Mesoscale analysis by numerical modeling coupled with satellite-based sounding

November 1988.Principal investigators: Thomas H. Vonder Haar, James F.W. Purdom.Includes bibliographical references.This dissertation deals with the development of a system for time-continuous mesoscale analysis and its use in studying the mesoscale distribution of summertime convective cloud development in the Northeastern Colorado region. There were two basic components of the system — a version of the CSU Regional Atmospheric Modeling System (RAMS) and an algorithm for retrieving temperatures and water vapor concentrations from VISSR Atmospheric Sounder (VAS) data. The system was designed to avoid some of the problems that researchers have encountered when satellite-retrieved parameters have been input to models. The primary distinguishing feature of the new method is that there is an intimate coupling of the retrieval and modeling processes. Water vapor concentrations and ground surface temperatures were the foci of the analyses. In preparation for analysis experiments we tested the sensitivity of a two-dimensional version of the model to various controls on the behavior of water vapor concentrations and surface temperatures. For water vapor mixing ratios, variations that might be caused by analysis errors had very little impact on the dynamics of circulations in the pre-convective stage. In contrast, ground surface temperature variations were shown to have a large impact on circulations, so analysis errors are very relevant to pre-convective dynamics. The first comparisons of the coupled analysis method with other, related, methods was by means of two-dimensional simulations. Analyses in which surface temperatures were derived from satellite-retrievals were compared with the alternative of relying on energy balance computations. The energy balance computations were so sensitive to soil characteristics, which were simulated as unknown, that the satellite retrieval method gave better results even with cloud contamination. In water vapor analysis comparisons no single method was superior in every respect, but the coupled method performed relatively well. Vertical gradients and horizontal gradients were well represented, and the method was relatively insensitive to a common problem in pre-convective analysis — contamination of satellite data by increasing amounts of small convective clouds. Analysis methods were further compared in a three-dimensional case study for 21 August 1983. The horizontal and time variations of satellite-retrieved surface temperatures closely corresponded to the conventional shelter temperature observations, but had much greater detail. In contrast, the energy balance-based temperatures tended to increase too quickly during the morning and lacked some of the observed gradients. According to the retrievals, there can be very large mesoscale gradients in temperatures at the ground surface even on the relatively flat plains. In the case study water vapor analyses there were substantial differences among the results of the several methods that were intercompared. The study demonstrated that, when the first set of satellite data is less reliable than the later sets, some of the contamination lingers throughout the time-continuous coupled analysis results. However, the coupled method generally appeared to be the most valuable of the methods considered in this study because it exploited the major strengths of the numerical model and the satellite data while making it relatively easy to recognize any impacts of their weaknesses. The results of this dissertation support the hypothesis that both ground surface temperatures and terrain variations can play important roles in pre-convective water vapor kinematics through their influences on vertical and horizontal winds. The development of convective clouds corresponded largely, but not exclusively, with convergence and deepening of low-level water vapor. The analysis system proved to be valuable for forecasting through the close correspondence between derived stability indices and later convective development. The new method is a step in the expanding capability of meteorologists to combine tools and sources of data for understanding and forecasting mesoscale phenomena.Research supported by National Oceanic and Atmospheric Administration Grant NA-85-RAH-05045 (53-1209) and in part by Army Research Office Center for Geosciences, Grant DALL-03-86-K-9175

Genetic analysis of enzyme polymorphisms in plaice (Pleuronectes platessa)

Genetic analysis was performed on five enzyme systems (G3PDH; GPI-A; GPI-B; PGM; MDH-A) in plaice (Pleuronectes platessa) collected in spawning condition from the North Sea. Conventional crosses, induced gynogenesis and induced triploidy were performed. The data conclusively demonstrated the inheritance of isozymes by co-dominant alleles at individual loci for each system. No linkage was observed but tests did not include MDH nor the possibility of linkage between G3PDH and GPI-A. Some anomalous segregation ratios were observed, particularly a deficiency of heterozygotes for GPI-A, but the data were largely in conformity with Mendelian expectations. At the PGM locus, five independent anomalous individuals were scored and interpreted as mutations with a mutation rate of 1·1 × 10−3 per gamete. Recombination with the centromere was assessed and induced triploidy and cross-over values of 41 per cent for PGM, 19 per cent for MDH-A and 9 per cent for GPI-B were derived on the assumption of complete interference. Amongst the parent fish, genotypic and phenotypic frequencies were largely consistent with the expectations of the Hardy-Weinberg Law, and allelic frequencies were not significantly different between year of collection or location of collection ground

Determination of steroid estrogens in wastewater by high performance liquid chromatography-tandem mass spectrometry

This paper discusses the requirement for, and presents an analytical procedure for, the determination of four unconjugated steroid hormones and a conjugated steroid (estrone-3-sulfate) in wastewaters. The method quantifies the steroids by LC/MS/MS following solid phase extraction and a two stage clean-up procedure. Samples were extracted using C18 cartridges and eluates were then purified by gel permeation chromatography, followed by a further clean-up step on an aminopropyl cartridge. The limits of detection achieved were 0.2 ng l-1 for estriol, 17β-estradiol and 17α-ethinylestradiol, and 0.1 ng l-1 for estrone and the conjugate. The robustness of the method was demonstrated by achieving recoveries of >83% for all steroids in settled sewage and final effluent samples with relative standard deviations of 0.5 - 12%. The method was used to analyse a range of samples from a wastewater treatment works in south east England which demonstrated a >80% removal for estrone, estradiol and estriol with little impact on concentrations of ethinylestradiol or the conjugate

Seminar on Evidence and Trial Practice

Outlines of speaker presentations offered during a series of one day seminars on evidence and trial practice offered by UK/CLE in late 1987-early 1988

Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

Pregnancy-induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study

Background: Little is known about gene expression changes induced by pregnancy in women with rheumatoid arthritis (RA) and healthy women because the few studies previously conducted did not have pre-pregnancy samples available as baseline. We have established a cohort of women with RA and healthy women followed prospectively from a pre-pregnancy baseline. In this study, we tested the hypothesis that pregnancy-induced changes in gene expression among women with RA who improve during pregnancy (pregDAS_(improved)) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDAS_(worse)). Methods: Global gene expression profiles were generated by RNA sequencing (RNA-seq) from 11 women with RA and 5 healthy women before pregnancy (T0) and at the third trimester (T3). Among the women with RA, eight showed an improvement in disease activity by T3, whereas three worsened. Differential expression analysis was used to identify genes demonstrating significant changes in expression within each of the RA and healthy groups (T3 vs T0), as well as between the groups at each time point. Gene set enrichment was assessed in terms of Gene Ontology processes and protein networks. Results: A total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDAS_(improved) women, with 161 genes showing at least two-fold change (FC) in expression by T3. The majority (108 of 161 genes) were also differentially expressed among healthy women (q<0.05, FC≥2). Additionally, a small cluster of genes demonstrated contrasting changes in expression between the pregDAS_(improved) and pregDAS_(worse) groups, all of which were inducible by type I interferon (IFN). These IFN-inducible genes were over-expressed at T3 compared to the T0 baseline among the pregDAS_(improved) women. Conclusions: In our pilot RNA-seq dataset, increased pregnancy-induced expression of type I IFN-inducible genes was observed among women with RA who improved during pregnancy, but not among women who worsened. These findings warrant further investigation into expression of these genes in RA pregnancy and their potential role in modulation of disease activity. These results are nevertheless preliminary and should be interpreted with caution until replicated in a larger sample

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk