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This book is aimed at the practicing academic librarian, especially those working on the ?front lines? of reference, instruction, collection development, and other capacities that involve dealing directly with library patrons in a time of changing scholarly communication paradigms. The book looks at open access from the perspective of a practicing academic librarian and challenges fellow librarians to continue the dialogue about how the movement might be affecting day-to-day library work and the future of academic libraries. Written by a practicing academic librarian with many years experience in reference, as well as in collection development and faculty liaison roles Written with the ?front-line” academic librarian in mind from a practical point of view Contains numerous references to refer the reader to many open access resources; includes extensive footnotes for further reading

This book is aimed at the practicing academic librarian, especially those working on the ?front lines? of reference, instruction, collection development, and other capacities that involve dealing directly with library patrons in a time of changing scholarly communication paradigms. The book looks at open access from the perspective of a practicing academic librarian and challenges fellow librarians to continue the dialogue about how the movement might be affecting day-to-day library work and the future of academic libraries. Written by a practicing academic librarian with many years experience in reference, as well as in collection development and faculty liaison roles Written with the ?front-line” academic librarian in mind from a practical point of view Contains numerous references to refer the reader to many open access resources; includes extensive footnotes for further reading

This book is aimed at the practicing academic librarian, especially those working on the ?front lines? of reference, instruction, collection development, and other capacities that involve dealing directly with library patrons in a time of changing scholarly communication paradigms. The book looks at open access from the perspective of a practicing academic librarian and challenges fellow librarians to continue the dialogue about how the movement might be affecting day-to-day library work and the future of academic libraries. Written by a practicing academic librarian with many years experience in reference, as well as in collection development and faculty liaison roles Written with the ?front-line” academic librarian in mind from a practical point of view Contains numerous references to refer the reader to many open access resources; includes extensive footnotes for further reading

This book is aimed at the practicing academic librarian, especially those working on the ?front lines? of reference, instruction, collection development, and other capacities that involve dealing directly with library patrons in a time of changing scholarly communication paradigms. The book looks at open access from the perspective of a practicing academic librarian and challenges fellow librarians to continue the dialogue about how the movement might be affecting day-to-day library work and the future of academic libraries. Written by a practicing academic librarian with many years experience in reference, as well as in collection development and faculty liaison roles Written with the ?front-line” academic librarian in mind from a practical point of view Contains numerous references to refer the reader to many open access resources; includes extensive footnotes for further reading

This book is aimed at the practicing academic librarian, especially those working on the ?front lines? of reference, instruction, collection development, and other capacities that involve dealing directly with library patrons in a time of changing scholarly communication paradigms. The book looks at open access from the perspective of a practicing academic librarian and challenges fellow librarians to continue the dialogue about how the movement might be affecting day-to-day library work and the future of academic libraries. Written by a practicing academic librarian with many years experience in reference, as well as in collection development and faculty liaison roles Written with the ?front-line” academic librarian in mind from a practical point of view Contains numerous references to refer the reader to many open access resources; includes extensive footnotes for further reading

BackgroundAccurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies.ResultsCell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300×. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease.ConclusionsOur cell-line titration series dataset, along with the associated verification results, was effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development. The data is available for further analysis at the European Genome-phenome Archive under accession number EGAS00001001016. Data access requires registration through the International Cancer Genome Consortium's Data Access Compliance Office (ICGC DACO).

BackgroundAccurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies.ResultsCell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300×. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease.ConclusionsOur cell-line titration series dataset, along with the associated verification results, was effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development. The data is available for further analysis at the European Genome-phenome Archive under accession number EGAS00001001016. Data access requires registration through the International Cancer Genome Consortium's Data Access Compliance Office (ICGC DACO).

