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Cartesian Genetic Programming for Memristive Logic Circuits [chapter]

Gerard David Howard, Larry Bull, Andrew Adamatzky
2012 Lecture Notes in Computer Science  
Usually the important parameters in the design and implementation of combinational logic circuits are the number of gates, transistors, and levels used in the design of a circuit. In this regard, various evolutionary paradigms with different competency have recently been introduced. However, while being advantageous, evolutionary paradigms also have some limitations including a) lack of confidence in reaching the correct answer, b) long convergence time, and c) restriction on the tests
more » ... with a higher number of input variables. In this work, we implement a genetic programming approach that given a Boolean function, outputs an equivalent circuit such that the truth table is covered, and the minimum number of gates (and to some extent, transistors and levels) are used. Furthermore, our implementation improves the aforementioned limitations by incorporating a self-repairing feature (improving limitation a); efficient use of the conceivable coding space of the problem, which virtually brings about a kind of parallelism and improves the convergence time (improving limitation b). Moreover, we apply our method to solve the Boolean functions with a higher number of inputs (improving limitation c). These issues are verified through multiple tests, and the results obtained are reported.
doi:10.1007/978-3-642-29139-5_4 fatcat:mukreo3sbvb4fezmymbjpmfmx4

On Self-Adaptive Mutation Restarts for Evolutionary Robotics with Real Rotorcraft [article]

Gerard David Howard
2017 arXiv   pre-print
Self-adaptive parameters are increasingly used in the field of Evolutionary Robotics, as they allow key evolutionary rates to vary autonomously in a context-sensitive manner throughout the optimisation process. A significant limitation to self-adaptive mutation is that rates can be set unfavourably, which hinders convergence. Rate restarts are typically employed to remedy this, but thus far have only been applied in Evolutionary Robotics for mutation-only algorithms. This paper focuses on the
more » ... vel at which evolutionary rate restarts are applied in population-based algorithms with more than 1 evolutionary operator. After testing on a real hexacopter hovering task, we conclude that individual-level restarting results in higher fitness solutions without fitness stagnation, and population restarts provide a more stable rate evolution. Without restarts, experiments can become stuck in suboptimal controller/rate combinations which can be difficult to escape from.
arXiv:1703.10754v2 fatcat:j7dynow6nbglfbtezac2mzpcme

Interventional Fellowship in Structural and Congenital Heart Disease for Adults

Carlos E. Ruiz, Ted E. Feldman, Ziyad M. Hijazi, David R. Holmes, John G. Webb, E. Murat Tuzcu, Howard Herrmann, Gerard R. Martin
2010 JACC: Cardiovascular Interventions  
and Washington, DC Training for structural and adult congenital heart disease interventions remains undeveloped. With the advent of recent percutaneous interventions for the treatment of structural and valvular heart disease, such as transcatheter aortic and pulmonary valve implantation, mitral valve repair, and the expansion of shunt closure procedures, there is a clear need to define the training requirements for this category of procedures. The training needs to be aligned with the goals and
more » ... priorities of a basic or advanced level and be categorized into acquired and congenital. This document will define the training needs and knowledge base for the developing field of structural heart disease intervention. (J Am Coll Cardiol Intv 2010;3:e1-15)
doi:10.1016/j.jcin.2010.08.010 pmid:20850086 fatcat:s6ohjwqflbeabkugo7tdk75ej4

Stretch-regulated Exocytosis/Endocytosis in Bladder Umbrella Cells

Steven T. Truschel, Edward Wang, Wily G. Ruiz, Som-Ming Leung, Raul Rojas, John Lavelle, Mark Zeidel, David Stoffer, Gerard Apodaca, Howard Riezman
2002 Molecular Biology of the Cell  
The epithelium of the urinary bladder must maintain a highly impermeable barrier despite large variations in urine volume during bladder filling and voiding. To study how the epithelium accommodates these volume changes, we mounted bladder tissue in modified Ussing chambers and subjected the tissue to mechanical stretch. Stretching the tissue for 5 h resulted in a 50% increase in lumenal surface area (from ϳ2900 to 4300 m 2 ), exocytosis of a population of discoidal vesicles located in the
more » ... l cytoplasm of the superficial umbrella cells, and release of secretory proteins. Surprisingly, stretch also induced endocytosis of apical membrane and 100% of biotinlabeled membrane was internalized within 5 min after stretch. The endocytosed membrane was delivered to lysosomes and degraded by a leupeptin-sensitive pathway. Last, we show that the exocytic events were mediated, in part, by a cyclic adenosine monophosphate, protein kinase A-dependent process. Our results indicate that stretch modulates mucosal surface area by coordinating both exocytosis and endocytosis at the apical membrane of umbrella cells and provide insight into the mechanism of how mechanical forces regulate membrane traffic in nonexcitable cells. Article published online ahead of print. Mol. Biol. Cell 10.1091/ mbc.01-09 -0435. Article and publication date are at www.molbiolcell.org/cgi/
doi:10.1091/mbc.01-09-0435 pmid:11907265 pmcid:PMC99602 fatcat:zgujbngiabhldg5dyiyfs2qbri

