LP Recordings of Traditional Newfoundland Music

Michael Taft parle de la musique traditionnelle de Terre-Neuve enregistrée sur disques LP actuellement sur le marché, en donnant des détails sur les différences de style et de présentation des divers chanteurs, instrumentistes et groupements. Sa liste constitue également un supplément à celle des disques inclue dans la “Liste de références sur la Musique folklorique Canadienne” parue dans notre première publication

Dig-Songs: Parody, Caricature, and Reportage on an Archeological Site

Michael Taft décrit la manière de composer des chansons parodies ordinairement en usage parmi les étudiants en archéologie lorsqu’ils font l’excavation d’un site sur leur terrain de travail. Alors qu’ils utilisent comme modèles des chants populaires, ils incorporent dans leurs couplets des incidences et références ayant trait à leurs compagnons de travai

A yeast-based assay for protein tyrosine kinase substrate specificity and inhibitor resistance

Phosphorylation of tyrosines by protein kinases is a fundamental mode of signal transduction in all eukaryotic cells, leading to a wide variety of cellular outcomes, including proliferation, differentiation, transcriptional activation, and programmed cell death. Perturbations to tyrosine kinase signaling networks by activation, overexpression, or mutation is the driving factor in many diseases, most notably cancers. The development of tyrosine kinase inhibitors, 37 of which are currently FDA-approved, has led to a revolution in cancer treatment. Imatinib, the first FDA-approved kinase inhibitor, has drastically improved prognosis for patients with Bcr-abl-positive leukemias. Despite this unprecedented success, however, up to one-third of patients lose response to imatinib due to mutations within the tyrosine kinase domain of Bcr-abl. Subsequent generations of Bcr-abl inhibitors, including dasatinib and ponatinib, have been developed to overcome these resistance mutations, but in each case, novel resistance mutations have arisen. We present a high-throughput yeast-based assay for the prediction of dasatinib- and ponatinib-resistant mutations in the ABL1 kinase domain. Our results not only recapitulate all known dasatinib-resistant mutations, but confirm recent patient data emphasizing the importance of compound mutations in ponatinib resistance. Furthermore, with hundreds of kinase inhibitors in development for the treatment of a wide range of diseases, understanding the cellular pathway of each kinase is critically important to the selection of ideal drug targets and avoiding potentially toxic side effects. Discovery of novel tyrosine kinase substrates is hindered by the presence of 90 human tyrosine kinases, which are often active in the same pathways. Phosphoproteomics, chemical genetics, and in vitro assays have been used to great success, yet only 30% of phosphorylated tyrosines in the human proteome have been assigned to a specific kinase. Recent advances in predicting tyrosine kinase substrates have been made by combining large data sets on kinase domain specificity, cellular localization, and protein-protein interactions in probabilistic algorithms. However, the high-quality data sets required for accurate predictions are often lacking. In chapter 2, we present a high-throughput yeastbased assay for screening millions of putative kinase substrates, which we then use to build a probabilistic model to accurately predict the in vitro phosphorylation of candidate substratesBiochemistr

The Newfoundland Popular Music Project

Messieurs Posen et Taft, gradués en folklore au Memorial University, décrivent leur projet relatif à la musique populaire de Terre-Neuve. Ils ont compilé une liste de chansons enregistrées par des chanteurs Terreneuviens et des chants de Terre-Neuve enregistrés par des personnes étrangères; ils ont aussi interviewé un certain nombre d ’artistes préalablement enregistrés, cela faisant partie de l’étude en cours

