School bus selection, routing and scheduling.

The aim of this thesis is to develop formulations and exact algorithms for the school bus routing and scheduling problem and to develop an integrated software implementation using Xpress-MP/CPLEX and ArcGIS of ESRI, a geographical information system software package. In this thesis, bus flow, single commodity flow, two-commodity flow, multi-commodity flow, and time window formulations have been developed. They capture all of the important elements of the School Bus Routing and Scheduling Problem (SBRSP) including homogeneous or heterogeneous bus fleets, the identification of bus stops from a large set of potential bus stops, and the assignment of students to stops and stops to routes. They allow for the one stop-one bus and one stop-multi bus scenarios. Each formulation of the SBRSP has a linear programming relaxation and we present the relationships among them. We present a Branch-and-Cut exact algorithm which makes use of new linearization techniques, new valid inequalities, and the first valid equalities. We develop an integrated software package that is based on Geographical Information System (GIS) map-based interface, linking to an Xpress-MP/CPLEX solver. The interface between GIS and Xpress-MP is written in VBA and VC++.Dept. of Mathematics and Statistics. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2005 .K4. Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 6250. Thesis (Ph.D.)--University of Windsor (Canada), 2005

Establishment of linkage phase, using Oxford Nanopore Technologies, for preimplantation genetic testing of Coffin-Lowry syndrome with a de novo RPS6KA3 mutation

Background: This study aimed to perform preimplantation genetic testing (PGT) for a female Coffin-Lowry Syndrome (CLS) patient with a de novo mutation (DNM) in RPS6KA3. It was challenging to establish the haplotype in this family because of the lack of information from affected family members. Hence, we explored a new and reliable strategy for the detection of the DNM in PGT, using Oxford Nanopore Technologies (ONT) and the MARSALA platform.Methods: We performed whole-exome sequencing (WES) on the proband and confirmed the pathogenic mutation by Sanger sequencing. The proband then underwent PGT to prevent the transmission of the pathogenic mutation to her offspring. We diverged from the conventional methods and used long-read sequencing (LRS) on the ONT platform to directly detect the mutation and nearby SNPs, for construction of the haplotype in the preclinical phase of PGT. In the clinical phase of embryo diagnosis, the MARSALA method was used to detect both the SNP-based haplotype and chromosome copy number variations (CNVs), in each blastocyst. Finally, a normal embryo was selected by comparison to the haplotype of the proband and transferred into the uterus. Sanger sequencing and karyotyping were performed by amniocentesis, at 17 weeks of gestation, to confirm the accuracy of PGT.Results: Using WES, we found the novel, heterozygous, pathogenic c.1496delG (p.Gly499Valfs*25) mutation of RPS6KA3 in the proband. The SNP-based haplotype that was linked to the pathogenic mutation site was successfully established in the proband, without the need for other family members to be tested with ONT. Eight blastocysts were biopsied to perform PGT and were assessed with a haplotype linkage analysis (30 SNP sites selected), to give results that were consistent with direct mutation detection using Sanger sequencing. The results of PGT showed that three of the eight blastocysts were normal, without the DNM. Moreover, the patient had a successful pregnancy, after transfer of a normal blastocyst into the uterus, and delivered a healthy baby.Conclusion: The ONT platform, combined with the MARSALA method, can be used to perform PGT for DNM patients without the need for other samples as a reference

Early on‐demand drainage or standard management for acute pancreatitis patients with acute necrotic collections and persistent organ failure: a pilot randomized controlled trial

Background/Purpose The current standard care for acute pancreatitis with acute necrotic collections (ANC) is to postpone invasive intervention for four weeks when indicated. However, in patients with persistent organ failure (POF), this delayed approach may prolong organ failure. In this study, we aimed to assess the feasibility and safety of earlier drainage for acute pancreatitis patients with ANC and POF. Methods A single‐center, randomized controlled trial was conducted. Eligible patients were randomly assigned to either the early on‐demand (EOD) group or the standard management(SM) group. Within 21 days of randomization, early drainage was triggered by unremitted or worsening organ failure in the EOD group. The primary endpoint was a composite of major complications/death during 90‐days follow‐up. Results 30 patients were randomized. Within 21 days of randomization, 8/15 patients (53%) in the EOD group underwent percutaneous drainage, while 4/15 patients (27%) in the SM group did so (P=0.26). The primary outcome occurred in 3/15 (20%) patients in the EOD group and 7/15(46.7%) in the controls (p=0.25, relative risk 0.43, 95%CI 0.14 to1.35)

Regulatory network of secondary metabolism in Brassica rapa:insight into the glucosinolate pathway

Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical genomics approach to identify regulatory genes for six biosynthetic pathways of health-related phytochemicals, i.e carotenoids, tocopherols, folates, glucosinolates, flavonoids and phenylpropanoids. Leaves from six weeks-old plants of a Brassica rapa doubled haploid population, consisting of 92 genotypes, were profiled for their secondary metabolite composition, using both targeted and LC-MS-based untargeted metabolomics approaches. Furthermore, the same population was profiled for transcript variation using a microarray containing EST sequences mainly derived from three Brassica species: B. napus, B. rapa and B. oleracea. The biochemical pathway analysis was based on the network analyses of both metabolite QTLs (mQTLs) and transcript QTLs (eQTLs). Co-localization of mQTLs and eQTLs lead to the identification of candidate regulatory genes involved in the biosynthesis of carotenoids, tocopherols and glucosinolates. We subsequently focused on the well-characterized glucosinolate pathway and revealed two hotspots of co-localization of eQTLs with mQTLs in linkage groups A03 and A09. Our results indicate that such a large-scale genetical genomics approach combining transcriptomics and metabolomics data can provide new insights into the genetic regulation of metabolite composition of Brassica vegetables

Biased Gene Fractionation and Dominant Gene Expression among the Subgenomes of Brassica rapa

Polyploidization, both ancient and recent, is frequent among plants. A “two-step theory" was proposed to explain the meso-triplication of the Brassica “A" genome: Brassica rapa. By accurately partitioning of this genome, we observed that genes in the less fractioned subgenome (LF) were dominantly expressed over the genes in more fractioned subgenomes (MFs: MF1 and MF2), while the genes in MF1 were slightly dominantly expressed over the genes in MF2. The results indicated that the dominantly expressed genes tended to be resistant against gene fractionation. By re-sequencing two B. rapa accessions: a vegetable turnip (VT117) and a Rapid Cycling line (L144), we found that genes in LF had less non-synonymous or frameshift mutations than genes in MFs; however mutation rates were not significantly different between MF1 and MF2. The differences in gene expression patterns and on-going gene death among the three subgenomes suggest that “two-step" genome triplication and differential subgenome methylation played important roles in the genome evolution of B. rapa

Research on lamellar structure and micro-hardness of directionally solidified Sn-58Bi eutectic alloy

In this work, the Sn-58Bi (weight percent) eutectic alloy was directionally solidified at a constant temperature gradient (G = 12 K·mm-1) with different growth rates using a Bridgman type directional solidification furnace. A lamellar microstructure was observed in the Sn-58Bi samples. The lamellar spacing and micro-hardness of longitudinal and transversal sections were measured. The values of lamellar spacing of both longitudinal and transversal sections decrease with an increase in growth rate. The microhardness increases with an increase in the growth rate and decreases with an increase in the lamellar spacing. The dependence of lamellar spacing on growth rate, and micro-hardness on both growth rate and lamellar spacing were obtained by linear regression analysis. The relationships between the lamellar spacing and growth rate, microhardness and growth rate, and micro-hardness and lamellar spacing for transversal and longitudinal sections of Sn-58Bi eutectic alloy were given. The fitted exponent values obtained in this work were compared with the previous similar experimental results and a good agreement was obtained

Whole-Exome Sequencing-Based Mutational Profiling of Hepatitis B Virus-Related Early-Stage Hepatocellular Carcinoma

Background. Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortality in China with increasing incidence. This study is designed to explore early genetic changes implicated in HCC tumorigenesis and progression by whole-exome sequencing. Methods. We firstly sequenced the whole exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood samples, followed by gene ontological analysis and pathway analysis of the single-nucleotide variants discovered. Then, the mutations of high frequency were further confirmed by Sanger sequencing. Results. We identified a mutational signature of dominant T:A>A:T transversion in early HCC and significantly enriched pathways including ECM-receptor interaction, axon guidance, and focal adhesion and enriched biological processes containing cell adhesion, axon guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A, DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions. This study reveals a mutational profile and a distinct mutation signature of T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our understanding of genetic characteristics of the early-stage HCC

Number of variants (SNPs+InDels) in different regions of fully retained genes (triplets of homeologs) in the three subgenomes of <i>B. rapa</i>'s cultivar lines L144 and Turnip.

<p>Nonsynonymous SNPs and frameshift InDels in genes from subgenome LF are fewer than those from MFs (p = 9.71E-4, 1.79E-2 for L144; p = 1.74E-11, 1.91E-2 for Turnip). However, no significant differences were observed between MF1 and MF2. Immediately above each bar is the number of variances. Above each group of bars are the <i>p-values</i> of the difference in number of variances between LF and MFs produced by the Fisher exact test (single tail).</p

Biased gene fractionation among the three subgenomes of <i>B. rapa</i>, listed along the 24 AK blocks and the chromosomes of <i>A. thaliana</i>.

a<p> <i>: a χ² test was performed between observed gene numbers and expected gene numbers (equal number of genes retained) among subgenomes.</i></p

Construction of the three subgenomes in <i>B. rapa</i>.

<p>Subgenomes are displayed along the five chromosomes of <i>A. thaliana</i>, with 24 AK blocks painted in different colors, as reported elsewhere <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036442#pone.0036442-Schranz1" target="_blank">[16]</a>. The deep grey chromosome segments denote subgenome LF, while grey and light grey segments denote MF1 and MF2, respectively. The present-day <i>B. rapa</i> chromosomes, such as “A10" from which any segment originates, is labeled to its right. Vertical grey arrows to the left side of block names indicate inverted directions. Horizontal blue lines together with the red arrows indicate identical break regions shared by subgenomes and block boundaries, while black arrows represent identical break regions shared only by subgenomes of <i>B. rapa</i>.</p