1,406 research outputs found

    A Dynamic Classification Approach to Churn Prediction in Banking Industry

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    Churn prediction is the process of using transaction data to identify customers who are likely to cease their relationship with a company. To date, most work in churn prediction focuses on sampling strategies and supervised modeling over a short period of time. Few have explored the area of mining customer behavior pattern in longitudinal data. This research developed a dynamic approach to optimizing model specifications by using time-series predictors, multiple time periods, and rare event detection to enable accurate churn prediction. The study used a unique three-year dataset consisting of 32,000 transaction records of a retail bank in Florida, USA. It uses trend modeling to capture the change of customer behavior over time. Results show that data from multiple time periods helped to improve model precision and recall. This dynamic churn prediction approach can be generalized to other fields for which mining long term customer data is necessary

    Management Options in Triple-Negative Breast Cancer

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    Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date

    Regulation of RNA stability by terminal nucleotidyltransferases

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    The dysregulation of RNAs has global effects on all cellular pathways. The regulation of RNA metabolism is thus tightly controlled. Terminal RNA nucleotidyltransferases (TENTs) regulate RNA stability and activity through the addition of non-templated nucleotides to the 3′-end. TENT-catalyzed adenylation and uridylation have opposing effects; adenylation stabilizes while uridylation silences or degrades RNA. All TENT homologs were initially characterized as adenylyltransferases; the identification of caffeine-induced death suppressor protein 1 (Cid1) in Schizosaccharomyces pombe as an uridylyltransferase led to the reclassification of many TENTs as uridylyltransferases. Cid1 uridylates mRNAs that are subsequently degraded by the exonuclease Dis-like 3′-5′ exonuclease 2 (Dis3L2), while the human homolog germline-development 2 (Gld2) has been associated with adenylation of mRNAs and miRNAs and uridylation of Group II pre-miRNAs. Mechanisms regulating these enzymes and the extent of TENT activity on cellular RNA homeostasis remain largely unknown. In this thesis, the regulation of human Gld2 and the role of the yeast Cid1/Dis3L2-mediated RNA decay pathway were investigated. An enzyme kinetic study revealed that Gld2 is a true adenylyltransferase with only weak activity for UTP. A detailed phylogenetic analysis revealed that uridylyltransferases arose multiple times during evolution through a single histidine insertion in the active site of adenylyltransferases. Insertion of the critical histidine into Gld2 changed its nucleotide preference from ATP to UTP. Next, the regulation of Gld2 through site-specific phosphorylation in the predicted disordered N-terminal domain was investigated using phosphomimetic substitutions at specific serine (S) residues. Two sites (S62, S110) increased Gld2 activity while one site (S116) drastically reduced 3′-adenylation activity. Mass spectrometry and in vitro activity assays identified protein kinases A (PKA) and B (Akt1) as kinases that specifically phosphorylate Gld2 at S116 to obliterate nucleotide addition activity similarly to the S116E phosphomimetic mutant. Finally, RNA deep sequencing of cid1 and dis3L2 S. pombe deletion strains revealed that the role of Cid1 is redundant in uridylation-dependent mRNA decay while Dis3L2 is the bottleneck to RNA decay. Deletion of either gene increases the accumulation of misfolded proteins but only the dis3L2 deletion up-regulates stress response proteins. Overall, this thesis demonstrates how terminal nucleotidyltransferases regulate RNA stability

    Forest Fire Occurrence and Modeling in Southeastern Australia

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    Forest fire is one of the major environmental disturbances for the Australian continent. Identification of occurrence patterns of large fires, fire mapping, determination of fire spreading mechanisms, and fire effect modeling are some of the best measures to plan and mitigate fire effects. This chapter describes fire occurrence in New South Wales (Australia), the Australian National Bushfire Model Project (ANBMP), fire propagation modeling methods, the McArthur’s model and current forest fire modeling approaches in the state of New South Wales of Australia. Among the established fire models, PHOENIX Rapidfire predicts fire spread and facilitates loss and damage assessments as the model considers many environmental and social variables. Two fire spread models, SPARK and Amicus, have been developed and facilitated fire spread mapping and modeling in Australia

    Analysis of Copy Number Variation in the Abp Gene Regions of Two House Mouse Subspecies Suggests Divergence during the Gene Family Expansions

