A Second Look at String-Inspired Models for Proton-Proton Scattering via Pomeron Exchange

We re-examine a string dual model for elastic proton-proton scattering via Pomeron exchange. We argue that the method of "Reggeizing" a propagator to take into account an entire trajectory of exchanged particles can be generalized, in particular by modifying the value of the mass-shell parameter in the model. We then fit the generalized model to scattering data at large s and small t. The fitting results are inconclusive, but suggest that a better fit might be obtained by allowing the mass-shell to vary. The model fits the data equally well (roughly) for a wide range of values of the mass-shell parameter, but the other fitting parameters (the slope and intercept of the Regge trajectory, and the coupling constant and dipole mass from the proton-proton-glueball coupling) are then inconsistent with what we expect. On the other hand, using the traditional method of Reggeization generates a weaker fit, but the other parameters obtain more physically reasonable values. In analyzing the fitting results, we also found that our model is more consistent with the sqrt(s) = 1800 GeV coming from the E710 experiment than that coming from the CDF experiment, and that our model has the greatest discrepancy with the data in the range 0.5 GeV^2 < |t| < 0.6 GeV^2, suggesting that the transition from soft Pomeron to hard Pomeron may occur closer to t = -0.5 GeV^2 rather than t = -0.6 GeV^2 as previously thought.Comment: 16 pages, 7 figures, 2 table

Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme

Large-scale screening studies carried out to date for genetic variants that affect gene regulation are generally limited to descriptions of differences in allele-specific expression (ASE) detected in vivo. Allele-specific differences in gene expression provide evidence for a model whereby cis-acting genetic variation results in differential expression between alleles. Such gene surveys for regulatory variation are a first step in identifying the specific nucleotide changes that govern gene expression differences, but they leave the underlying mechanisms unexplored. Here, we propose a quantitative genetics approach to perform a genome-wide analysis of ASE differences (GASED). The GASED approach is based on a diallel design that is often used in plant breeding programs to estimate general combining abilities (GCA) of specific inbred lines and to identify high-yielding hybrid combinations of parents based on their specific combining abilities (SCAs). In a context of gene expression, the values of GCA and SCA parameters allow cis- and trans-regulatory changes to be distinguished and imbalances in gene expression to be ascribed to cis-regulatory variation. With this approach, a total of 715 genes could be identified that are likely to carry allelic polymorphisms responsible for at least a 1.5-fold allelic expression difference in a total of 10 diploid Arabidopsis thaliana hybrids. The major strength of the GASED approach, compared to other ASE detection methods, is that it is not restricted to genes with allelic transcript variants. Although a false-positive rate of 9/41 was observed, the GASED approach is a valuable pre-screening method that can accelerate systematic surveys of naturally occurring cis-regulatory variation among inbred lines for laboratory species, such as Arabidopsis, mouse, rat and fruitfly, and economically important crop species, such as corn

A Retrotransposon Insertion in the 5' Regulatory Domain of Ptf1a Results in Ectopic Gene Expression and Multiple Congenital Defects in Danforth’s Short Tail Mouse

Danforth's short tail mutant (Sd) mouse, first described in 1930, is a classic spontaneous mutant exhibiting defects of the axial skeleton, hindgut, and urogenital system. We used meiotic mapping in 1,497 segregants to localize the mutation to a 42.8-kb intergenic segment on chromosome 2. Resequencing of this region identified an 8.5-kb early retrotransposon (ETn) insertion within the highly conserved regulatory sequences upstream of Pancreas Specific Transcription Factor, 1a (Ptf1a). This mutation resulted in up to tenfold increased expression of Ptf1a as compared to wild-type embryos at E9.5 but no detectable changes in the expression levels of other neighboring genes. At E9.5, Sd mutants exhibit ectopic Ptf1a expression in embryonic progenitors of every organ that will manifest a developmental defect: the notochord, the hindgut, and the mesonephric ducts. Moreover, at E 8.5, Sd mutant mice exhibit ectopic Ptf1a expression in the lateral plate mesoderm, tail bud mesenchyme, and in the notochord, preceding the onset of visible defects such as notochord degeneration. The Sd heterozygote phenotype was not ameliorated by Ptf1a haploinsufficiency, further suggesting that the developmental defects result from ectopic expression of Ptf1a. These data identify disruption of the spatio-temporal pattern of Ptf1a expression as the unifying mechanism underlying the multiple congenital defects in Danforth's short tail mouse. This striking example of an enhancer mutation resulting in profound developmental defects suggests that disruption of conserved regulatory elements may also contribute to human malformation syndromes