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

Suppressors of cytokine signalling (SOCS) protein induction via the "Janus kinase- signal transducer and activator of transcription" (JAK-STAT) pathway has been shown to be a critical negative feedback mechanism that prevents inappropriately sustained signalling from activated cytokine receptors. It also provides a mechanism by which other signalling modules could potentially regulate the JAK-STAT pathway. In this study, I have demonstrated that elevation of the prototypical second messenger cyclic AMP (cAMP) is capable of promoting the time- and concentration-dependent accumulation of the SOCS-3 isoform in U937 human promyeloid cells and HL60 human promyoblast cells. Experiments with MG132 demonstrated that cAMP specifically promoted SOCS-3 synthesis rather than blocking its degradation by the proteasome. The accumulation of SOCS-3 in U937 cells correlated with a reduced ability of the granulocyte-colony stimulating factor (G-CSF) receptor, which is a bona fide target for SOCS-3 in vivo, to promote the Tyr phosphorylation of STAT3 and the dual Thr/Tyr phosphorylation of ERK, suggesting that the cAMP-mediated accumulation of SOCS-3 is sufficient to suppress JAK-STAT pathway activation by this receptor. Further characterisation of the response demonstrated that SOCS-3 induction could not be blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA), suggesting that a PKA independent mechanism was responsible. Consistent with this hypothesis, selective activation of PKA with the selective cAMP analogue 6Be-cAMP failed to promote SOCS-3 accumulation. Surprisingly, selective activation of "Exchange protein activated by cAMP" (Epac), a recently identified PKA-independent intracellular sensor of cAMP, using the cAMP analogue 8pCPT- 20Me-cAMP also failed to promote SOCS-3 accumulation. Moreover, the inability of both 6Be-cAMP and 8pCPT-20Me-cAMP to promote SOCS-3 accumulation was not due to a lack of biological activity, since both were able to stimulate the phosp

Suppressors of cytokine signalling (SOCS) protein induction via the "Janus kinase- signal transducer and activator of transcription" (JAK-STAT) pathway has been shown to be a critical negative feedback mechanism that prevents inappropriately sustained signalling from activated cytokine receptors. It also provides a mechanism by which other signalling modules could potentially regulate the JAK-STAT pathway. In this study, I have demonstrated that elevation of the prototypical second messenger cyclic AMP (cAMP) is capable of promoting the time- and concentration-dependent accumulation of the SOCS-3 isoform in U937 human promyeloid cells and HL60 human promyoblast cells. Experiments with MG132 demonstrated that cAMP specifically promoted SOCS-3 synthesis rather than blocking its degradation by the proteasome. The accumulation of SOCS-3 in U937 cells correlated with a reduced ability of the granulocyte-colony stimulating factor (G-CSF) receptor, which is a bona fide target for SOCS-3 in vivo, to promote the Tyr phosphorylation of STAT3 and the dual Thr/Tyr phosphorylation of ERK, suggesting that the cAMP-mediated accumulation of SOCS-3 is sufficient to suppress JAK-STAT pathway activation by this receptor. Further characterisation of the response demonstrated that SOCS-3 induction could not be blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA), suggesting that a PKA independent mechanism was responsible. Consistent with this hypothesis, selective activation of PKA with the selective cAMP analogue 6Be-cAMP failed to promote SOCS-3 accumulation. Surprisingly, selective activation of "Exchange protein activated by cAMP" (Epac), a recently identified PKA-independent intracellular sensor of cAMP, using the cAMP analogue 8pCPT- 20Me-cAMP also failed to promote SOCS-3 accumulation. Moreover, the inability of both 6Be-cAMP and 8pCPT-20Me-cAMP to promote SOCS-3 accumulation was not due to a lack of biological activity, since both were able to stimulate the phosp

Suppressors of cytokine signalling (SOCS) protein induction via the "Janus kinase- signal transducer and activator of transcription" (JAK-STAT) pathway has been shown to be a critical negative feedback mechanism that prevents inappropriately sustained signalling from activated cytokine receptors. It also provides a mechanism by which other signalling modules could potentially regulate the JAK-STAT pathway. In this study, I have demonstrated that elevation of the prototypical second messenger cyclic AMP (cAMP) is capable of promoting the time- and concentration-dependent accumulation of the SOCS-3 isoform in U937 human promyeloid cells and HL60 human promyoblast cells. Experiments with MG132 demonstrated that cAMP specifically promoted SOCS-3 synthesis rather than blocking its degradation by the proteasome. The accumulation of SOCS-3 in U937 cells correlated with a reduced ability of the granulocyte-colony stimulating factor (G-CSF) receptor, which is a bona fide target for SOCS-3 in vivo, to promote the Tyr phosphorylation of STAT3 and the dual Thr/Tyr phosphorylation of ERK, suggesting that the cAMP-mediated accumulation of SOCS-3 is sufficient to suppress JAK-STAT pathway activation by this receptor. Further characterisation of the response demonstrated that SOCS-3 induction could not be blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA), suggesting that a PKA independent mechanism was responsible. Consistent with this hypothesis, selective activation of PKA with the selective cAMP analogue 6Be-cAMP failed to promote SOCS-3 accumulation. Surprisingly, selective activation of "Exchange protein activated by cAMP" (Epac), a recently identified PKA-independent intracellular sensor of cAMP, using the cAMP analogue 8pCPT- 20Me-cAMP also failed to promote SOCS-3 accumulation. Moreover, the inability of both 6Be-cAMP and 8pCPT-20Me-cAMP to promote SOCS-3 accumulation was not due to a lack of biological activity, since both were able to stimulate the phosp

