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"Sadowski, Michael"
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Portraits of promise : voices of successful immigrant students
\"By 2040, more than 30 percent of students in the United States will be immigrants or the children of immigrants. What factors can help these young people thrive in school, despite the many obstacles they face? And how can school staff best support immigrant students' academic and personal success? In Portraits of Promise, educators hear from the ultimate experts -- successful newcomer students. Drawing on the students' own stories, the book highlights the kinds of support and resources that help students engage positively with school culture, establish supportive peer networks, form strong bonds with teachers, manage competing expectations from home and school, and navigate the challenges of high-stakes testing and the college application process.\"--Publisher's description.
Harnessing QbD, Programming Languages, and Automation for Reproducible Biology
by
Sadowski, Michael I.
,
Grant, Chris
,
Fell, Tim S.
in
Automation
,
bioengineering
,
Bioengineering - methods
2016
Building robust manufacturing processes from biological components is a task that is highly complex and requires sophisticated tools to describe processes, inputs, and measurements and administrate management of knowledge, data, and materials. We argue that for bioengineering to fully access biological potential, it will require application of statistically designed experiments to derive detailed empirical models of underlying systems. This requires execution of large-scale structured experimentation for which laboratory automation is necessary. This requires development of expressive, high-level languages that allow reusability of protocols, characterization of their reliability, and a change in focus from implementation details to functional properties. We review recent developments in these areas and identify what we believe is an exciting trend that promises to revolutionize biotechnology.
Biological complexity is a barrier to fulfilling the potential of biotechnology.
Large numbers of complex experiments are required to overcome this barrier.
Performing such complex experiments requires sophisticated software and hardware.
New programming languages and software tools for this are developing quickly.
Low-cost automation and sensors promise to unlock these techniques for all.
Journal Article
JSA by Geoff Johns
\"Three generations of crime-fighters join together for the greater good: Sentinel, Wildcat, the Flash, Black Canary, Starman, Sand, Hourman, Atom Smasher, the Star-Spangled Kid and Hawkgirl. The heroes of the present and legends of the past come together to form the Justice Society of America! They have been called upon to save one of their own from one of the darkest powers ever to walk this earth... Celebrated comics writer Geoff Johns began his career here, as he mixed in younger, edgier characters with the elder statesmen of superheroes to create one of the standout DC Comics series in the 2000s.\"-- Provided by publisher.
Structural Constraints on the Covariance Matrix Derived from Multiple Aligned Protein Sequences
by
Sadowski, Michael I.
,
Taylor, William R.
in
Amino Acid Sequence
,
Amino Acids - metabolism
,
Biology
2011
Residue contact predictions were calculated based on the mutual information observed between pairs of positions in large multiple protein sequence alignments. Where previously only the statistical properties of these data have been considered important, we introduce new measures to impose constraints that make the contact map more consistent with a three dimensional structure. These included global (bulk) properties and local secondary structure properties. The latter allowed the contact constraints to be employed at the level of filtering pairs of secondary structure contacts which led to a more efficient (lower-level) implementation in the PLATO structure prediction server. Where previously the measure of success with this method had been whether the correct fold was predicted in the top 10 ranked models, with the current implementation, our summary statistic is the number of correct folds included in the top 10 models--which is on average over 50 percent.
Journal Article
Genome-Wide Analysis of Repressor Element 1 Silencing Transcription Factor/Neuron-Restrictive Silencing Factor (REST/NRSF) Target Genes
by
Sadowski, Michael I.
,
Donaldson, Ian J.
,
Chapman, Michael
in
Animals
,
Base Sequence
,
Binding sites
2004
The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding of these sequences and their trans-acting factors is required. Herein we have used a combined in silico and biochemical approach to identify binding sites [repressor element 1/neuron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and Fugu rubripes genomes. We have used this genome-wide analysis to identify 1,892 human, 1,894 mouse, and 554 Fugu RE1/NRSEs and present their location and gene linkages in a searchable database. Furthermore, we identified an in vivo hierarchy in which distinct subsets of RE1/NRSEs interact with endogenous levels of REST/NRSF, whereas others function as bona fide transcriptional control elements only in the presence of elevated levels of REST/NRSF. These data show that individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. This combined bioinformatic and biochemical approach serves to illustrate the selective manner in which a transcription factor interacts with its potential binding sites and regulates target genes. In addition, this approach provides a unique whole-genome map for a given transcription factor-binding site implicated in establishing specific patterns of neuronal gene expression.
