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  • 1
    Online Resource
    Online Resource
    Irish society of gastroenterlogy : Proceedings of Winter Meeting, Belfast City Hospital, Friday 24th and Saturday 25th November, 1989
    Springer Science and Business Media LLC ; 1990
    In:  Irish Journal of Medical Science Vol. 159, No. 7 ( 1990-7), p. 219-225
    Details
    In: Irish Journal of Medical Science, Springer Science and Business Media LLC, Vol. 159, No. 7 ( 1990-7), p. 219-225
    Type of Medium: Online Resource
    ISSN: 0021-1265 , 1863-4362
    URL: Article
    DOI: 10.1007/BF02937271
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1990
    detail.hit.zdb_id: 2275855-0
    detail.hit.zdb_id: 2468506-9
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Go for gold: Integrating process and product in ESP
    Elsevier BV ; 1992
    In:  English for Specific Purposes Vol. 11, No. 3 ( 1992-1), p. 225-242
    Details
    In: English for Specific Purposes, Elsevier BV, Vol. 11, No. 3 ( 1992-1), p. 225-242
    Type of Medium: Online Resource
    ISSN: 0889-4906
    URL: Article
    DOI: 10.1016/S0889-4906(05)80011-0
    RVK:
    HC 1000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1992
    detail.hit.zdb_id: 1480709-9
    SSG: 7,25
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Feedback on second language students' writing
    Cambridge University Press (CUP) ; 2006
    In:  Language Teaching Vol. 39, No. 2 ( 2006-04), p. 83-101
    Details
    In: Language Teaching, Cambridge University Press (CUP), Vol. 39, No. 2 ( 2006-04), p. 83-101
    Abstract: Feedback is widely seen as crucial for encouraging and consolidating learning, and this significance has also been recognised by those working in the field of second language (L2) writing. Its importance is acknowledged in process-based classrooms, where it forms a key element of the students' growing control over composing skills, and by genre-oriented teachers employing scaffolded learning techniques. In fact, over the past twenty years, changes in writing pedagogy and research have transformed feedback practices, with teacher written comments often supplemented with peer feedback, writing workshops, conferences, and computer-delivered feedback. But while feedback is a central aspect of ESL/EFL writing programs across the world, the research literature has not been unequivocally positive about its role in writing development, and teachers often have a sense that they are not making use of its full potential. In this paper we examine recent research related to feedback on L2 students' writing, focusing on the role of feedback in writing instruction and discussing current issues relating to teacher written and oral feedback, collaborative peer feedback and computer-mediated feedback.
    Type of Medium: Online Resource
    ISSN: 0261-4448 , 1475-3049
    URL: Article
    DOI: 10.1017/S0261444806003399
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2006
    detail.hit.zdb_id: 2079708-4
    SSG: 7,20
    SSG: 7,11
    SSG: 5,3
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    Online Resource
  • 4
    Online Resource
    Online Resource
    Sugaring the pill
    Elsevier BV ; 2001
    In:  Journal of Second Language Writing Vol. 10, No. 3 ( 2001-8), p. 185-212
    Details
    In: Journal of Second Language Writing, Elsevier BV, Vol. 10, No. 3 ( 2001-8), p. 185-212
    Type of Medium: Online Resource
    ISSN: 1060-3743
    URL: Article
    DOI: 10.1016/S1060-3743(01)00038-8
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 2019441-9
    detail.hit.zdb_id: 1135834-8
    SSG: 7,11
    SSG: 7,24
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Demographic history and rare allele sharing among human populations
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Abstract: High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1019276108
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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    Online Resource
  • 6
    Online Resource
    Online Resource
    A global reference for human genetic variation
    Springer Science and Business Media LLC ; 2015
    In:  Nature Vol. 526, No. 7571 ( 2015-10-01), p. 68-74
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 526, No. 7571 ( 2015-10-01), p. 68-74
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/nature15393
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Estimating mutation load at 5% LOD from FFPE samples using a targeted next-generation sequencing assay.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 5_suppl ( 2018-02-10), p. 28-28
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 5_suppl ( 2018-02-10), p. 28-28
