Endurance exercise capacity is a powerful predictor of health status. Having low levels of endurance exercise capacity has been linked with cardiovascular disease. Variation in endurance exercise ...capacity, measured during a graded exercise test, has been reported across cross-section, twin, and family studies. This variation is evidence of a genetic component to the phenotype of endurance exercise capacity: however, the genetic factors responsible for explaining this variation are undefined, in part because previous research has been performed on a limited scale. Therefore, three sets of experiments were designed to identify: 1) Novel quantitative trait loci (QTL) for endurance exercise capacity in 34 strains of inbred mice using genome-wide association mapping. 2) The effect of chromosome substitution on endurance exercise capacity using linkage analysis in F2 mice. 3) The effect of chromosome substitution on endurance exercise capacity using wild-derived mice. The main findings of this dissertation are: 1) There are strain-specific differences in endurance exercise capacity across 34 strains of male inbred mice. Genome-wide association mapping identified novel putative QTL on chromosomes 2, 7, 11, and 13. 2) Linkage analysis identified a novel QTL on chromosome 14 at the 56 cM position for run time and work. Linkage analysis also identified a potential sex-specific QTL, with the identified QTL significant for male mice only. 3) Novel putative QTL were identified on chromosomes 3 and 14 in chromosome substitution mice from wild-derived mice. These data suggest that chromosome 14 is an important contributor to the genetic regulation of intrinsic endurance exercise capacity. These studies support a genetic component to endurance exercise capacity by identifying strain-specific differences and novel, putative QTL.
Considers features of a postmodern classroom conceived as a complex, socially distributed cognitive system that exemplifies distributed cognition. Presents a case study based on a documentary film, ..."The Dig", that describes a middle school class's archaeological dig that shows instructional innovations that liberate the learning process. (Author/LRW)
Resistance to flavivirus-induced disease is conferred by a single gene that encodes oligoadenylate synthetase (Oas) 1b (Oas1b). Oas1b is not a functional synthetase suggesting its anti-flavivirus ...mechanism is RNase L-independent and that it may be mediated by interactions with other host cell protein(s). A yeast two-hybrid screen was used to identify host cell binding partners of Oas1b. Candidate partners were confirmed by yeast co-transformation and co-immunoprecipitation analyses. Oxysterol binding protein-related 1L (ORP1L) and ATP binding cassette subfamily F 3 (ABCF3) were found to interact with Oas1b. RNAi knockdown studies suggested that ORP1L and ABCF3 form a tripartite complex with Oas1b that is critical for the flavivirus-induced disease resistance mechanism. Stresses including oxidation, nutrient starvation, and viral infections often induce the formation of stress granules (SGs) in eukaryotic cells. In response to stress, eIF2α kinases phosphorylate eIF2α leading to stalled 48S pre-initiation complexes and SG formation. West Nile virus (WNV) Eg101 infections were previously shown not to induce the formation of SGs. Infections with viruses of other natural WNV strains, as well as a WNV lineage 1/2-based infectious clone (W956IC) were analyzed and only W956IC infections were found to induce SGs. eIF2α kinase knockout MEFs were used to show that the W956IC-induced SGs were PKR-dependent. WNV chimeras were made by inserting Eg101 genes into the W956IC backbone. Chimeras replacing NS5 or NS1 and NS5 or NS1 and NS3 and NS4a reduced SG formation as well as early viral RNA synthesis similar to Eg101 infections. W956IC infections but not Eg101 infections were shown to produce exposed viral dsRNA at early times after infection. The data suggest that natural WNV infections evade the cell SG response by suppressing the amplification of viral RNA until cytoplasmic membranes have been remodeled to protect replication complexes from detection. It was previously reported that WNV Eg101 infections inhibited the formation of arsenite-induced SGs. The ability of other natural WNV strain infections to inhibit SG formation by arsenite (HRI), DTT (PERK), W956IC co-infection (PKR), and heat shock treatments was assessed. WNV infections only inhibited arsenite-induced SG formation suggesting that WNV infections specifically suppress the response to oxidative intermediates.
Accurate and scalable methods for computational quantum chemistry can accelerate research and development in many fields, ranging from drug discovery to advanced material design. Solving the ...electronic Schrodinger equation is the core problem of computational chemistry. However, the combinatorial complexity of this problem makes it intractable to find exact solutions, except for very small systems. The idea of quantum computing originated from this computational challenge in simulating quantum-mechanics. We propose an end-to-end quantum chemistry pipeline based on the variational quantum eigensolver (VQE) algorithm and integrated with both HPC-based simulators and a trapped-ion quantum computer. Our platform orchestrates hundreds of simulation jobs on compute resources to efficiently complete a set of ab initio chemistry experiments with a wide range of parameterization. Per- and poly-fluoroalkyl substances (PFAS) are a large family of human-made chemicals that pose a major environmental and health issue globally. Our simulations includes breaking a Carbon-Fluorine bond in trifluoroacetic acid (TFA), a common PFAS chemical. This is a common pathway towards destruction and removal of PFAS. Molecules are modeled on both a quantum simulator and a trapped-ion quantum computer, specifically IonQ Aria. Using basic error mitigation techniques, the 11-qubit TFA model (56 entangling gates) on IonQ Aria yields near-quantitative results with milli-Hartree accuracy. Our novel results show the current state and future projections for quantum computing in solving the electronic structure problem, push the boundaries for the VQE algorithm and quantum computers, and facilitates development of quantum chemistry workflows.
