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An Interpretive Approach to Two Wind Partitas of Franz Vincent Krommer: Partita in F, Op. 57 (1808) and Partita in E-flat, Op. 79 (1810), A Lecture Recital : Together with Three Recitals of Selected Works of Stravinsky, Hanson, Martin Mailman, Holst and Walton
Get PDFAn interpretive approach to performing two works by Franz Krommer for wind ensemble. Including a short history of Harmoniemusik, with origins, development, and chronology of the instruments and repertoire, the roles of "better-known" composers of Harmoniemusik, and its importance in both general music history and history of the wind band. An account of known biographical detail concerning Franz Krommer, his life, his musical involvement and career in Europe, and his place in music history. An overview of his compositions for wind groups other than the Harmoniemusik, including his symphonic music and concertos. Detailed analyses of the two octet-partitas, Partita in F, Op. 57 and Partita in E-flat, Op. 79, with discussion of thematic, harmonic, melodic, articulation, and formal characteristics illustrated through score examples. Examination of issues for a conductor to consider when approaching a performance of these works such as instrumentation (modern vs. period instruments, selecting 16-foot instrument), taking (or not taking) repeats with respect to form, interpreting articulations, determining metronomic tempos, ensemble balance, and style based on wind music of the Classical period. Also, how this music can (and why it should) be used by wind conductors as both a teaching supplement and a compositional model for pieces from the Classical period. Conclusion includes a call for further research on Krommer and his works
(+)-Dinapsoline: An Efficient Synthesis and Pharmacological Profile of a Novel Dopamine Agonist
No full textA highly convergent synthesis was developed for the novel dopamine agonist dinapsoline (12)
(Ghosh, D.; Snyder, S. E.; Watts, V. J.; Mailman, R. B.; Nichols, D. E. 8,9-Dihydroxy-2,3,7,
11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline: A Potent Full Dopamine D1 Agonist Containing
a Rigid β-Phenyldopamine Pharmacophore. J. Med. Chem. 1996, 39 (2), 549−555). The crucial
step in the new synthesis was a free radical-initiated cyclization to give the complete dinapsoline
framework. The improved synthesis required half as many steps as the original procedure
(Nichols, D. E.; Mailman, R.; Ghosh, D. Preparation of novel naphtho[1,2,3-de]isoquinolines
as dopamine receptor ligands. PCT Int. Appl. WO 9706799 A1, Feb 27, 1997). One of the late-stage intermediates (11) was resolved into a pair of enantiomers. From there, the (R)-(+)-12
(absolute configuration by X-ray) of dinapsoline was identified as the active enantiomer. In
unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats, (+)-dinapsoline showed robust rotational
behavior comparable to that of an external benchmark, trans-4,5,5a,6,7,11b-hexahydro-2-propyl-benzo[f]thieno[2,3-c]quinoline-9,10-diol, hydrochloride 18 (Michaelides, M. R.; Hong, Y. Preparation of heterotetracyclic compounds as dopamine agonists. PCT Int. Appl. WO 9422858 A1,
Oct 13, 1994)
OMIA (Online Mendelian Inheritance in Animals): an enhanced platform and integration into the Entrez search interface at NCBI
No full textOnline Mendelian Inheritance in Animals (OMIA) is a comprehensive, annotated catalogue of inherited dis-orders and other familial traits in animals other than humans and mice. Structured as a comparative bio-logy resource, OMIA is a comprehensive resource of phenotypic information on heritable animal traits and genes in a strongly comparative context, relating traits to genes where possible. OMIA is modelled on and is complementary to Online Mendelian Inher-itance in Man (OMIM). OMIA has been moved to a MySQL database at the Australian National Genomic Information Service (ANGIS) and can be accessed a
Education 2.0? Designing the web for teaching and learning: A Commentary by the Technology Enhanced Learning phase of the Teaching and Learning Research Programme
Get PDFB-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial
No full textAmbient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5–induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.Version of Recor
Quantifying single nucleotide variant detection sensitivity in exome sequencing
Get PDFBACKGROUND: The targeted capture and sequencing of genomic regions has rapidlydemonstrated its utility in genetic studies. Inherent in this technology isconsiderable heterogeneity of target coverage and this is expected tosystematically impact our sensitivity to detect genuine polymorphisms. To fullyinterpret the polymorphisms identified in a genetic study it is often essentialto both detect polymorphisms and to understand where and with what probabilityreal polymorphisms may have been missed.RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set ofgold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to theprobability of calling the correct genotype at that site. We find that measuredsensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us toproduce single nucleotide resolution SNV sensitivity estimates which can bemerged to give summary sensitivity measures for any arbitrary partition of thetarget sequences (nucleotide, exon, gene, pathway, exome). These metrics aredirectly comparable between platforms and can be combined between samples to give"power estimates" for an entire study. We estimate a local read depth of 13X isrequired to detect the alleles and genotype of a heterozygous SNV 95% of thetime, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X,commonly used for rare disease exome sequencing studies, we predict 5-15% ofheterozygous and 1-4% of homozygous SNVs in the targeted regions will be missed.CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chanceof being missed when commonly applied read coverage thresholds are used despitethe widely held assumption that there is good polymorphism detection at thesecoverage levels. Such alleles are likely to be of functional importance inpopulation based studies of rare diseases, somatic mutations in cancer andexplaining the "missing heritability" of quantitative traits.<br/
CellML: Cellml.org, Tools and Community
No full textPoster presented at ICSB2007The purpose of CellML is to store and exchange computer-based mathematical models of as wide a
range of scale and subject as posssible. For example, biochemical signalling and metabolic systems
can be embedded in electrophysiological models of excitable cells in CellML. The CellML language
is an open standard based on the XML markup language and is being developed by the
Bioengineering Institute at the University of Auckland and affiliated research groups [1].
