Local partial likelihood estimation in proportional hazards regression

Fan, Gijbels and King [Ann. Statist. 25 (1997) 1661--1690] considered the estimation of the risk function $\psi (x)$ in the proportional hazards model. Their proposed estimator is based on integrating the estimated derivative function obtained through a local version of the partial likelihood. They proved the large sample properties of the derivative function, but the large sample properties of the estimator for the risk function itself were not established. In this paper, we consider direct estimation of the relative risk function $\psi (x_2)-\psi (x_1)$ for any location normalization point $x_1$. The main novelty in our approach is that we select observations in shrinking neighborhoods of both $x_1$ and $x_2$ when constructing a local version of the partial likelihood, whereas Fan, Gijbels and King [Ann. Statist. 25 (1997) 1661--1690] only concentrated on a single neighborhood, resulting in the cancellation of the risk function in the local likelihood function. The asymptotic properties of our estimator are rigorously established and the variance of the estimator is easily estimated. The idea behind our approach is extended to estimate the differences between groups. A simulation study is carried out.Comment: Published at http://dx.doi.org/10.1214/009053606000001299 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Group-Heterogeneous Changes-in-Changes and Distributional Synthetic Controls

We develop new methods for changes-in-changes and distributional synthetic controls when there exists group level heterogeneity. For changes-in-changes, we allow individuals to belong to a large number of heterogeneous groups. The new method extends the changes-in-changes method in Athey and Imbens (2006) by finding appropriate subgroups within the control groups which share similar group level unobserved characteristics to the treatment groups. For distributional synthetic control, we show that the appropriate synthetic control needs to be constructed using units in potentially different time periods in which they have comparable group level heterogeneity to the treatment group, instead of units that are only in the same time period as in Gunsilius (2023). Implementation and data requirements for these new methods are briefly discussed

Crosstalk Impacts on Homogeneous Weakly-Coupled Multicore Fiber Based IM/DD System

We numerically discussed crosstalk impacts on homogeneous weakly-coupled multicore fiber based intensity modulation/direct-detection (IM/DD) systems taking into account mean crosstalk power fluctuation, walk-off between cores, laser frequency offset, and laser linewidth.Comment: 3 pages, 11 figures

Differential gene expression in an elite hybrid rice cultivar (Oryza sativa, L) and its parental lines based on SAGE data

<p>Abstract</p> <p>Background</p> <p>It was proposed that differentially-expressed genes, aside from genetic variations affecting protein processing and functioning, between hybrid and its parents provide essential candidates for studying heterosis or hybrid vigor. Based our serial analysis of gene expression (SAGE) data from an elite Chinese super-hybrid rice (<it>LYP9</it>) and its parental cultivars (<it>93-11 </it>and <it>PA64s</it>) in three major tissue types (leaves, roots and panicles) at different developmental stages, we analyzed the transcriptome and looked for candidate genes related to rice heterosis.</p> <p>Results</p> <p>By using an improved strategy of tag-to-gene mapping and two recently annotated genome assemblies (<it>93-11 and PA64s</it>), we identified 10,268 additional high-quality tags, reaching a grand total of 20,595 together with our previous result. We further detected 8.5% and 5.9% physically-mapped genes that are differentially-expressed among the triad (in at least one of the three stages) with <it>P</it>-values less than 0.05 and 0.01, respectively. These genes distributed in 12 major gene expression patterns; among them, 406 up-regulated and 469 down-regulated genes (<it>P </it>< 0.05) were observed. Functional annotations on the identified genes highlighted the conclusion that up-regulated genes (some of them are known enzymes) in hybrid are mostly related to enhancing carbon assimilation in leaves and roots. In addition, we detected a group of up-regulated genes related to male sterility and 442 down-regulated genes related to signal transduction and protein processing, which may be responsible for rice heterosis.</p> <p>Conclusion</p> <p>We improved tag-to-gene mapping strategy by combining information from transcript sequences and rice genome annotation, and obtained a more comprehensive view on genes that related to rice heterosis. The candidates for heterosis-related genes among different genotypes provided new avenue for exploring the molecular mechanism underlying heterosis.</p

A gene catalogue for post-diapause development of an anhydrobiotic arthropod Artemia franciscana

<p>Abstract</p> <p>Background</p> <p>Diapause is a reversible state of developmental suspension and found among diverse taxa, from plants to animals, including marsupials and some other mammals. Although previous work has accumulated ample data, the molecular mechanism underlying diapause and reactivation from it remain elusive.</p> <p>Results</p> <p>Using <it>Artemia franciscana</it>, a model organism to study the development of post-diapause embryos in Arthropod, we sequenced random clones up to a total of 28,039 ESTs from four cDNA libraries made from dehydrated cysts and three time points after rehydration/reactivation, which were assembled into 8,018 unigene clusters. We identified 324 differentially-expressed genes (DEGs, <it>P </it>< 0.05) based on pairwise comparisons of the four cDNA libraries. We identified a group of genes that are involved in an anti-water-deficit system, including proteases, protease inhibitors, heat shock proteins, and several novel members of the late embryogenesis abundant (LEA) protein family. In addition, we classified most of the up-regulated genes after cyst reactivation into metabolism, biosynthesis, transcription, and translation, and this result is consistent with the rapid development of the embryo. Some of the specific expressions of DEGs were confirmed experimentally based on quantitative real-time PCR.</p> <p>Conclusion</p> <p>We found that the first 5-hour period after rehydration is most important for embryonic reactivation of <it>Artemia</it>. As the total number of expressed genes increases significantly, the majority of DEGs were also identified in this period, including a group of water-deficient-induced genes. A group of genes with similar functions have been described in plant seeds; for instance, one of the novel LEA members shares ~70% amino-acid identity with an <it>Arabidopsis </it>EM (embryonic abundant) protein, the closest animal relative to plant LEA families identified thus far. Our findings also suggested that not only nutrition, but also mRNAs are produced and stored during cyst formation to support rapid development after reactivation.</p

Transcriptome and expression profiling analysis revealed changes of multiple signaling pathways involved in immunity in the large yellow croaker during Aeromonas hydrophila infection

<p>Abstract</p> <p>Background</p> <p>The large yellow croaker (<it>Pseudosciaena crocea</it>) is an economically important marine fish in China suffering from severe outbreaks of infectious disease caused by marine bacteria such as <it>Aeromonas hydrophila </it>(<it>A. hydrophila</it>), resulting in great economic losses. However, the mechanisms involved in the immune response of this fish to bacterial infection are not fully understood. To understand the molecular mechanisms underlying the immune response to such pathogenic bacteria, we used high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of the large yellow croaker infected with <it>A. hydrophila</it>.</p> <p>Results</p> <p>A total of 13,611,340 reads were obtained and assembled into 26,313 scaffolds in transcriptional responses of the <it>A. hydrophila</it>-infected large yellow croaker. Via annotation to the NCBI database, we obtained 8216 identified unigenes. In total, 5590 (68%) unigenes were classified into Gene Ontology, and 3094 unigenes were found in 20 KEGG categories. These genes included representatives from almost all functional categories. By using Solexa/Illumina's DeepSAGE, 1996 differentially expressed genes (P value < 0.05) were detected in comparative analysis of the expression profiles between <it>A. hydrophila</it>-infected fish and control fish, including 727 remarkably upregulated genes and 489 remarkably downregulated genes. Dramatic differences were observed in genes involved in the inflammatory response. Bacterial infection affected the gene expression of many components of signaling cascades, including the Toll-like receptor, JAK-STAT, and MAPK pathways. Genes encoding factors involved in T cell receptor (TCR) signaling were also revealed to be regulated by infection in these fish.</p> <p>Conclusion</p> <p>Based on our results, we conclude that the inflammatory response may play an important role in the early stages of infection. The signaling cascades such as the Toll-like receptor, JAK-STAT, and MAPK pathways are regulated by <it>A. hydrophila </it>infection. Interestingly, genes encoding factors involved in TCR signaling were revealed to be downregulated by infection, indicating that TCR signaling was suppressed at this early period. These results revealed changes of multiple signaling pathways involved in immunity during <it>A. hydrophila </it>infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in the large yellow croaker.</p

Transcriptomic profiling of mature embryo from an elite super-hybrid rice LYP9 and its parental lines