On the effects of node duplication and connection-oriented constructivism in neural XCSF

Gerard David Howard, Larry Bull
2008 Proceedings of the 2008 GECCO conference companion on Genetic and evolutionary computation - GECCO '08  
For artificial entities to achieve high degrees of autonomy they will need to display appropriate adaptability. In this sense adaptability includes representational flexibility guided by the environment at any given time. This paper presents the use of constructivism-inspired mechanisms within a neural learning classifier system which exploits parameter self-adaptation as an approach to realize such behavior. Various network growth/regression mechanisms are implemented and their performances
more » ... pared. The system uses a rule structure in which each is represented by an artificial neural network. It is shown that appropriate internal rule complexity emerges during learning at a rate controlled by the system.
doi:10.1145/1388969.1389010 dblp:conf/gecco/HowardB08 fatcat:2uhdczusnbcjridambe7fcmgqi

Interventional fellowship in structural and congenital heart disease for adults

Carlos E. Ruiz, Ted E. Feldman, Ziyad M. Hijazi, David R. Holmes, John G. Webb, E. Murat Tuzcu, Howard Herrmann, Gerard R. Martin
2010 Catheterization and cardiovascular interventions  
Training for structural and adult congenital heart disease interventions remains undeveloped. With the advent of recent percutaneous interventions for the treatment of structural and valvular heart disease, such as transcatheter aortic and pulmonary valve implantation, mitral valve repair, and the expansion of shunt closure procedures, there is a clear need to define the training requirements for this category of procedures. The training needs to be aligned with the goals and priorities of a
more » ... ic or advanced level and be categorized into acquired and congenital. This document will define the training needs and knowledge base for the developing field of structural heart disease intervention. V C 2010 Wiley-Liss, Inc.
doi:10.1002/ccd.22702 pmid:20602482 fatcat:6cebvrz2ubf6nd75priqxnjy74

ORGANIC MEMRISTOR DEVICES FOR LOGIC ELEMENTS WITH MEMORY

VICTOR EROKHIN, GERARD DAVID HOWARD, ANDREW ADAMATZKY
2012 International Journal of Bifurcation and Chaos in Applied Sciences and Engineering  
However, the realization of logic elements based on memristors has also been reported , Xia et al.(2009)] , including automated search of potential circuit topologies [Howard et al.(2012) ].  ... 
doi:10.1142/s0218127412502835 fatcat:4kufxcj5fnfo3fknah4pz4qd74

Personalized genetic assessment of age associated Alzheimers disease risk [article]

Rahul S. Desikan, Chun Chieh Fan, Yunpeng Wang, Andrew J. Schork, Howard J. Cabral, Adrienne Cupples, Wesley K. Thompson, Lilah Besser, Walter A. Kukull, Dominic Holland, Chi-Hua Chen, James B. Brewer (+22 others)
2016 bioRxiv   pre-print
Importance: Identifying individuals at risk for developing Alzheimers disease (AD) is of utmost importance. Although genetic studies have identified APOE and other AD associated single nucleotide polymorphisms (SNPs), genetic information has not been integrated into an epidemiological framework for personalized risk prediction. Objective: To develop, replicate and validate a novel polygenic hazard score for predicting age-specific risk for AD. Setting: Multi-center, multi-cohort genetic and
more » ... ical data. Participants: We assessed genetic data from 17,008 AD patients and 37,154 controls from the International Genetics of Alzheimers Project (IGAP), and 6,409 AD patients and 9,386 older controls from Phase 1 Alzheimers Disease Genetics Consortium (ADGC). As independent replication and validation cohorts, we also evaluated genetic, neuroimaging, neuropathologic, CSF and clinical data from ADGC Phase 2, National Institute of Aging Alzheimers Disease Center (NIA ADC) and Alzheimers Disease Neuroimaging Initiative (ADNI) (total n = 20,680) Main Outcome(s) and Measure(s): Use the IGAP cohort to first identify AD associated SNPs (at p < 10-5). Next, integrate these AD associated SNPs into a Cox proportional hazards model using ADGC phase 1 genetic data, providing a polygenic hazard score (PHS) for each participant. Combine population based incidence rates, and genotype-derived PHS for each individual to derive estimates of instantaneous risk for developing AD, based on genotype and age. Finally, assess replication and validation of PHS in independent cohorts. Results: Individuals in the highest PHS quantiles developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE 3/3 individuals, PHS modified expected age of AD onset by more than 10 years between the lowest and highest deciles. In independent cohorts, PHS strongly predicted empirical age of AD onset (p = 1.1 x 10-26), longitudinal progression from normal aging to AD (p = 1.54 x 10-10) and associated with markers of AD neurodegeneration. Conclusions: We developed, replicated and validated a clinically usable PHS for quantifying individual differences in age-specific risk of AD. Beyond APOE, polygenic architecture plays an important role in modifying AD risk. Precise quantification of AD genetic risk will be useful for early diagnosis and therapeutic strategies.
doi:10.1101/074864 fatcat:ig2cwzkq25gdroh7p7k3clg6ia

