A5084971613- Logic, programming, and type systems
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Formal Methods in Verification
- Logic, Reasoning, and Knowledge
- RNA modifications and cancer
- Parallel Computing and Optimization Techniques
- Sphingolipid Metabolism and Signaling
- Software Engineering Research
- Security and Verification in Computing
- Ruminant Nutrition and Digestive Physiology
- Pasture and Agricultural Systems
- Congenital heart defects research
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Advanced Software Engineering Methodologies
- MicroRNA in disease regulation
- Carbohydrate Chemistry and Synthesis
- Advanced Database Systems and Queries
- Chemical Synthesis and Analysis
- Distributed systems and fault tolerance
- Genetic and phenotypic traits in livestock
- Model-Driven Software Engineering Techniques
- Asymmetric Synthesis and Catalysis
- Computability, Logic, AI Algorithms
Agriculture Victoria
2024
Bates College
2016-2022
Central Maine Medical Center
2021
Judson University
2018-2019
Microsoft Research (United Kingdom)
2003-2018
Protein Technologies (United Kingdom)
2018
University of Alabama
2017
University of Virginia
2010-2016
University of Alabama at Birmingham
2014-2016
McCormick (United States)
2010-2016
Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, spatial associative learning memory. Despite deficits, Tcf4(+/−) enhanced long-term potentiation CA1 area hippocampus. In translationally oriented...
DNA methylation is known as the prima donna epigenetic mark for its critical role in regulating local gene transcription. Changes landscape of across genome occur during cellular transition, such differentiation and altered neuronal plasticity, become dysregulated disease states cancer. The TET family enzymes to be responsible catalyzing reverse process that demethylation by recognizing 5-methylcytosine oxidizing methyl group via an Fe(II)/alpha-ketoglutarate-dependent mechanism. Here, we...
Histone variants were recently discovered to regulate neural plasticity, with H2A.Z emerging as a memory suppressor. Using whole-genome sequencing of the mouse hippocampus, we show that basal occupancy is positively associated steady-state transcription, whereas learning-induced removal gene expression. AAV-mediated depletion enhanced fear and resulted in gene-specific alterations reinforcing role accumulated age, although it remained sensitive eviction. Learning-related occurred at largely...
MLJ compiles SML'97 into verifier-compliant Java byte-codes. Its features include type-checked interlanguage working extensions which allow ML and code to call each other, automatic recompilation management, compact compiled runtime performance which, using a 'just in time' compiling virtual machine, usually exceeds that of existing specialised bytecode interpreters for ML. Notable the compiler itself whole-program optimisation based on rewriting, compilation polymorphism by specialisation,...
Using a hippocampus-dependent contextual threat learning and memory task, we report widespread, coordinated DNA methylation changes in CA1 hippocampus of Sprague-Dawley rats specific to at genes involved synaptic transmission. Experience-dependent alternations gene expression were observed as early 1 h following acquisition became more pronounced after 24 h. Gene ontology analysis revealed significant enrichment functional categories related transmission that hypomethylated learning....
We present a series of CPS-based intermediate languages suitable for functional language compilation, arguing that they have practical benefits over direct-style based on A-normal form (ANF) or monads. Inlining functions demonstrates the most clearly: in ANF-based languages, inlining involves re-normalization step rearranges let expressions and possibly introduces new 'join point' function, monadic commuting conversions must be applied; contrast, our CPS is simple substitution variables variables.
Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers S1P, and thus, SphK inhibitors may prove effective in mitigation chemosensitization. Of two SphKs, SphK1 overexpression observed myriad cell lines tissues recognized presumptive target over poorly characterized SphK2. Herein, we present design synthesis amidine-based nanomolar subtype-selective inhibitors. A homology model...
The current study employed next-generation RNA sequencing to examine gene expression differences related brain aging, cognitive decline, and hippocampal subfields. Young aged rats were trained on a spatial episodic memory task. Hippocampal regions CA1, CA3, the dentate gyrus isolated. Poly-A mRNA was examined using two different platforms, Illumina, Ion Proton. Illumina platform used generate seed lists of genes that statistically differentially expressed across regions, ages, or in...
Whole-farm decision making is complex as many factors influence the profitability of pasture-based lamb production systems and other influences such skills attitudes also affect behaviours individual farmers. In this paper we used bioeconomic modelling to identify relative importance manipulating components in south-west Victoria quantified their likely impacts on whole-farm profitability. Four that varied relation genotype ewes time sale lambs were examined analysis. Two ‘systems’ based...
Sphingosine 1-phosphate (S1P), a potent phospholipid growth and trophic factor, is synthesized in vivo by two sphingosine kinases. Thus these kinases have been proposed as important drug targets for treatment of hyperproliferative diseases inflammation. We report here new class amidine-based analogues that are competitive inhibitors exhibiting varying degrees enzyme selectivity. These display K(I) values the submicromolar range both and, cultured vascular smooth muscle cells, decrease S1P...
A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this remain elusive. Tet1 oxidase has been shown to play a key role in active CNS. In study, we used gene knockout (Tet1KO) mice examine involvement consolidation storage adult brain. We found that ablation leads to: altered expression numerous genes, compensatory upregulation pathway various epigenetic modifiers. Moreover,...
We describe a Coq formalization of subset the x86 architecture. One emphasis model is brevity: using dependent types, type classes and notation we give semantics makeover that counters its reputation for baroqueness. bits, bytes, memory concretely functions can be computed inside itself; concrete representations are mapped across to mathematical objects in SSReflect library (naturals, integers modulo 2n) prove theorems. Finally, use support conventional assembly code syntax Coq, including...
Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder, classified as an autism spectrum disorder that caused by the haploinsufficiency of Transcription Factor 4 (TCF4). The most common non‐neurological symptoms in PTHS patients are gastrointestinal (GI) disturbances, mainly gastroesophageal reflux and severe constipation (in about 30 75% patients, respectively). We hypothesized recently recognized mouse model will exhibit problems with their gut function. conducted series vivo tests...
The dynamic regulation of DNA methylation in postmitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active demethylation. However, attempts pinpoint its exact role the nervous system have been hindered contradictory findings, perhaps due part, recent discovery that two isoforms Tet1 gene are differentially...
Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by monoallelic mutation or deletion in the transcription factor 4 ( TCF4 ) gene. Individuals with PTHS typically present first year of life developmental delay and exhibit intellectual disability, lack speech, motor incoordination. There are no effective treatments available for PTHS, but root cause disorder, haploinsufficiency, suggests that it could be treated normalizing gene expression. Here, we performed...
Type systems for programming languages with numeric types can be extended to support the checking of units measure. Quantification over then introduces a new kind parametric polymorphism corresponding Reynolds-style representation independence principle: that behaviour programs is invariant under changes used. We prove this 'dimensional invariance' result and describe four consequences. The first type an expression used derive equations which its properties respect scaling (akin Wadler's...
The tedium of writing pickling and unpickling functions by hand is relieved using a combinator library similar in spirit to the well-known parser combinators. Picklers for primitive types are combined support tupling, alternation, recursion, structure sharing. Code presented Haskell; an alternative implementation ML discussed.