Contribution of trans regulatory eQTL to cryptic genetic variation in C-elegans

BackgroundCryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population.ResultsWe measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly shared across treatments. A considerable fraction of the trans-eQTL (40–57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL.ConclusionsThese results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 h) and that CGV is mainly determined by response related trans regulatory eQTL.<br/

PIXAPP Photonics Packaging Pilot Line development of a silicon photonic optical transceiver with pluggable fiber connectivity

This paper demonstrates how the PIXAPP Photonics Packaging Pilot Line uses its extensive packaging capabilities across its European partner network to design and assemble a highly integrated silicon photonic-based optical transceiver. The processes used are based on PIXAPP's open access packaging design rules or Assembly Design Kit (ADK). The transceiver was designed to have the Tx and Rx elements integrated on to a single silicon photonic chip, together with flipchip control electronics, hybrid laser and micro-optics. The transceiver used the on-chip micro-optics to enable a pluggable fiber connection, avoiding the need to bond optical fibers directly to the photonic chip. Finally, the packaged transceiver module was tested, showing 56 Gb/s loop-back modulation and de-modulation, validating both the transmitter and receiver performance

Complementary approaches to find functional molecular variation in the core cell cycle genes of Arabidopsis

Unraveling the genetic networks underlying natural variation of quantitative traits is a challenging task. The initial research goal of this thesis was to identify quantitative trait loci (QTL) that underlie the natural variation of biomass production in Arabidopsis thaliana. One approach to analyze quantitative traits is by using genome-wide association or linkage disequilibrium (LD)-based mapping. At the time when this project was conceived, it was claimed that LD in A. thaliana extended up to 250 kb and that allelic diversity was limited (Nordborg et al. 2002). Under this assumption, it would be feasible to do successful association analysis in A. thaliana with ~2000 evenly spaced genome-wide markers in a sample of 96 accessions. Therefore, we wanted to adopt this association strategy to elucidate the genetic determinants underlying natural variation of biomass in A. thaliana. Subsequently, the aim of the first part of this thesis (Chapter 2-3) was to asses the feasibility of the genome-wide association strategy and to establish the tools and data sets eventually required. Chapter two describes the analysis of natural variation of biomass production in A. thaliana in a sample of ~90 accessions. Chapter three describes the analysis of LD extent in A. thaliana. We wanted to independently validate the findings of Nordborg et al. (2002) on a genome-wide scale using AFLP generated markers and publicly available SNP markers. Conclusions from both chapter 2 and 3 however showed that the preconceived assumptions were unfounded, making a genome-wide association strategy to map biomass production QTLs currently impracticable. Given the conclusions from the first part of this thesis, we chose to re-orient our research strategy towards candidate gene approaches to identify functional molecular variation. The mitotic cell cycle is a much studied biological system in A. thaliana and the cell cycle has a central role in the development, differentiation and proliferation of plant organs. Given that the genes controlling the cell cycle progression have been identified and that many cell cycle related traits show natural variation, we selected the core cell cycle (CCC) genes of A. thaliana as candidate genes in our further approaches. In addition, we focused the natural variation studies on endoreduplication and root cortical cell length, because these phenotypes are directly controlled by the cell cycle regulation and easier to measure than biomass variation. Introduction 33 Chapter four describes a population genetics approach to assess if particular CCC genes have been affected by selective constraint or by directional positive selection, either directly or through linkage, as opposed to neutral evolutionary forces. When the neutral evolution hypothesis can be rejected, it can be that the CCC genes, or the region they are located in, contain genetic variants that affect phenotypic variation of adaptive traits. In chapter five we used a candidate gene association approach to find associations between haplotypes of CCC genes and natural variation in two cell cycle related phenotypes: endoreduplication and root cortical cell length. Finally, in chapter six, we summarize and discuss the conclusions and future prospects of the work described in this thesis