Examining New Preoperative Assessment Tools

Alok Kapoor, Nicholas S. Shaffer, Christine M. McDonough, Daniel K. White, Na Wang, Pamela Rosenkranz, Andrew Glantz, David McAneny, Gerard M. Doherty, Howard J. Cabral, Jerry H. Gurwitz, Roger A. Fielding (+2 others)
2016 Journal of The American Geriatrics Society  
doi:10.1111/jgs.14349 pmid:27590632 pmcid:PMC5319588 fatcat:vt5pplj7r5bujgd6dl6s45usua

Fibronectin Fragments and the Cleaving Enzyme ADAM-8 in the Degenerative Human Intervertebral Disc

Nancy Ruel, Dessislava Z. Markova, Sherrill L. Adams, Carla Scanzello, Gabriella Cs-Szabo, David Gerard, Peng Shi, D. Greg Anderson, Marc Zack, Howard S. An, Di Chen, Yejia Zhang
2014 Spine  
Study Design-The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective-To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data- The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the
more » ... n of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods-Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA 271 . A purified 29 kDa FN-f was used to allow estimation of the
doi:10.1097/brs.0000000000000397 pmid:25010013 pmcid:PMC4229950 fatcat:3ifh76vgqncwjflw4x3ne4h5gq

Exploring concordance and discordance for return of incidental findings from clinical sequencing

Robert C. Green, Jonathan S. Berg, Gerard T. Berry, Leslie G. Biesecker, David P. Dimmock, James P. Evans, Wayne W. Grody, Madhuri R. Hegde, Sarah Kalia, Bruce R. Korf, Ian Krantz, Amy L. McGuire (+6 others)
2012 Genetics in Medicine  
Special article Purpose: The aim of this study was to explore specific conditions and types of genetic variants that specialists in genetics recommend should be returned as incidental findings in clinical sequencing. methods: Sixteen specialists in clinical genetics and/or molecular medicine selected variants in 99 common conditions to return to the ordering physician if discovered incidentally through whole-genome sequencing. For most conditions, the specialists independently considered three
more » ... olecular scenarios for both adults and minor children: a known pathogenic mutation, a truncating variant presumed pathogenic (where other truncating variants are known to be pathogenic), and a missense variant predicted in silico to be pathogenic. Results: On average, for adults and children, respectively, each specialist selected 83.5 and 79.0 conditions or genes of 99 in the known pathogenic mutation categories, 57.0 and 53.5 of 72 in the truncating variant categories, and 33.4 and 29.7 of 72 in the missense variant categories. Concordance in favor of disclosure within the adult/ known pathogenic mutation category was 100% for 21 conditions or genes and 80% or higher for 64 conditions or genes. conclusion: Specialists were highly concordant for the return of findings for 64 conditions or genes if discovered incidentally during whole-exome sequencing or whole-genome sequencing. Genet Med 2012:14(4):405-410
doi:10.1038/gim.2012.21 pmid:22422049 pmcid:PMC3763716 fatcat:juropz5dnfdlthux3hduisw5uu

Lipid associated polygenic enrichment in Alzheimer's disease [article]