Journal Article
Analytic Markovian Rates for Generalized Protein Structure Evolution
by
Sadowski, Michael I.
,
MacDonald, James T.
,
Coluzza, Ivan
in
Analysis
,
Biology
,
Computer Science
2012
A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the sub-space of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, in this work we present a model for constrained evolutionary trajectories represented by a markovian process throughout a set of protein-like structures artificially constructed to be topological intermediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. By using a coarse-grained representation for the protein structures, we derive an analytic formulation of the transition rates between each of the intermediate structures. The results indicate that compact structures with a high number of hydrogen bonds are more probable and have a higher likelihood to arise during evolution. Knowledge of the transition rates allows for the study of complex evolutionary pathways represented by trajectories through a set of intermediate structures.
Journal Article
implications of alternative splicing in the ENCODE protein complement
by
Reymond, Alexandre
,
Ólason, Páll ĺsólfur
,
Kai, Wang
in
Alternative Splicing
,
Biological Sciences
,
complement
2007
Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.
Journal Article
Prediction of protein contacts from correlated sequence substitutions
by
TAYLOR, WILLIAM R.
,
SADOWSKI, MICHAEL I.
in
Algorithms
,
Amino Acid Motifs
,
Amino acid sequence
2013
Recent work has led to a substantial improvement in the accuracy of predictions of contacts between amino acids using evolutionary information derived from multiple sequence alignments. Where large numbers of diverse sequence relatives are available and can be aligned to the sequence of a protein of unknown structure, it is now possible to generate high-resolution models without recourse to the structure of a template. In this review, we describe these exciting new techniques and critically assess the state of the art in contact prediction in light of them. We discuss areas for immediate research and development as well as potential future developments.
Journal Article
Identifying new variation at the J locus, previously identified as e6, in long juvenile ‘Paranagoiana’ soybean
2021
Key messageA previously identified soybean maturity locus, E6, is discovered to be J, with the long juvenile allele in Paranagoiana now deemed j−x.Soybean grown at latitudes of ~20° or lower can produce lower grain yields due to the short days. This limitation can be overcome by using the long juvenile trait (LJ) which delays flowering under short day conditions. Two LJ loci have been mapped to the same location on Gm04, J and E6. The objective of this research was to investigate the e6 allele in ‘Paranagoiana’ and determine if E6 and J are the same locus or linked loci. KASP markers showed that e6 lines did not have the j−1 allele of LJ PI 159925. A population fixed for E1 but segregating for E6, with e6 introgressed from Paranagoiana, showed single gene control for flowering and maturity under short days. Sequencing Glyma.04G050200, the J gene, with long amplification Taq found that the e6 line ‘Paranagoiana’ contains a Ty1-copia retrotransposon of ~10,000 bp, inserted within exon 4. PCR amplification of the cDNA of Glyma.04G050200 also showed differences between the mRNA sequences (presence of insertion in j−x). Hence, we conclude that the loci E6 and J are one locus and deem this new variation found in Paranagoiana as j−x.
Journal Article
An automatic method for assessing structural importance of amino acid positions
2009
Background
A great deal is known about the qualitative aspects of the sequence-structure relationship, for example that buried residues are usually more conserved between structurally similar homologues, but no attempts have been made to quantitate the relationship between evolutionary conservation at a sequence position and change to global tertiary structure. In this paper we demonstrate that the Spearman correlation between sequence and structural change is suitable for this purpose.
Results
Buried residues, bends, cysteines, prolines and leucines were significantly more likely to occupy positions highly correlated with structural change than expected by chance. Some buried residues were found to be less informative than expected, particularly residues involved in active sites and the binding of small molecules.
Conclusion
The correlation-based method generates predictions of structural importance for superfamily positions which agree well with previous results of manual analyses, and may be of use in automated residue annotation piplines. A PERL script which implements the method is provided.
Journal Article