Suppressors of cytokine signalling (SOCS) protein induction via the "Janus kinase- signal transducer and activator of transcription" (JAK-STAT) pathway has been shown to be a critical negative feedback mechanism that prevents inappropriately sustained signalling from activated cytokine receptors. It also provides a mechanism by which other signalling modules could potentially regulate the JAK-STAT pathway. In this study, I have demonstrated that elevation of the prototypical second messenger cyclic AMP (cAMP) is capable of promoting the time- and concentration-dependent accumulation of the SOCS-3 isoform in U937 human promyeloid cells and HL60 human promyoblast cells. Experiments with MG132 demonstrated that cAMP specifically promoted SOCS-3 synthesis rather than blocking its degradation by the proteasome. The accumulation of SOCS-3 in U937 cells correlated with a reduced ability of the granulocyte-colony stimulating factor (G-CSF) receptor, which is a bona fide target for SOCS-3 in vivo, to promote the Tyr phosphorylation of STAT3 and the dual Thr/Tyr phosphorylation of ERK, suggesting that the cAMP-mediated accumulation of SOCS-3 is sufficient to suppress JAK-STAT pathway activation by this receptor. Further characterisation of the response demonstrated that SOCS-3 induction could not be blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA), suggesting that a PKA independent mechanism was responsible. Consistent with this hypothesis, selective activation of PKA with the selective cAMP analogue 6Be-cAMP failed to promote SOCS-3 accumulation. Surprisingly, selective activation of "Exchange protein activated by cAMP" (Epac), a recently identified PKA-independent intracellular sensor of cAMP, using the cAMP analogue 8pCPT- 20Me-cAMP also failed to promote SOCS-3 accumulation. Moreover, the inability of both 6Be-cAMP and 8pCPT-20Me-cAMP to promote SOCS-3 accumulation was not due to a lack of biological activity, since both were able to stimulate the phosp

Suppressors of cytokine signalling (SOCS) protein induction via the "Janus kinase- signal transducer and activator of transcription" (JAK-STAT) pathway has been shown to be a critical negative feedback mechanism that prevents inappropriately sustained signalling from activated cytokine receptors. It also provides a mechanism by which other signalling modules could potentially regulate the JAK-STAT pathway. In this study, I have demonstrated that elevation of the prototypical second messenger cyclic AMP (cAMP) is capable of promoting the time- and concentration-dependent accumulation of the SOCS-3 isoform in U937 human promyeloid cells and HL60 human promyoblast cells. Experiments with MG132 demonstrated that cAMP specifically promoted SOCS-3 synthesis rather than blocking its degradation by the proteasome. The accumulation of SOCS-3 in U937 cells correlated with a reduced ability of the granulocyte-colony stimulating factor (G-CSF) receptor, which is a bona fide target for SOCS-3 in vivo, to promote the Tyr phosphorylation of STAT3 and the dual Thr/Tyr phosphorylation of ERK, suggesting that the cAMP-mediated accumulation of SOCS-3 is sufficient to suppress JAK-STAT pathway activation by this receptor. Further characterisation of the response demonstrated that SOCS-3 induction could not be blocked by H89, an inhibitor of cAMP-dependent protein kinase (PKA), suggesting that a PKA independent mechanism was responsible. Consistent with this hypothesis, selective activation of PKA with the selective cAMP analogue 6Be-cAMP failed to promote SOCS-3 accumulation. Surprisingly, selective activation of "Exchange protein activated by cAMP" (Epac), a recently identified PKA-independent intracellular sensor of cAMP, using the cAMP analogue 8pCPT- 20Me-cAMP also failed to promote SOCS-3 accumulation. Moreover, the inability of both 6Be-cAMP and 8pCPT-20Me-cAMP to promote SOCS-3 accumulation was not due to a lack of biological activity, since both were able to stimulate the phosp