Iris Broce, Chin Hong Tan, Chun Chieh Fan, Aree Witoelar, Natalie Wen, Iris Jansen, Christopher Hess, William Dillon, Christine Glastonbury, Maria Glymour, Jennifer Yokoyama, Fanny Elahi (+17 others)
2018 bioRxiv   pre-print
Cardiovascular (CV) and lifestyle associated risk factors (RFs) are increasingly recognized as important for Alzheimer's disease (AD) pathogenesis. Beyond the ε4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV associated genes also increase risk for AD (genetic pleiotropy). Using large genome-wide association studies (GWASs) (total n > 500,000 cases and controls) and validated tools to quantify genetic pleiotropy, we systematically identified single nucleotide
more » ... olymorphisms (SNPs) jointly associated with AD and one or more CV RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist hip ratio (WHR), total cholesterol (TC), low-density (LDL) and high-density lipoprotein (HDL). In fold enrichment plots, we observed robust genetic enrichment in AD as a function of plasma lipids (TC, LDL, and HDL); we found minimal AD genetic enrichment conditional on BMI, T2D, CAD, and WHR. Beyond APOE, at conjunction FDR < 0.05 we identified 57 SNPs on 19 different chromosomes that were jointly associated with AD and CV outcomes including APOA4, ABCA1, ABCG5, LIPG, and MTCH2/SPI1. We found that common genetic variants influencing AD are associated with multiple CV RFs, at times with a different directionality of effect. Expression of these AD/CV pleiotropic genes was enriched for lipid metabolism processes, over-represented within astrocytes and vascular structures, highly co-expressed, and differentially altered within AD brains. Beyond APOE, we show that the polygenic component of AD is enriched for lipid associated RFs. Rather than a single causal link between genetic loci, RF and the outcome, we found that common genetic variants influencing AD are associated with multiple CV RFs. Our collective findings suggest that a network of genes involved in lipid biology also influence Alzheimer's risk.
doi:10.1101/383844 fatcat:g4sf3v7kyzcj3fmqdbp6wg5jcu

A platform for discovery: The University of Pennsylvania Integrated Neurodegenerative Disease Biobank

Jon B. Toledo, Vivianna M. Van Deerlin, Edward B. Lee, EunRan Suh, Young Baek, John L. Robinson, Sharon X. Xie, Jennifer McBride, Elisabeth M. Wood, Theresa Schuck, David J. Irwin, Rachel G. Gross (+12 others)
2014 Alzheimer's & Dementia  
Neurodegenerative diseases (NDs) are defined by the accumulation of abnormal protein deposits in the central nervous system (CNS), and only neuropathological examination enables a definitive diagnosis. Brain banks and their associated scientific programs have shaped the actual knowledge of NDs, identifying and characterizing the CNS deposits that define new diseases, formulating staging schemes, and establishing correlations between neuropathological changes and clinical features. However,
more » ... banks have evolved to accommodate the banking of biofluids as well as DNA and RNA samples. Moreover, the value of biobanks is greatly enhanced if they link all the multidimensional clinical and laboratory information of each case, which is accomplished, optimally, using systematic and standardized operating procedures, and in the framework of multidisciplinary teams with the support of a flexible and user-friendly database system that facilitates the sharing of information of all the teams in the network. We describe a biobanking system that is a platform for discovery research at
doi:10.1016/j.jalz.2013.06.003 pmid:23978324 pmcid:PMC3933464 fatcat:twfsxkfnprgefnn75ukjsu3vru

β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity

Hui Zheng, Minghao Jiang, Myrna E. Trumbauer, Dalip J.S. Sirinathsinghji, Ruth Hopkins, David W. Smith, Robert P. Heavens, Gerard R. Dawson, Susan Boyce, Michael W. Conner, Karla A. Stevens, Hilda H. Slunt (+3 others)
1995 Cell  
doi:10.1016/0092-8674(95)90073-x pmid:7758106 fatcat:cqmyxwhj2zb7jd6v7e2vwvtbpm

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score

Rahul S. Desikan, Chun Chieh Fan, Yunpeng Wang, Andrew J. Schork, Howard J. Cabral, L. Adrienne Cupples, Wesley K. Thompson, Lilah Besser, Walter A. Kukull, Dominic Holland, Chi-Hua Chen, James B. Brewer (+23 others)
2017 PLoS Medicine  
Genetic variants can be integrated within an epidemiology framework to derive a polygenic score that can quantify individual differences in age-specific genetic risk for AD, beyond APOE. • Quantification of inherited genetic variation may prove useful for AD risk stratification and for therapeutic trials. Polygenic hazard score for Alzheimer disease PLOS Medicine | Fig 2. Kaplan-Meier estimates and Cox proportional hazard model fits among APOE ε3/3 individuals in the ADGC Phase 1 dataset,
more » ... ing NIA ADC and ADNI samples. The solid lines represent the Cox fit, whereas the dashed lines and shaded regions represent the Kaplan-Meier estimations with 95% confidence intervals.
doi:10.1371/journal.pmed.1002258 pmid:28323831 pmcid:PMC5360219 fatcat:wjq6syjohnf75mipp32gca3dgy
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