The genetics of albuminuria: from haplotype association mapping in mice to genetic causation in humans

Genome-wide haplotype association mapping (HAM) in inbred mouse strains emerged as an efficient method for identifying novel quantitative trait loci for disease-related phenotypes. In this issue of Kidney International, Tsaih et al. present the results of the first HAM for age-related kidney damage in mice and examine the detected loci in the context of the human genome-wide association study for diabetic nephropathy

Dissecting the eQTL Micro-Architecture in Caenorhabditis elegans

The study of expression quantitative trait loci (eQTL) using natural variation in inbred populations has yielded detailed information about the transcriptional regulation of complex traits. Studies on eQTL using recombinant inbred lines (RILs) led to insights on cis and trans regulatory loci of transcript abundance. However, determining the underlying causal polymorphic genes or variants is difficult, but ultimately essential for the understanding of regulatory networks of complex traits. This requires insight into whether associated loci are single eQTL or a combination of closely linked eQTL, and how this QTL micro-architecture depends on the environment. We addressed these questions by testing for independent replication of previously mapped eQTL in Caenorhabditis elegans using new data from introgression lines (ILs). Both populations indicate that the overall heritability of gene expression, number, and position of eQTL differed among environments. Across environments we were able to replicate 70% of the cis- and 40% of the trans-eQTL using the ILs. Testing eight different simulation models, we suggest that additive effects explain up to 60–93% of RIL/IL heritability for all three environments. Closely linked eQTL explained up to 40% of RIL/IL heritability in the control environment whereas only 7% in the heat-stress and recovery environments. In conclusion, we show that reproducibility of eQTL was higher for cis vs. trans eQTL and that the environment affects the eQTL micro-architecture

A Population Genomics Study of the Arabidopsis Core Cell Cycle Genes Shows the Signature of Natural Selection[W]

Large-scale comparison of sequence polymorphism and divergence at numerous genomic loci within and between closely related species can reveal signatures of natural selection. Here, we present a population genomics study based on direct sequencing of 61 mitotic cell cycle genes from 30 Arabidopsis thaliana accessions and comparison of the resulting data to the close relative Arabidopsis lyrata. We found that the Arabidopsis core cell cycle (CCC) machinery is not highly constrained but is subject to different modes of selection. We found patterns of purifying selection for the cyclin-dependent kinase (CDK), CDK subunit, retinoblastoma, and WEE1 gene families. Other CCC gene families often showed a mix of one or two constrained genes and relaxed purifying selection on the other genes. We found several large effect mutations in CDKB1;2 that segregate in the species. We found a strong signature of adaptive protein evolution in the Kip-related protein KRP6 and departures from equilibrium at CDKD;1 and CYCA3;3 consistent with the operation of selection in these gene regions. Our data suggest that within Arabidopsis, the genetic robustness of cell cycle–related processes is more due to functional redundancy than high selective constraint

Dissecting the eQTL Micro-Architecture in Caenorhabditis elegans

The study of expression quantitative trait loci (eQTL) using natural variation in inbred populations has yielded detailed information about the transcriptional regulation of complex traits. Studies on eQTL using recombinant inbred lines (RILs) led to insights on cis and trans regulatory loci of transcript abundance. However, determining the underlying causal polymorphic genes or variants is difficult, but ultimately essential for the understanding of regulatory networks of complex traits. This requires insight into whether associated loci are single eQTL or a combination of closely linked eQTL, and how this QTL micro-architecture depends on the environment. We addressed these questions by testing for independent replication of previously mapped eQTL in C. elegans using new data from introgression lines (ILs). Both populations indicate that the overall heritability of gene expression, number, and position of eQTL differed among environments. Across environments we were able to replicate 70% of the cis- and 40% of the trans-eQTL using the ILs. Testing eight different simulation models, we suggest that additive effects explain up to 60-93% of RIL/IL heritability for all three environments. Closely linked eQTL explained up to 40% of RIL/IL heritability in the control environment whereas only 7% in the heat-stress and recovery environments. In conclusion, we show that reproducibility of eQTL was higher for cis vs. trans eQTL and that the environment affects the eQTL micro-architecture