<p>Abstract</p> <p>Background</p> <p>The mature embryo of rice (<it>Oryza sativa, L</it>.) is a synchronized and integrated tissue mass laying the foundation at molecular level for its growth, development, and differentiation toward a developing and ultimately a mature plant. We carried out an EST (expressed-sequence-tags)-based transcriptomic study, aiming at gaining molecular insights into embryonic development of a rice hybrid triad–an elite hybrid rice <it>LYP</it>9 and its parental lines (<it>93-11 </it>and <it>PA64s</it>)–and possible relatedness to heterosis.</p> <p>Results</p> <p>We generated 27,566 high-quality ESTs from cDNA libraries made from mature rice embryos. We classified these ESTs into 7,557 unigenes (2,511 contigs and 5,046 singletons) and 7,250 (95.9%) of them were annotated. We noticed that the high-abundance genes in mature rice embryos belong to two major functional categories, stress-tolerance and preparation-for-development, and we also identified 191 differentially-expressed genes (General Chi-squared test, <it>P</it>-value <= 0.05) between <it>LYP9 </it>and its parental lines, representing typical expression patterns including over-dominance, high- and low-parent dominance, additivity, and under-dominance. In <it>LYP9</it>, the majority of embryo-associated genes were found not only abundantly and specifically enriched but also significantly up-regulated.</p> <p>Conclusion</p> <p>Our results suggested that massively strengthening tissue-(or stage-) characteristic functions may contribute to heterosis rather than a few simple mechanistic explanations at the individual gene level. In addition, the large collection of rice embryonic ESTs provides significant amount of data for future comparative analyses on plant development, especially for the important crops of the grass family.</p

Complete Genome and Transcriptomes of Streptococcus parasanguinis FW213: Phylogenic Relations and Potential Virulence Mechanisms

Streptococcus parasanguinis, a primary colonizer of the tooth surface, is also an opportunistic pathogen for subacute endocarditis. The complete genome of strain FW213 was determined using the traditional shotgun sequencing approach and further refined by the transcriptomes of cells in early exponential and early stationary growth phases in this study. The transcriptomes also discovered 10 transcripts encoding known hypothetical proteins, one pseudogene, five transcripts matched to the Rfam and additional 87 putative small RNAs within the intergenic regions defined by the GLIMMER analysis. The genome contains five acquired genomic islands (GIs) encoding proteins which potentially contribute to the overall pathogenic capacity and fitness of this microbe. The differential expression of the GIs and various open reading frames outside the GIs at the two growth phases suggested that FW213 possess a range of mechanisms to avoid host immune clearance, to colonize host tissues, to survive within oral biofilms and to overcome various environmental insults. Furthermore, the comparative genome analysis of five S. parasanguinis strains indicates that albeit S. parasanguinis strains are highly conserved, variations in the genome content exist. These variations may reflect differences in pathogenic potential between the strains

Development And Testing Of Data Driven Nowcasting Models Of Beach Water Quality

Beach water issues are gaining worldwide attention due to their impact on health and other environmental problems. The Ontario beaches require beach managers to issue swimming advisories when water quality standards are exceeded since users of recreational waters may be exposed to elevated pathogen levels through various point and non-point sources. Typical daily notifications rely on microbial analysis of indicator organisms (e.g. Escherichia coli), which require 18-24 hours to provide an adequate response. This research evaluated the use of Artificial Neural Networks (ANNs) and Evolutionary Polynomial Regression (EPR) for real time prediction of E.coli in the beach waters of Toronto (Ontario, Canada). The nowcasting models were developed in combination with readily available real-time environmental and hydro-meteorological data during the bathing season (June-August) of 2008 to 2012 for Toronto’s three beaches. The performance of ANN and EPR models was assessed in terms of their ability to accurately match observed E.coli concentrations and to correctly predict when the beach water quality standard - primary contact recreation of 100 CFU/ 100 ml - is exceeded. In the ANN models the feed forward back propagation algorithm was used for the analysis. Different combinations of predictor variables were used and the best results were obtained when stream flow, various combinations of antecedent rainfalls, lake level, solar radiation, past counts of E.coli, wind direction and speed were used. The results of the developed models were compared with those of the conventional method and statistical models, and it was found that the predictions of ANN models slightly outperforms with better accuracy. The best performing ANN models on each beach are able to predict approximately 60% to 90% of the E.coli concentrations, whereas the EPR models return a correct prediction as high as 77%. The developed methodologies offer a promising alternative to traditional methods for the protection of health in bathing beaches