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Twin Research and Human Genetics : the... Feb 2013This paper describes the Colorado Adoption Project (CAP), an ongoing genetically informative longitudinal study of behavioral development. We describe the features of...
This paper describes the Colorado Adoption Project (CAP), an ongoing genetically informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated-sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP's history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP's initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study's multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development.
Topics: Adolescent; Adoption; Adult; Child; Child, Preschool; Colorado; Diseases in Twins; Female; Gene-Environment Interaction; Genetics, Behavioral; Humans; Infant; Longitudinal Studies; Male; Parents; Prospective Studies; Registries; Siblings; Social Environment; Twins, Dizygotic; Twins, Monozygotic; Young Adult
PubMed: 23158098
DOI: 10.1017/thg.2012.109 -
Sensors (Basel, Switzerland) Nov 2016Due to the urgent need for high precision surgical equipment for minimally invasive spinal surgery, a novel robot-assistant system was developed for the accurate...
Due to the urgent need for high precision surgical equipment for minimally invasive spinal surgery, a novel robot-assistant system was developed for the accurate placement of pedicle screws in lumbar spinal surgeries. The structure of the robot was based on a macro-micro mechanism, which includes a serial mechanism (macro part) and a bi-planar 5R parallel mechanism (micro part). The macro part was used to achieve a large workspace, while the micro part was used to obtain high stiffness and accuracy. Based on the transfer function of dimension errors, the factors affecting the accuracy of the end effectors were analyzed. Then the manufacturing errors and joint angle error on the position-stance of the end effectors were investigated. Eventually, the mechanism of the strain energy produced by the deformation of linkage via forced assembly and displacements of the output point were calculated. The amount of the transfer errors was quantitatively analyzed by the simulation. Experimental tests show that the error of the bi-planar 5R mechanism can be controlled no more than 1 mm for translation and 1° for rotation, which satisfies the required absolute position accuracy of the robot.
PubMed: 27916869
DOI: 10.3390/s16122022 -
Genome Biology and Evolution Sep 2021Lysozyme enzymes provide classic examples of molecular adaptation and parallel evolution, however, nearly all insights to date come from chicken-type (c-type) lysozymes....
Lysozyme enzymes provide classic examples of molecular adaptation and parallel evolution, however, nearly all insights to date come from chicken-type (c-type) lysozymes. Goose-type (g-type) lysozymes occur in diverse vertebrates, with multiple independent duplications reported. Most mammals possess two g-type lysozyme genes (Lyg1 and Lyg2), the result of an early duplication, although some lineages are known to have subsequently lost one copy. Here we examine g-type lysozyme evolution across >250 mammals and reveal widespread losses of either Lyg1 or Lyg2 in several divergent taxa across the mammal tree of life. At the same time, we report strong evidence of extensive losses of both gene copies in cetaceans and sirenians, with an additional putative case of parallel loss in the tarsier. To validate these findings, we inspected published short-read data and confirmed the presence of loss of function mutations. Despite these losses, comparisons of selection pressures between intact g- and c-type lysozyme genes showed stronger purifying selection in the former, indicative of conserved function. Although the reasons for the evolutionary loss of g-type lysozymes in fully aquatic mammals are not known, we suggest that this is likely to at least partially relate to their hairlessness. Indeed, although Lyg1 does not show tissue-specific expression, recent studies have linked Lyg2 expression to anagen hair follicle development and hair loss. Such a role for g-type lysozyme would explain why the Lyg2 gene became obsolete when these taxa lost their body hair.
Topics: Animals; Cetacea; Evolution, Molecular; Mammals; Muramidase; Phylogeny
PubMed: 34450623
DOI: 10.1093/gbe/evab201 -
Nature Ecology & Evolution Feb 2021Parallelism, the evolution of similar traits in populations diversifying in similar conditions, provides strong evidence of adaptation by natural selection. Many studies...