    Abstract: 28 Background: High tumor mutation load is a biomarker which positively correlates with response to immune checkpoint inhibitors. Current methods to estimate tumor mutation load often require large amounts of DNA. Herein, we demonstrate the ability of a targeted panel to estimate mutation load from FFPE samples using low input amount of DNA. Methods: We developed a single-sample analysis workflow to estimate mutation load (somatic mutation count per Megabase (Mb)) from FFPE and fresh frozen tumor research samples. The assay utilizes a PCR-based target enrichment panel that covers ~1.7 Mb. Our workflow requires only 10 ng of input DNA, and enables a 2.5-day turn-around time from sample to the final report. The workflow enables 〈 60 minutes of hands-on time for automated library preparation and templating on a batch of 8 samples. Sequencing is performed using a high throughput semiconductor sequencing platform to achieve sufficient depth (~500x coverage) and accuracy. Our analysis pipeline calls variants with optimized parameters on the tumor sample only, with no matched normal sample required, and applies filters to remove germ-line. Results: An in-silico analysis using 21,000 exomes from COSMIC demonstrated the panel can achieve high sensitivity ( 〉 =93%) and specificity ( 〉 99%) necessary to stratify high and low mutation burden samples. Matched tumor-normal analyses on 14 lung and colorectal samples showed that our single tumor analysis workflow detects mutation load with strong correlation (r=0.8699) with tumor-normal analysis. Through dilution experiments on engineered control we learned that the workflow provides accurate estimates of mutation load, predicting ± 7% of expected mutation load on 〉 =20% tumor content. To assess reproducibility, we compared mutation load in library replicates for a cohort of 8 samples (FFPE and fresh frozen tumors, engineered control, and NIST cell-lines) and observed high correlation (r=0.9906) among replicates. Conclusions: We developed a simple workflow on the Ion Torrent sequencing platform to estimate mutation load from FFPE and fresh frozen tumor research samples. This solution will advance research in immuno-oncology.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.5_suppl.28
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Somatic mutation burden in cancer samples determined by targeted next generation sequencing.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 7_suppl ( 2017-03-01), p. 15-15
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 7_suppl ( 2017-03-01), p. 15-15
    Abstract: 15 Background: High somatic mutation burden in tumor tissues is associated with the presentation of neoantigens that promote immune responses particularly in the context of immune checkpoint therapies. Herein, we characterize the ability of targeted cancer research panels to generate estimates of somatic mutation burden. Methods: Somatic mutation data from 〉 8000 cancer samples obtained from The Cancer Genome Atlas (TCGA) was curated and standardized, and the number of single nucleotide variants (SNVs) in exonic regions of each sample determined. Next, the number of SNVs associated with target regions of two Ion AmpliSeq cancer panels (Oncomine Comprehensive Assay [OCA, 146 genes, 0.35 MB]; Comprehensive Cancer Panel [CCP, 409 genes, 1.7 MB] ) was likewise determined and the frequency of mutation counts in the exome and the panel target regions was compared. Mutation counts of samples containing truncating mutations in mismatch repair (MMR) and other DNA repair genes were characterized. A facile workflow with less than 60 minutes of hands-on time was developed to estimate mutation counts for a batch of 8 samples using the Ion Chef for automated library preparation and templating followed by sequencing on the Ion S5. Results: The sensitivity of targeted panels in estimating somatic mutation burden was positively correlated with panel size. The area under the Receiver Operating Characteristic (ROC) curve showed that CCP had 〉 90% sensitivity and 〉 95% specificity to differentiate high and low mutation burden based on informatics analysis of TCGA data. As expected, truncating mutations in MMR genes were associated with higher somatic mutation counts in colorectal tumor tissue. Using data generated from OCA and CCP, we characterized a set of filters that provided a good estimate of somatic mutation counts when applied to a tumor-only workflow. Conclusions: A simple workflow was developed on the Ion Torrent sequencing platform to estimate somatic mutation burden in cancer samples. The methods described herein will help advance research in immuo-oncology.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.7_suppl.15
