Solutions to problems of nonexistence of parameter estimates and sparse data bias in Poisson regression.

Poisson regression can be challenging with sparse data, in particular with certain data constellations where maximum likelihood estimates of regression coefficients do not exist. This paper provides a comprehensive evaluation of methods that give finite regression coefficients when maximum likelihood estimates do not exist, including Firth's general approach to bias reduction, exact conditional Poisson regression, and a Bayesian estimator using weakly informative priors that can be obtained via data augmentation. Furthermore, we include in our evaluation a new proposal for a modification of Firth's approach, improving its performance for predictions without compromising its attractive bias-correcting properties for regression coefficients.

Quorum Sensing and Cyclic di-GMP Exert Control Over Motility of KB2B1.

Bacterial motility is critical for symbiotic colonization by of its host, the squid , facilitating movement from surface biofilms to spaces deep inside the symbiotic organ. While colonization has been studied traditionally using strain ES114, others, including KB2B1, can outcompete ES114 for colonization for a variety of reasons, including superior biofilm formation. We report here that KB2B1 also exhibits an unusual pattern of migration through a soft agar medium: whereas ES114 migrates rapidly and steadily, KB2B1 migrates slowly and then ceases migration.

A High-Throughput Method for Identifying Novel Genes That Influence Metabolic Pathways Reveals New Iron and Heme Regulation in Pseudomonas aeruginosa.

Heme is an essential metabolite for most life on earth. Bacterial pathogens almost universally require iron to infect a host, often acquiring this nutrient in the form of heme. The Gram-negative pathogen is no exception, where heme acquisition and metabolism are known to be crucial for both chronic and acute infections.

Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.

3-Hydroxy-3-methylglutaryl coenzyme A reductase is associated with monitoring cholesterol levels. The presence of the single-nucleotide polymorphism rs3846662 introduces alternative splicing at exon 13; the exclusion of this exon leads to a reduction in total cholesterol levels. Lower cholesterol levels are linked to a reduction in Alzheimer's disease (AD) risk.

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry.

Importance: Some of the unexplained heritability of Alzheimer disease (AD) may be due to rare variants whose effects are not captured in genome-wide association studies because very large samples are needed to observe statistically significant associations.

Objective: To identify genetic variants associated with AD risk using a nonstatistical approach.

Design, Setting, And Participants: Genetic association study in which rare variants were identified by whole-exome sequencing in unrelated individuals of European ancestry from the Alzheimer's Disease Sequencing Project (ADSP).

Common DNA Variants Accurately Rank an Individual of Extreme Height.

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype.

Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.

Background: While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.

Methods: We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths.

Presenilin E318G variant and Alzheimer's disease risk: the Cache County study.

Background: Alzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer's disease, including Presenilin 1 (PSEN1). Multiple studies have attempted to locate novel variants in the PSEN1 gene that affect Alzheimer's disease status.

Involvement of condensin-directed gene associations in the organization and regulation of chromosome territories during the cell cycle.

Chromosomes are not randomly disposed in the nucleus but instead occupy discrete sub-nuclear domains, referred to as chromosome territories. The molecular mechanisms that underlie the formation of chromosome territories and how they are regulated during the cell cycle remain largely unknown. Here, we have developed two different chromosome-painting approaches to address how chromosome territories are organized in the fission yeast model organism.

A forest-based feature screening approach for large-scale genome data with complex structures.

Background: Genome-wide association studies (GWAS) interrogate large-scale whole genome to characterize the complex genetic architecture for biomedical traits. When the number of SNPs dramatically increases to half million but the sample size is still limited to thousands, the traditional p-value based statistical approaches suffer from unprecedented limitations. Feature screening has proved to be an effective and powerful approach to handle ultrahigh dimensional data statistically, yet it has not received much attention in GWAS.

Exploiting Linkage Disequilibrium for Ultrahigh-Dimensional Genome-Wide Data with an Integrated Statistical Approach.