Parallelism, the evolution of similar traits in populations diversifying in similar conditions, provides strong evidence of adaptation by natural selection. Many studies of parallelism focus on comparisons of different ecotypes or contrasting environments, defined a priori, which could upwardly bias the apparent prevalence of parallelism. Here, we estimated genomic parallelism associated with components of environmental and phenotypic variation at an intercontinental scale across four freshwater adaptive radiations (Alaska, British Columbia, Iceland and Scotland) of the three-spined stickleback (Gasterosteus aculeatus). We combined large-scale biological sampling and phenotyping with restriction site associated DNA sequencing (RAD-Seq) data from 73 freshwater lake populations and four marine ones (1,380 fish) to associate genome-wide allele frequencies with continuous distributions of environmental and phenotypic variation. Our three main findings demonstrate that (1) quantitative variation in phenotypes and environments can predict genomic parallelism; (2) genomic parallelism at the early stages of adaptive radiations, even at large geographic scales, is founded on standing variation; and (3) similar environments are a better predictor of genome-wide parallelism than similar phenotypes. Overall, this study validates the importance and predictive power of major phenotypic and environmental factors likely to influence the emergence of common patterns of genomic divergence, providing a clearer picture than analyses of dichotomous phenotypes and environments.
Topics: Animals; British Columbia; Genetics, Population; Genomics; Polymorphism, Single Nucleotide; Radiation; Scotland; Smegmamorpha
PubMed: 33257817
DOI: 10.1038/s41559-020-01341-8 -
PloS One 2019In neuroscience, computational modeling has become an important source of insight into brain states and dynamics. A basic requirement for computational modeling studies...
In neuroscience, computational modeling has become an important source of insight into brain states and dynamics. A basic requirement for computational modeling studies is the availability of efficient software for setting up models and performing numerical simulations. While many such tools exist for different families of neural models, there is a lack of tools allowing for both a generic model definition and efficiently parallelized simulations. In this work, we present PyRates, a Python framework that provides the means to build a large variety of rate-based neural models. PyRates provides intuitive access to and modification of all mathematical operators in a graph, thus allowing for a highly generic model definition. For computational efficiency and parallelization, the model is translated into a compute graph. Using the example of two different neural models belonging to the family of rate-based population models, we explain the mathematical formalism, software structure and user interfaces of PyRates. We show via numerical simulations that the behavior of the PyRates model implementations is consistent with the literature. Finally, we demonstrate the computational capacities and scalability of PyRates via a number of benchmark simulations of neural networks differing in size and connectivity.
Topics: Algorithms; Brain; Brain Mapping; Connectome; Electroencephalography; Humans; Magnetic Resonance Imaging; Models, Neurological; Models, Theoretical; Neurosciences
PubMed: 31841550
DOI: 10.1371/journal.pone.0225900 -
Proceedings. Biological Sciences Jul 2018The question of parallel evolution-what causes it, and how common it is-has long captured the interest of evolutionary biologists. Widespread urban development over the...
The question of parallel evolution-what causes it, and how common it is-has long captured the interest of evolutionary biologists. Widespread urban development over the last century has driven rapid evolutionary responses on contemporary time scales, presenting a unique opportunity to test the predictability and parallelism of evolutionary change. Here we examine urban evolution in an acorn-dwelling ant species, focusing on the urban heat island signal and the ant's tolerance of these altered urban temperature regimes. Using a common-garden experimental design with acorn ant colonies collected from urban and rural populations in three cities and reared under five temperature treatments in the laboratory, we assessed plastic and evolutionary shifts in the heat and cold tolerance of F1 offspring worker ants. In two of three cities, we found evolved losses of cold tolerance, and compression of thermal tolerance breadth. Results for heat tolerance were more complex: in one city, we found evidence of simple evolved shifts in heat tolerance in urban populations, though in another, the difference in urban and rural population heat tolerance depended on laboratory rearing temperature, and only became weakly apparent at the warmest rearing temperatures. The shifts in tolerance appeared to be adaptive, as our analysis of the fitness consequences of warming revealed that while urban populations produced more sexual reproductives under warmer laboratory rearing temperatures, rural populations produced fewer. Patterns of natural selection on thermal tolerances supported our findings of fitness trade-offs and local adaptation across urban and rural acorn ant populations, as selection on thermal tolerance acted in opposite directions between the warmest and coldest rearing temperatures. Our study provides mixed support for parallel evolution of thermal tolerance under urban temperature rise, and, importantly, suggests the promising use of cities to examine parallel and non-parallel evolution on contemporary time scales.