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Long-amplicon TCRβ repertoire sequencing to reveal human T-cell receptor variable gene polymorphism: Implications for the prediction and interpretation of immunotherapy outcome.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 5_suppl ( 2018-02-10), p. 129-129
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 5_suppl ( 2018-02-10), p. 129-129
    Abstract: 129 Background: Human T cell antigen receptors play a critical role in protective immune responses but are also implicated in autoimmune disease and immune-mediated adverse events during immunotherapy. The antigen specificity of the T cell receptor is determined in part by the sequence of the CDR and Framework regions encoded by the TCRB variable gene. Previous studies of population sequencing data indicate that current antigen receptor allele databases, such as IMGT, fail to capture a significant portion of human variation. Here we use long-amplicon multiplex sequencing of rearranged TCRB receptors to validate putative novel human variable gene alleles previously recovered from 1000 genomes data. Methods: TCRB rearrangements were amplified from cDNA from 85 Caucasians undergoing treatment for melanoma using AmpliSeq-based multiplex Framework 1 and Constant gene primers to produce ~330bp amplicons. Samples were sequenced using the Ion Torrent S5 530 chip to produce ~1.5M raw reads per sample. Ion Reporter was used for clonotyping and identification of variable gene sequences absent from the IMGT database. Putatively novel sequences were compared to those reported in the Lym1k database of alleles recovered from 1000 genomes data. Results: We identified 15 novel variable gene alleles that are absent from the IMGT database and result in amino acid changes to the CDR or Framework regions of the TCR. Typically, a single individual was found to be heterozygous for a novel variant, though we note two instances where multiple individuals possessed a novel variant. We also identified novel variable gene alleles that are absent from the Lym1k database, potentially due to challenges in inferring receptor alleles from short-read population sequencing studies. Conclusions: We find evidence for significant human diversity in TCRB variable gene alleles beyond what is currently represented in the IMGT database. TCRB sequencing using multiplex Framework 1 and Constant gene targeting primers is ideally suited for studying the role of TCRB polymorphism in autoimmune disease and immune-mediated adverse events during immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.5_suppl.129
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    Peripheral blood TCRB chain convergence and clonal expansion following cytomegalovirus infection: Implications for the biomarker use of TCR-seq.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 8_suppl ( 2019-03-10), p. 134-134
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 8_suppl ( 2019-03-10), p. 134-134
    Abstract: 134 Background: Human cytomegalovirus (CMV) is a common immune-evasive herpes family virus leading to lifelong asymptomatic infection in 50 to 80% of humans. The effect of CMV infection on the T cell repertoire may be relevant given interest in identifying T cell repertoire features predictive of response to checkpoint blockade immunotherapy (CPI) for cancer. Here we sought to identify features of CMV infection using TCRB profiling of peripheral blood (PBL) total RNA. Methods: Total RNA from PBL was obtained from 35 blood donors of known CMV status, then used for TCRB sequencing via the Oncomine TCRB-LR assay (amplicon spanning CDR1, 2 and 3) and the Ion Torrent S5. In parallel, we prepared libraries via the Oncomine TCRB-SR assay (CDR3 only). Data were used to identify TCRB repertoire features correlated with CMV status and compare repertoire features across the two assays. Results: T cell clone evenness was reduced in CMV positive individuals irrespective of age, predictive of CMV status (AUC = .86, p = 2E-4, Wilcoxon), and strongly correlated between LR and SR assays (Spearman cor = .96). TCR convergence was elevated in CMV positive individuals and uncorrelated with evenness (Spearman cor = -.03) such that the combination of convergence and evenness improved the performance of a logistic regression classifier (AUC = .93). Conclusions: We identify reduced T cell evenness and elevated TCR convergence as features of chronic CMV infection. CMV infection appears to significantly alter the T cell repertoire, suggesting that CMV status may be required for proper interpretation of T cell expansion in the context of CPI for cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.8_suppl.134
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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