Genome-wide data with millions of single-nucleotide polymorphisms (SNPs) can be highly correlated due to linkage disequilibrium (LD). The ultrahigh dimensionality of big data brings unprecedented challenges to statistical modeling such as noise accumulation, the curse of dimensionality, computational burden, spurious correlations, and a processing and storing bottleneck. The traditional statistical approaches lose their power due to [Formula: see text] (n is the number of observations and p is the number of SNPs) and the complex correlation structure among SNPs.

Incorporation of subject-level covariates in quantile normalization of miRNA data.

Background: Most currently-used normalization methods for miRNA array data are based on methods developed for mRNA arrays despite fundamental differences between the data characteristics. The application of conventional quantile normalization can mask important expression differences by ignoring demographic and environmental factors. We present a generalization of the conventional quantile normalization method, making use of available subject-level covariates in a colorectal cancer study.

Interaction between TBP and Condensin Drives the Organization and Faithful Segregation of Mitotic Chromosomes.

Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres.

Accounting for dependence induced by weighted KNN imputation in paired samples, motivated by a colorectal cancer study.

Missing data can arise in bioinformatics applications for a variety of reasons, and imputation methods are frequently applied to such data. We are motivated by a colorectal cancer study where miRNA expression was measured in paired tumor-normal samples of hundreds of patients, but data for many normal samples were missing due to lack of tissue availability. We compare the precision and power performance of several imputation methods, and draw attention to the statistical dependence induced by K-Nearest Neighbors (KNN) imputation.

Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study.

Objective: Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group.

Methods: We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating sum of boxes scores over time.

Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: the Cache County Study.

Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment.

Population substructure in Cache County, Utah: the Cache County study.

Background: Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Mitochondrial genomic variation associated with higher mitochondrial copy number: the Cache County Study on Memory Health and Aging.

Background: The mitochondria are essential organelles and are the location of cellular respiration, which is responsible for the majority of ATP production. Each cell contains multiple mitochondria, and each mitochondrion contains multiple copies of its own circular genome. The ratio of mitochondrial genomes to nuclear genomes is referred to as mitochondrial copy number.

Printing-based assembly of quadruple-junction four-terminal microscale solar cells and their use in high-efficiency modules.

Expenses associated with shipping, installation, land, regulatory compliance and on-going maintenance and operations of utility-scale photovoltaics can be significantly reduced by increasing the power conversion efficiency of solar modules through improved materials, device designs and strategies for light management. Single-junction cells have performance constraints defined by their Shockley-Queisser limits. Multi-junction cells can achieve higher efficiencies, but epitaxial and current matching requirements between the single junctions in the devices hinder progress.

Passive coherent combination of a diode laser array with 35 elements.

A monolithic diode laser array with 35 elements is operated as a coherent array through the use of a Self-Fourier cavity. By analyzing the far field interference pattern, the coherence was measured to be 0.57 with all 35 elements operating and was measured to be approximately constant for arrays with greater than 15 elements.

Effect of Kerr and resonant nonlinearities on phase locking of a multistable fiber amplifier array.

An analysis is presented, based on a rigorous solution of the propagation equations, of an array of saturable fiber amplifiers with scatter in length that is subject to global feedback. Passively phase-locked states exhibiting multistability due to resonant or Kerr nonlinearity are predicted in respectively low and high regimes of optical feedback.

Enhanced ultraviolet responses in thin-film InGaP solar cells by down-shifting.

Layers of poly(methyl methacrylate) doped with the Eu complex Eu(DPEPO)(hfac)3 (EuDH) provide a means for down-shifting incident ultraviolet (UV) light into the visible range, with beneficial effects on the performance of solar cells, as demonstrated with thin-film InGaP devices formed by epitaxial liftoff. Experimental and computational results establish important aspects of gain and loss mechanisms in the UV range. Measurements show that InGaP cells with coatings of EuDH doped PMMA exhibit enhanced currents (8.