20,335 research outputs found
Chaos in two black holes with next-to-leading order spin-spin interactions
We take into account the dynamics of a complete third post-Newtonian
conservative Hamiltonian of two spinning black holes, where the orbital part
arrives at the third post-Newtonian precision level and the spin-spin part with
the spin-orbit part includes the leading-order and next-to-leading-order
contributions. It is shown through numerical simulations that the
next-to-leading order spin-spin couplings play an important role in chaos. A
dynamical sensitivity to the variation of single parameter is also
investigated. In particular, there are a number of \textit{observable} orbits
whose initial radii are large enough and which become chaotic before
coalescence
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The functional impact of copy number variation in the human genome
Copy number variation (CNV) is a class of genetic variation where large segments of the genome vary in copy number among different individuals. It has become clear in the past decade that CNV affects a significant proportion of the human genome and can play an important role in human disease. With array-based copy number detection and the current generation of sequencing technologies, our ability to discover genetic variants is running far ahead of our ability to interpret their functional impact. One approach to close this gap is to explore statistical association between genetic variants and phenotypes. In contrast to the successes of genome-wide association studies for common disease using common single nucleotide polymorphism (SNP) as markers, the majority of disease CNVs discovered so far have low population frequencies and are mainly involved in rare developmental disorders. Another strategy to improve interpretation of genomic variants is to establish a predictive understanding of their functional impact. Large heterozygous deletions are of particular interest, since (i) loss-of-function (LOF) of coding sequences encompassed by large deletions can be relatively unambiguously ascribed and (ii) haploinsufficiency (HI), wherein only one functional copy of a gene is not sufficient to maintain normal phenotype, is a major cause of dominant diseases.
This thesis explored both approaches. Initially, I developed an informatics pipeline for robust discovery of CNVs from large numbers of samples genotyped using the Affymetrix whole-genome SNP array 6.0, to support both the association-based and prediction-based study. For the disease association strategy, I studied the role of both common and rare CNVs in severe early-onset obesity using a case-control design, from which a rare 220kb heterozygous deletion at 16p11.2 that encompasses SH2B1 was found causal for the phenotype and an 8kb common deletion upstream of NEGR1 was found to be significantly associated with the disease, particularly in females. Using the prediction-based approach, I characterized the properties of HI genes by comparing with genes observed to be deleted in apparently healthy individuals and I developed a prediction model to distinguish HI and haplosufficient (HS) genes using the most informative properties identified from these comparisons. An HI-based pathogenicity score was devised to distinguish pathogenic genic CNVs from benign genic CNVs. Finally, I proposed a probabilistic diagnostic framework to incorporate population variation, and integrate other sources of evidence, to enable an improved, and quantitative, identification of causal variants
Monitoring the Quality of After-school Services: Theoretical Logic, System Construction and Implementation Mechanisms
With the introduction of the “double reduction” policy in 2021, China’s after-school services have begun the historical process of germination, exploration, development and deepening. With the full coverage of after-school services, it is urgent to monitor the quality of after-school services, which is also in line with the requirements of the report of the 20th National Congress that “we should adhere to the people-centred development of education, accelerate the construction of high-quality education, accelerate the construction of a high-quality education system, develop quality education and promote educational equity”. Monitoring the quality of after-school services is a systematic, process-oriented and cyclical practice. The construction of a monitoring system should systematically integrate elements such as government, headmasters, teachers and parents, and should establish a collaborative mechanism of multiple subjects with clear responsibilities, an innovative mechanism of testing tools driven by big data, and a comprehensive mechanism for the long-term operation of the testing system
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