The majority of computational biology publications aim to discuss their model but often fail to
provide a comprehensive set of instructions for recreating the model, or include errors preventing
reproduction of published model outputs. Publishing a paper with a link to a CellML model facilitates
the wide distribution and recreation of that model, and additionally forces the modeller to carefully
consider matters such as unit consistency.
The CellML specification and application programming interfaces (API) are driven by a core team,
but a growing international community is involved in work related to CellML. A community website
(www.cellml.org) has been set up as a focal point for the community and also functions as a model
repository. A number of groups are developing software tools for CellML and using the language for
research in computational biology.
A repository of almost 300 unique CellML models is available at www.cellml.org/models: these are
computational models from peer-reviewed publications that have been coded into CellML. These
models are undergoing an active curation process based on the MIRIAM standard, proposed by the
international biological modelling community [2]. This process includes provision of comprehensive
documentation, annotation with citation and model author metadata, maintenance of file modification
histories, and correspondence with model authors to ensure that models define all required initial
conditions and parameters. The CellML community strongly supports collaboration with other groups
to continue to set standards for curation and distribution of biological models.
A number of free / open source software tools for developing and simulating CellML models are
available, including Physiome CellML Environment (PCEnv) and Cellular Open Resource (COR).
Other modelling environments such as JSim and Virtual Cell also support the CellML format.
Information on further tools such as validators, debuggers and simulation specific packages can be
found at www.cellml.org/tools.
In the near future, models in the cellml.org model repository will be completely annotated with
ontologies such as BioPaX and references to databases such as UniProt. Models will be broken down
into the components from which they are comprised, and these components will themselves be
curated, providing a toolbox of standardised computational parts from which new models can be
created, in an in silico analogy to the MIT Registry of Standard Biological parts
(http://parts.mit.edu/registry/index.php/Main_Page). An API has recently been developed for
software tools to allow interaction between CellML and SVG diagrams of models, such as
biochemical pathway schematics, and work is also underway to standardise graphical representations
of CellML models.
For more information, please join the CellML community mailing list at
http://www.cellml.org/mailman/listinfo/cellml-discussion.
1.) Cuellar, A.A., Lloyd, C. M., Nielsen, P. F., Bullivant, D. P., Nickerson, D. P., Hunter, P. J. "An
Overview of CellML 1.1, a Biological Model Description Language" Simulation, 2003, 79, No. 12,
740-747
2.) Le Novere, N., Finney, A., Hucka, M., Bhalla, U.S., Campagne, F., Collado-Vides, J., Crampin,
E.J., Halstead, M., Klipp, E., Mendes, P., Nielsen, P., Sauro, H., Shapiro, B., Snoep, J.L., Spence,
H.D., Wanner, B.L. "Minium information requested in the annotation of biochemical models
(MIRIAM)" Nature Biotechnology, 2005, 23 1509-151
Ambient temperature and cardiovascular biomarkers in a repeated-measure study in healthy adults: A novel biomarker index approach
No full textBackground: Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and -endothelial function may be the mechanistic pathways associated with ambient temperature. Methods: Forty study participants underwent repeated blood collections for 12 times in Beijing, China in 2010-2011. Ambient temperature and air pollution data were measured in central monitors close to student residences. We created five indices as the sum of weighted biomarker percentiles to represent the overall levels of 15 cardiovascular biomarkers in five pathways (systemic inflammation: hs-CRP, TNF-alpha and fibrinogen; coagulation: fibrinogen, PAI-1, tPA, vWF and sP-selectin; systemic oxidative stress: Ox-LDL and sCD36: antioxidant activity: EC-SOD and GPX1; and endothelial function: ET-1, E-selectin, ICAM-1 and VCAM-1). We used generalized mixed-effects models to estimate temperature effects controlling for air pollution and other covariates. Results: There were significant decreasing trends in the adjusted means of biomarker indices over the lowest to the highest quartiles of daily temperatures before blood collection. A 10 degrees C decrease at 2-d average daily temperature were associated with increases of 2.5% [95% confidence interval (CI): 0.7, 4.2], 1.6% (95% CI: 0.1, 3.1), 2.7% (95% CI: 0.5, 4.8), 5.5% (95% CI: 3.8, 7.3) and 2.0% (95% CI: 0.3, 3.8) in the indices for systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function, respectively. In contrast, the associations between ambient temperature and individual biomarkers had substantial variation in magnitude and strength. Conclusions: The altered cardiovascular biomarker profiles in healthy adults associated with ambient temperature changes may help explain the temperature-related cardiovascular morbidity and mortality. The biomarker index approach may serve as a novel tool to capture ambient temperature effects.National Natural Science Foundation of China [91543112, 81072267]; Beijing Municipal Commission of Education [20131000109]; Peking University Health Science Center [BMU20160549]SCI(E)ARTICLE231-23815
