caenorhabditis Elegans, Don B. Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal S. Silverman, Craig C. Mello

University of Massachusetts Medical School Faculty Publications

The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C. elegans. Furthermore, we find nematodes deficient for components of the antiviral RNAi ...


Impact Of A National Guideline On Antibiotic Selection For Hospitalized Pneumonia., Derek J Williams, Matthew Hall, Jeffrey S Gerber, Mark I Neuman, Adam L Hersh, Thomas V Brogan, Kavita Parikh, Sanjay Mahant, Anne J Blaschke, Samir S Shah, Carlos G Grijalva 2017 George Washington University

Impact Of A National Guideline On Antibiotic Selection For Hospitalized Pneumonia., Derek J Williams, Matthew Hall, Jeffrey S Gerber, Mark I Neuman, Adam L Hersh, Thomas V Brogan, Kavita Parikh, Sanjay Mahant, Anne J Blaschke, Samir S Shah, Carlos G Grijalva

Pediatrics Faculty Publications

BACKGROUND: We evaluated the impact of the 2011 Pediatric Infectious Diseases Society/Infectious Diseases Society of America pneumonia guideline and hospital-level implementation efforts on antibiotic prescribing for children hospitalized with pneumonia.

METHODS: We assessed inpatient antibiotic prescribing for pneumonia at 28 children's hospitals between August 2009 and March 2015. Each hospital was also surveyed regarding local implementation efforts targeting antibiotic prescribing and organizational readiness to adopt guideline recommendations. To estimate guideline impact, we used segmented linear regression to compare the proportion of children receiving penicillins in March 2015 with the expected proportion at this same time point had the ...


Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Aaron J. Belli, Keith A. Reimann, Margaret E. Ackerman 2016 Dartmouth College

Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Aaron J. Belli, Keith A. Reimann, Margaret E. Ackerman

Open Access Articles

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcgammaR) and their ability ...


Immunotherapeutic Strategies To Reverse Tumor Associated Immunosuppression In Breast Cancer, Sruthi Ravindranathan 2016 University of Arkansas, Fayetteville

Immunotherapeutic Strategies To Reverse Tumor Associated Immunosuppression In Breast Cancer, Sruthi Ravindranathan

Theses and Dissertations

Heterogenous cancers such as breast carcinoma, would highly benefit from personalized vaccine approaches such as autologous tumor cell vaccines (ATCVs). By using cancer cells that are isolated from self, this approach has the potential to generate a polyclonal immune response against tumor antigens, that are specific to the individual. However, so far, ATCVs against breast cancers have not had any clinical success due to the poor immunogenicity of the malignant cells.

In this study, for the first time, we determined tumor derived G-CSF to play a major role in affecting immune response against breast cancer ATCVs. By using CRISPR/Cas9 ...


The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista 2016 University of Massachusetts Medical School

The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista

GSBS Dissertations and Theses

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late ...


Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa 2016 University of Massachusetts Medical School

Fc Receptor-Mediated Activities Of Env-Specific Monoclonal Antibodies Generated From Human Volunteers Receiving A Dna Prime-Protein Boost Hiv Vaccine: A Dissertation, Matthew R. Costa

GSBS Dissertations and Theses

Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc ...


A Chimeric Protein-Based Malaria Vaccine Candidate Induces Robust T Cell Responses Against Plasmodium Vivax Msp119, Jairo Andres Fonseca, Monica Cabrera-Mora, Balwan Singh, Joseli Oliveira-Ferreira, Josue Da Costa Lima-Junior, J. Mauricio Calvo-Calle, Jose Manuel Lozano, Alberto Moreno 2016 Emory University

A Chimeric Protein-Based Malaria Vaccine Candidate Induces Robust T Cell Responses Against Plasmodium Vivax Msp119, Jairo Andres Fonseca, Monica Cabrera-Mora, Balwan Singh, Joseli Oliveira-Ferreira, Josue Da Costa Lima-Junior, J. Mauricio Calvo-Calle, Jose Manuel Lozano, Alberto Moreno

Open Access Articles

The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119. This vaccine candidate ...


Tuberculosis Susceptibility And Vaccine Protection Are Independently Controlled By Host Genotype, Clare M. Smith, Megan K. Proulx, Andrew J. Olive, Dominick Laddy, Bibhuti B. Mishra, Caitlin Moss, Nuria Martinez, Michelle M. Bellerose, Palmira Barreira-Silva, Jia Yao Phuah, Richard E. Baker, Samuel M. Behar, Hardy Kornfeld, Thomas G. Evans, Gillian Beamer, Christopher M. Sassetti 2016 University of Massachusetts Medical School

Tuberculosis Susceptibility And Vaccine Protection Are Independently Controlled By Host Genotype, Clare M. Smith, Megan K. Proulx, Andrew J. Olive, Dominick Laddy, Bibhuti B. Mishra, Caitlin Moss, Nuria Martinez, Michelle M. Bellerose, Palmira Barreira-Silva, Jia Yao Phuah, Richard E. Baker, Samuel M. Behar, Hardy Kornfeld, Thomas G. Evans, Gillian Beamer, Christopher M. Sassetti

Open Access Articles

The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the "Collaborative Cross" project. Unlike natural populations ...


Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen 2016 University of Massachusetts Medical School

Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen

Open Access Articles

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were ...


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