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    The Androgen-binding protein (Abp) gene region of the mouse genome contains 64 genes, some encoding pheromones that influence assortative mating between mice from different subspecies. Using CNVnator and quantitative PCR, we explored copy number variation in this gene family in natural populations of Mus musculus domesticus (Mmd) and Mus musculus musculus (Mmm), two subspecies of house mice that form a narrow hybrid zone in Central Europe. We found that copy number variation in the center of the Abp gene region is very common in wild Mmd, primarily representing the presence/absence of the final duplications described for the mouse genome. Clustering of Mmd individuals based on this variation did not reflect their geographical origin, suggesting no population divergence in the Abp gene cluster. However, copy number variation patterns differ substantially between Mmd and other mouse taxa. Large blocks of Abp genes are absent in Mmm, Mus musculus castaneus and an outgroup, Mus spretus, although with differences in variation and breakpoint locations. Our analysis calls into question the reliance on a reference genome for interpreting the detailed organization of genes in taxa more distant from the Mmd reference genome. The polymorphic nature of the gene family expansion in all four taxa suggests that the number of Abp genes, especially in the central gene region, is not critical to the survival and reproduction of the mouse. However, Abp haplotypes of variable length may serve as a source of raw genetic material for new signals influencing reproductive communication and thus speciation of mice

    Fostering equitable access to higher education in Hong Kong : a study of the tertiary financial assistance scheme

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    published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

    Gld2 activity is regulated by phosphorylation in the N-terminal domain

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    The de-regulation of microRNAs (miRNAs) is associated with multiple human diseases, yet cellular mechanisms governing miRNA abundance remain largely elusive. Human miR-122 is required for Hepatitis C proliferation, and low miR-122 abundance is associated with hepatic cancer. The adenylyltransferase Gld2 catalyses the post-transcriptional addition of a single adenine residue (A + 1) to the 3ʹ-end of miR-122, enhancing its stability. Gld2 activity is inhibited by binding to the Hepatitis C virus core protein during HepC infection, but no other mechanisms of Gld2 regulation are known. We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. The data demonstrate a novel phosphorylation-dependent mechanism to regulate Gld2 activity, revealing tumour suppressor miRNAs as a previously unknown target of Akt1-dependent signalling

    Overcoming Obstacles in Protein Expression in the Yeast Pichia pastoris: Interviews of Leaders in the Pichia Field

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    The yeast Pichia pastoris (also known as Komagataella pastoris) has been used for over 30 years to produce thousands of valuable, heterologous proteins, such as insulin to treat diabetes and antibodies to prevent migraine headaches. Despite its success, there are some common, stubborn problems encountered by research scientists when they try to use the yeast to produce their recombinant proteins. In order to provide those working in this field with strategies to overcome these common obstacles, nine experts in P. pastoris protein expression field were interviewed to create a written review and video (https://www.youtube.com/watch?v=Q1oD6k8CdG8). This review describes how each respected scientist addressed a specific challenge, such as identifying high expression strains, improving secretion efficiency and decreasing hyperglycosylation. Their perspective and practical advice can be a tool to help empower others to express challenging proteins in this popular recombinant host

    Whole Methylome Analysis by Ultra-Deep Sequencing Using Two-Base Encoding

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    Methylation, the addition of methyl groups to cytosine (C), plays an important role in the regulation of gene expression in both normal and dysfunctional cells. During bisulfite conversion and subsequent PCR amplification, unmethylated Cs are converted into thymine (T), while methylated Cs will not be converted. Sequencing of this bisulfite-treated DNA permits the detection of methylation at specific sites. Through the introduction of next-generation sequencing technologies (NGS) simultaneous analysis of methylation motifs in multiple regions provides the opportunity for hypothesis-free study of the entire methylome. Here we present a whole methylome sequencing study that compares two different bisulfite conversion methods (in solution versus in gel), utilizing the high throughput of the SOLiD™ System. Advantages and disadvantages of the two different bisulfite conversion methods for constructing sequencing libraries are discussed. Furthermore, the application of the SOLiD™ bisulfite sequencing to larger and more complex genomes is shown with preliminary in silico created bisulfite converted reads
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