Attachment between an infant and his or her parents is a major topic within developmental psychology. An increasing number of psychologists, evolutionary biologists and anthropologists are ...articulating their doubts that attachment theory in its present form is applicable worldwide, without, however, denying that the development of attachment is a universal need. This book brings together leading scholars from psychology, anthropology and related fields to reformulate attachment theory in order to fit the cultural realities of our world. Contributions are based on empirical research and observation in a variety of cultural contexts. They are complemented by careful evaluation and deconstruction of many of the underlying premises and assumptions of attachment theory and of conventional research on the role of infant-parent attachment in human development. The book creates a contextual cultural understanding of attachment that will provide the basis for a groundbreaking reconceptualization of attachment theory.
In the first phase of nation-state development, adult education serves in the creation of nationalism and consensus. As the nation enters the world stage, adult education enforces national and ...cultural identity and meets professionalizing needs. As consensus loosens and pluralism emerges, adult education may become a symbol of conflict between competing needs and interests of special groups. (SK)
Endurance exercise capacity is a powerful predictor of health status. Having low levels of endurance exercise capacity has been linked with cardiovascular disease. Variation in endurance exercise ...capacity, measured during a graded exercise test, has been reported across cross-section, twin, and family studies. This variation is evidence of a genetic component to the phenotype of endurance exercise capacity: however, the genetic factors responsible for explaining this variation are undefined, in part because previous research has been performed on a limited scale. Therefore, three sets of experiments were designed to identify: 1) Novel quantitative trait loci (QTL) for endurance exercise capacity in 34 strains of inbred mice using genome-wide association mapping. 2) The effect of chromosome substitution on endurance exercise capacity using linkage analysis in F2 mice. 3) The effect of chromosome substitution on endurance exercise capacity using wild-derived mice.
The main findings of this dissertation are: 1) There are strain-specific differences in endurance exercise capacity across 34 strains of male inbred mice. Genome-wide association mapping identified novel putative QTL on chromosomes 2, 7, 11, and 13. 2) Linkage analysis identified a novel QTL on chromosome 14 at the 56 cM position for run time and work. Linkage analysis also identified a potential sex-specific QTL, with the identified QTL significant for male mice only. 3) Novel putative QTL were identified on chromosomes 3 and 14 in chromosome substitution mice from wild-derived mice. These data suggest that chromosome 14 is an important contributor to the genetic regulation of intrinsic endurance exercise capacity. These studies support a genetic component to endurance exercise capacity by identifying strain-specific differences and novel, putative QTL.
Resistance to flavivirus-induced disease is conferred by a single gene that encodes oligoadenylate synthetase (Oas) 1b (Oas1b). Oas1b is not a functional synthetase suggesting its anti-flavivirus ...mechanism is RNase L-independent and that it may be mediated by interactions with other host cell protein(s). A yeast two-hybrid screen was used to identify host cell binding partners of Oas1b. Candidate partners were confirmed by yeast co-transformation and co-immunoprecipitation analyses. Oxysterol binding protein-related 1L (ORP1L) and ATP binding cassette subfamily F 3 (ABCF3) were found to interact with Oas1b. RNAi knockdown studies suggested that ORP1L and ABCF3 form a tripartite complex with Oas1b that is critical for the flavivirus-induced disease resistance mechanism.
Stresses including oxidation, nutrient starvation, and viral infections often induce the formation of stress granules (SGs) in eukaryotic cells. In response to stress, eIF2α kinases phosphorylate eIF2α leading to stalled 48S pre-initiation complexes and SG formation. West Nile virus (WNV) Eg101 infections were previously shown not to induce the formation of SGs. Infections with viruses of other natural WNV strains, as well as a WNV lineage 1/2-based infectious clone (W956IC) were analyzed and only W956IC infections were found to induce SGs. eIF2α kinase knockout MEFs were used to show that the W956IC-induced SGs were PKR-dependent. WNV chimeras were made by inserting Eg101 genes into the W956IC backbone. Chimeras replacing NS5 or NS1 and NS5 or NS1 and NS3 and NS4a reduced SG formation as well as early viral RNA synthesis similar to Eg101 infections. W956IC infections but not Eg101 infections were shown to produce exposed viral dsRNA at early times after infection. The data suggest that natural WNV infections evade the cell SG response by suppressing the amplification of viral RNA until cytoplasmic membranes have been remodeled to protect replication complexes from detection.
It was previously reported that WNV Eg101 infections inhibited the formation of arsenite-induced SGs. The ability of other natural WNV strain infections to inhibit SG formation by arsenite (HRI), DTT (PERK), W956IC co-infection (PKR), and heat shock treatments was assessed. WNV infections only inhibited arsenite-induced SG formation suggesting that WNV infections specifically suppress the response to oxidative intermediates.
PDF
