Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.

Conference scene: Immune signatures in the tumor and beyond.

Led by key opinion leaders in the field, the Cancer Immunotherapy Consortium of the Cancer Research Institute 2012 Scientific Colloquium included 179 participants who exchanged cutting-edge information on basic, clinical and translational cancer immunology and immunotherapy. The meeting revealed how rapidly this field is advancing. The keynote talk was given by Wolf H Fridman and it described the microenvironment of primary and metastatic human tumors. Participants interacted through oral presentations and panel discussions on topics that included host reactions in tumors, advances in imaging, monitoring therapeutic immune modulation, the benefit and risk of immunotherapy, and immune monitoring activities. In summary, the annual meeting gathered clinicians and scientists from academia, industry and regulatory agencies from around the globe to interact and exchange important scientific advances related to tumor immunobiology and cancer immunotherapy.

Combined clonotyping and gene signatures of individual tumor-reactive CD8 T-cells define their functional relevance following peptide vaccination in melanoma patients

Novel cancer vaccines are capableto efficiently induce and boost humantumor antigen specific T-cells. However,the properties of these CD8T-cells are only partially characterized.For in depth investigation ofT-cells following Melan-A/MART-1peptide vaccination in melanoma patients,we conducted a detailed prospectivestudy at the single cell level.We first sorted individual human naiveand effector CD8 T-cells from peripheralblood by flow cytometry, andtested a modified RT-PCR protocolincluding a global amplification ofexpressed mRNAs to obtain sufficientcDNAfromsingle cells.We successfullydetected the expression ofseveral specific genes of interest evendown to 106-fold dilution (equivalentto 10-5 cell). We then analyzed tumor-specific effector memory (EM)CD8T-cell subpopulations ex vivo, assingle cells from vaccinated melanomapatients. To elucidate the hallmarksof effective immunity the genesignatures were defined by a panel ofgenes related to effector functions(e.g. IFN-, granzyme B, perforin),and individual clonotypes were identifiedaccording to the expression ofdistinct T-cell receptors (TCR). Usingthis novel single cell analysis approach,we observed that T-cell differentiationis clonotype dependent,with a progressive restriction in TCRBV clonotype diversity from EMCD28pos to EMCD28neg subsets. However,the effector function gene imprintingis clonotype-independent,but dependent on differentiation,since it correlates with the subset oforigin (EMCD28pos or EMCD28neg). We also conducted a detailedcomparative analysis after vaccinationwith natural vs. analog Melan-Apeptide. We found that the peptideused for vaccination determines thefunctional outcome of individualT-cell clonotypes, with native peptideinducing more potent effector functions.Yet, selective clonotypic expansionwith differentiation was preservedregardless of the peptide usedfor vaccination. In summary, the exvivo single cell RT-PCR approach ishighly sensitive and efficient, andrepresents a reliable and powerfultool to refine our current view of molecularprocesses taking place duringT-cell differentiation.

Essai sur l'origine de la gravure en bois et en taille-douce, et sur la connoissance des estampes des XVe et XVIe siècles, où il est parlé aussi de l'origine des cartes à jouer et des cartes géographiques. Tome 2 / , suivi de Recherches sur l'origine du papier de coton et de lin, sur la calligraphie depuis les plus anciens temps jusqu'à nos jours, sur les miniatures des anciens manuscrits, sur les filigranes des papiers des XIVe, XVe et XVIe siècles, ainsi que sur l'origine et le premier usage des signatures et des chiffres dans l'art de la typographie

Comprend : Mémoire sur l'origine et le premier usage des signatures et des chiffres dans l'art typographique ; Recherches sur l'origine et le premier usage des registres, des signatures, des réclames et des chiffres de page dans les livres imprimés ; Notice sur les éditions stéréotypes

Essai sur l'origine de la gravure en bois et en taille-douce, et sur la connoissance des estampes des XVe et XVIe siècles, où il est parlé aussi de l'origine des cartes à jouer et des cartes géographiques. Tome 1 / , suivi de Recherches sur l'origine du papier de coton et de lin, sur la calligraphie depuis les plus anciens temps jusqu'à nos jours, sur les miniatures des anciens manuscrits, sur les filigranes des papiers des XIVe, XVe et XVIe siècles, ainsi que sur l'origine et le premier usage des signatures et des chiffres dans l'art de la typographie

Comprend : Mémoire sur l'origine et le premier usage des signatures et des chiffres dans l'art typographique ; Recherches sur l'origine et le premier usage des registres, des signatures, des réclames et des chiffres de page dans les livres imprimés ; Notice sur les éditions stéréotypes

Album amicorum Chunradi Kechleri. II y a surtout des signatures recueillies à Bourges en 1584 et 1585

Gaignières.

Arrêt du grand conseil portant réglement pour les banquiers expéditionnaires et les signatures de cour de Rome

[Acte. 1725-03-27. Paris]

Album amicorum Jo. Huenich, Anthuerpiani. Ce volume renferme surtout des signatures recueillies à Constantinople en 1586.

Fonds non déterminé.

St. Catharines Public Schools Honor Pupils certificate to Bessie Bell, December 1910.

A St. Catharines Public Schools Honor Pupils certificate presented to Bessie Bell, dated December 8, 1910 and signed by G. E. Lounsbury, Teacher. This certificate was in the possession of the Richard Bell Family of St. Catharines, Ontario.The certificate reads: "Bessie Bell is this day entitled to receive this public expression of approbation for Industry, Good Conduct and Regular Attendance, for the week ending December 8th 1910. Parents are particularly requested to enquire for a card of this kind at the close of each week."

Electrical Development Company of Ontario certificate of stock ownership, ca. 1910.

The Electrical Development Company of Ontario was created in 1903. It was one of three private power companies that had water power leases with the Niagara Parks Commission, but was the only one that was financed with Canadian capital. The company built the Toronto Power Generating Station at Niagara Falls beginning in 1906, and the power house was completed in 1913. During the construction, there was much debate about whether the utility should remain privately operated or become a public utility. In 1920, the company became part of the public utility.

Marriage Certificate - Charles Nickles & Margaret Nelles

A marriage license for "Charles Nickles of the Township of Grimsby Gentleman and Margaret Nelles of Same place Spinster" and is dated 23 July, 1831.

Entrance Examination Certificate Collegiate Institutes and High Schools of Ontario - Mary Willson

A certificate from the Collegiate Institutes and High Schools of Ontario of the Education Department of Ontario stating: "It is hereby certified that Mary Willson has passed the entrance examination required by the Education Department for admission to a Collegiate Institute or High School. Dated at Welland August 1st, 1908. Signed John W. Marshall, B.A. Inspector of Public Schools.

Certificate of Membership United Empire Loyalists Association of Canada

A certificate that Francis Bond Head Wilson "being of United Empire Loyalist Descent has been regularly proposed, balloted for, and elected a member of this association." It is dated September 14th, 1934.

Marriage Certificate - Thomas Cowan & Annie Easling, 1884

A marriage certificate for Thomas Cowan of Thorold and Annie Easling of St. Catharines. The certificate is dated October 8, 1884 and is witnessed by W. Ross and Jennie McElroy.