Topics: Adaptation, Biological; Animals; Ants; Biological Evolution; Cities; Cold Temperature; Hot Temperature; Reproduction; Thermotolerance
PubMed: 30051828
DOI: 10.1098/rspb.2018.0036 -
Micromachines Jun 2023Both the diversity and complexity of microfluidic systems have experienced a tremendous progress over the last decades, enabled by new materials, novel device concepts...
Both the diversity and complexity of microfluidic systems have experienced a tremendous progress over the last decades, enabled by new materials, novel device concepts and innovative fabrication routes. In particular the subfield of high-throughput screening, used for biochemical, genetic and pharmacological samples, has extensively emerged from developments in droplet microfluidics. More recently, new 3D device architectures enabled either by stacking layers of PDMS or by direct 3D-printing have gained enormous attention for applications in chemical synthesis or biomedical assays. While the first microfluidic devices were based on silicon and glass structures, those materials have not yet been significantly expanded towards 3D despite their high chemical compatibility, mechanical strength or mass-production potential. In our work, we present a generic fabrication route based on the implementation of vertical vias and a redistribution layer to create glass-silicon-glass 3D microfluidic structures. It is used to build different droplet-generating devices with several flow-focusing junctions in parallel, all fed from a single source. We study the effect of having several of these junctions in parallel by varying the flow conditions of both the continuous and the dispersed phases. We demonstrate that the generic concept enables an upscaling in the production rate by increasing the number of droplet generators per device without sacrificing the monodispersity of the droplets.
PubMed: 37512600
DOI: 10.3390/mi14071289 -
BioRxiv : the Preprint Server For... Mar 2023Material- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes...
Material- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature of implantation experiments. We introduce a 'plug and play' screening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelized screening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can "rescue" vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.
PubMed: 36993278
DOI: 10.1101/2023.03.16.533029 -
Micromachines Oct 2021Optical DNA mapping (ODM) has developed into an important technique for DNA analysis, where single DNA molecules are sequence-specifically labeled and stretched, for...
Optical DNA mapping (ODM) has developed into an important technique for DNA analysis, where single DNA molecules are sequence-specifically labeled and stretched, for example, in nanofluidic channels. We have developed an ODM assay to analyze bacterial plasmids-circular extrachromosomal DNA that often carry genes that make bacteria resistant to antibiotics. As for most techniques, the next important step is to increase throughput and automation. In this work, we designed and fabricated a nanofluidic device that, together with a simple automation routine, allows parallel analysis of up to 10 samples at the same time. Using plasmids encoding extended-spectrum beta-lactamases (ESBL), isolated from and , we demonstrate the multiplexing capabilities of the device when it comes to both many samples in parallel and different resistance genes. As a final example, we combined the device with a novel protocol for rapid cultivation and extraction of plasmids from fecal samples collected from patients. This combined protocol will make it possible to analyze many patient samples in one device already on the day the sample is collected, which is an important step forward for the ODM analysis of plasmids in clinical diagnostics.
PubMed: 34683285
DOI: 10.3390/mi12101234 -
Lifetime Data Analysis Apr 2022Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the...
Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the cause-specific etiology of breast and prostate cancers using the large-scale data from the Surveillance, Epidemiology, and End Results (SEER) Program, we encountered two major challenges that existing methods for estimating time-varying coefficients cannot tackle. First, these methods, dependent on expanding the original data in a repeated measurement format, result in formidable time and memory consumption as the sample size escalates to over one million. In this case, even a well-configured workstation cannot accommodate their implementations. Second, when the large-scale data under analysis include binary predictors with near-zero variance (e.g., only 0.6% of patients in our SEER prostate cancer data had tumors regional to the lymph nodes), existing methods suffer from numerical instability due to ill-conditioned second-order information. The estimation accuracy deteriorates further with multiple competing risks. To address these issues, we propose a proximal Newton algorithm with a shared-memory parallelization scheme and tests of significance and nonproportionality for the time-varying effects. A simulation study shows that our scalable approach reduces the time and memory costs by orders of magnitude and enjoys improved estimation accuracy compared with alternative approaches. Applications to the SEER cancer data demonstrate the real-world performance of the proximal Newton algorithm.
Topics: Algorithms; Humans; Male; Prostatic Neoplasms; SEER Program; Sample Size
PubMed: 35092553
DOI: 10.1007/s10985-021-09544-2