Fault-Tolerant Coding for State Machines

Two reliable fault-tolerant coding schemes have been proposed for state machines that are used in field-programmable gate arrays and application-specific integrated circuits to implement sequential logic functions. The schemes apply to strings of bits in state registers, which are typically implemented in practice as assemblies of flip-flop circuits. If a single-event upset (SEU, a radiation-induced change in the bit in one flip-flop) occurs in a state register, the state machine that contains the register could go into an erroneous state or could hang, by which is meant that the machine could remain in undefined states indefinitely. The proposed fault-tolerant coding schemes are intended to prevent the state machine from going into an erroneous or hang state when an SEU occurs. To ensure reliability of the state machine, the coding scheme for bits in the state register must satisfy the following criteria: 1. All possible states are defined. 2. An SEU brings the state machine to a known state. 3. There is no possibility of a hang state. 4. No false state is entered. 5. An SEU exerts no effect on the state machine. Fault-tolerant coding schemes that have been commonly used include binary encoding and "one-hot" encoding. Binary encoding is the simplest state machine encoding and satisfies criteria 1 through 3 if all possible states are defined. Binary encoding is a binary count of the state machine number in sequence; the table represents an eight-state example. In one-hot encoding, N bits are used to represent N states: All except one of the bits in a string are 0, and the position of the 1 in the string represents the state. With proper circuit design, one-hot encoding can satisfy criteria 1 through 4. Unfortunately, the requirement to use N bits to represent N states makes one-hot coding inefficient

Continuous purification of cell culture-derived influenza A virus particles through pseudo- affinity membrane chromatography

Continuous manufacturing is a relevant trend in biopharmaceutical production to reduce the process footprint and to improve the process economy. Vaccines against world-spread diseases, such as influenza, should benefit in particular from such an approach, given the increasing demand for seasonal vaccines and the need for a fast response in case of a pandemic outbreak. Upstream processing of viral vaccines has seen important progress in continuous production of viral vaccines [1], which further supports the development of hybrid or fully continuous flow-schemes for downstream processing. Please click Additional Files below to see the full abstract

GenBase: A Complex Analytics Genomics Benchmark

This paper introduces a new benchmark, designed to test database management system (DBMS) performance on a mix of data management tasks (joins, filters, etc.) and complex analytics (regression, singular value decomposition, etc.) Such mixed workloads are prevalent in a number of application areas, including most science workloads and web analytics. As a specific use case, we have chosen genomics data for our benchmark, and have constructed a collection of typical tasks in this area. In addition to being representative of a mixed data management and analytics workload, this benchmark is also meant to scale to large dataset sizes and multiple nodes across a cluster. Besides presenting this benchmark, we have run it on a variety of storage systems including traditional row stores, newer column stores, Hadoop, and an array DBMS. We present performance numbers on all systems on single and multiple nodes, and show that performance differs by orders of magnitude between the various solutions. In addition, we demonstrate that most platforms have scalability issues. We also test offloading the analytics onto a coprocessor. The intent of this benchmark is to focus research interest in this area; to this end, all of our data, data generators, and scripts are available on our web site

Optimization of sulfated cellulose membrane adsorbers for the purification of influenza virus

The impact of influenza virus worldwide drives significant efforts and resources into R&D of vaccine manufacturing processes. A major challenge is to improve the flexibility of these processes, without substantially compromising productivity. As in other biotechnological processes, implementation of a chromatographic capturing step is favored since it removes the majority of the impurities (host cell proteins and DNA) and concentrates the product before polishing. Over the last years, significant efforts towards the development of sulfated membrane adsorbers were made. An improved membrane structure and the direct sulfation of a cellulose matrix resulted in a membrane adsorber (SCMA) with pseudo-affinity characteristics which can be used in the main chromatographic separation step for influenza virus. Pore size and ligand density are structural characteristics critical for the performance of the SCMA. For the best combination tested, the dynamic binding capacity (DBC) of the SCMA was shown to be 5.6×106 HAU/mlmembrane, which corresponds to an approximately 5.5 times higher capacity than bead-based media. However, both SCMA and bead-based media show a similar performance in terms of product recovery (86%-96%) and contaminant removal. Experimental results revealed the importance of operational parameters like virus concentration, flow rate, conductivity and elution salt concentration. Therefore, a DoE was used to determine the optimal process conditions in terms of product losses in the flow through as well as overall product yield and purity for an optimized SCMA using an influenza H1N1 virus strain. Currently undergoing experiments aim the identification of the best operating conditions, reevaluation of the DBC and purification performance of the optimized SCMA for the same virus strain. The robustness of the process for other virus (e.g. influenza H3N2 and B) is also being considered. Combining the advantages of a membrane chromatographic support with a chemical modification that is shown to be specific for the purification of influenza virus is a significant technological advance. After optimization of the SCMA and the respective operating conditions significant improvements in the influenza vaccine production process are to be expected