Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate ...chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98-99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.
Chiari malformations are regarded as a pathological continuum of hindbrain maldevelopments characterized by downward herniation of the cerebellar tonsils. The Chiari I malformation (CMI) is defined ...as tonsillar herniation of at least 3 to 5 mm below the foramen magnum. Increased detection of CMI has emphasized the need for more information regarding the clinical features of the disorder.
We examined a prospective cohort of 364 symptomatic patients. All patients underwent magnetic resonance imaging of the head and spine, and some were evaluated using CINE-magnetic resonance imaging and other neurodiagnostic tests. For 50 patients and 50 age- and gender-matched control subjects, the volume of the posterior cranial fossa was calculated by the Cavalieri method. The families of 21 patients participated in a study of familial aggregation.
There were 275 female and 89 male patients. The age of onset was 24.9+/-15.8 years (mean +/- standard deviation), and 89 patients (24%) cited trauma as the precipitating event. Common associated problems included syringomyelia (65%), scoliosis (42%), and basilar invagination (12%). Forty-three patients (12%) reported positive family histories of CMI or syringomyelia. Pedigrees for 21 families showed patterns consistent with autosomal dominant or recessive inheritance. The clinical syndrome of CMI was found to consist of the following: 1) headaches, 2) pseudotumor-like episodes, 3) a Meniere's disease-like syndrome, 4) lower cranial nerve signs, and 5) spinal cord disturbances in the absence of syringomyelia. The most consistent magnetic resonance imaging findings were obliteration of the retrocerebellar cerebrospinal fluid spaces (364 patients), tonsillar herniation of at least 5 mm (332 patients), and varying degrees of cranial base dysplasia. Volumetric calculations for the posterior cranial fossa revealed a significant reduction of total volume (mean, 13.4 ml) and a 40% reduction of cerebrospinal fluid volume (mean, 10.8 ml), with normal brain volume.
These data support accumulating evidence that CMI is a disorder of the para-axial mesoderm that is characterized by underdevelopment of the posterior cranial fossa and overcrowding of the normally developed hindbrain. Tonsillar herniation of less than 5 mm does not exclude the diagnosis. Clinical manifestations of CMI seem to be related to cerebrospinal fluid disturbances (which are responsible for headaches, pseudotumor-like episodes, endolymphatic hydrops, syringomyelia, and hydrocephalus) and direct compression of nervous tissue. The demonstration of familial aggregation suggests a genetic component of transmission.
Industry trends aimed at integrating higher levels of circuit functionality have triggered a proliferation of mixed analog-digital systems. Magnified noise coupling through the common chip substrate ...has made the design and verification of such systems an increasingly difficult task. In this paper we present a fast eigendecomposition technique that accelerates operator application in BEM methods and avoids the dense-matrix storage while taking all of the substrate boundary effects into account explicitly. This technique can be used for accurate and efficient modeling of substrate coupling effects in mixed-signal integrated circuits.
碩士
國立政治大學
經營管理碩士學程
90
Integration Marketing and Research & Development
Using New Product Development as Case Study
Advisor: Professor Lou, Yung Chien
Author: Yang, Hsi Chou (Mike)
EMBA Program- ...College of Commerce (NCCU)
Graduate Institute Technology and Innovation Management
ABSTRACT
Under the trend of globalization, product’s life cycle turns shorter with severe level of competition. Thereby, the development in new product and technology as well as product commercialization are more important than ever for enterprises today. Only the ones with the capability to efficiently integrate resources in dynamic market are able to harvest remarkable profits and strengthen market competitiveness. Especially under the dynamic changing environments, enterprises should utilize the global market needs and standard as its foundation to execute new product developments and organization structure.
This thesis is to study the key success factors of new product development under the integration between marketing and research
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1998.
Includes bibliographical references (leaves 131-135).
by Mike Chuan Chou.
Ph.D.
Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1994.
Includes bibliographical references (p. 67-69).
by Mike Chou.
M.S.
Accurately accounting for three-dimensional (3-D) geometry and distributed RC effects in on-chip interconnect is important for predicting crosstalk in memory cells, analog circuits, and regions of ...congested routing in digital circuits. In this paper we describe a multipole-accelerated, mixed surface-volume formulation, and a preconditioned model-order reduction algorithm for distributed RC, or electroquasistatic, simulation of 3-D integrated circuit interconnect. The difficulties arising from the ill conditioning inherent in the dynamic problem is effectively resolved by a combined surface-volume approach. Results are presented to demonstrate that the computational cost for extracting a complete reduced-order model is order N, where N is the number of surface unknowns. Finally, the multipole-accelerated code is used to investigate the accuracy of the one-dimensional diffusion equation for long RC lines.
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