Angles and Quasiconformal Mappings†

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135391/1/plms0001.pd

Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Along-strike variations of P-T conditions in accretionary wedges and syn-orogenic extension, the HP-LT Phyllite-Quartzite Nappe in Crete and the Peloponnese

International audienceSyn-orogenic detachments in accretionary wedges make the exhumation of high-pressure and low-temperature metamorphic rocks possible with little erosion. The velocity of exhumation within the subduction channel or the accretionary complex, and thus the shape of P-T paths, depend upon the kinematic boundary conditions. A component of slab retreat tends to open the channel and facilitates the exhumation. We document the effect of slab retreat on the shape of P-T paths using the example of the Phyllite-Quartzite Nappe that has been exhumed below the Cretan syn-orogenic detachment during the Miocene in Crete and the Peloponnese. Data show a clear tendency toward colder conditions at peak pressure and during exhumation where the intensity of slab retreat is larger. This spatial evolution of P-T gradient is accompanied with an evolution from a partly coaxial regime below the Peloponnese section of the detachment toward a clearly non-coaxial regime in Crete

Aerodynamics of aero-engine installation

This paper describes current progress in the development of methods to assess aero-engine airframe installation effects. The aerodynamic characteristics of isolated intakes, a typical transonic transport aircraft as well as a combination of a through-flow nacelle and aircraft configuration have been evaluated. The validation task for an isolated engine nacelle is carried out with concern for the accuracy in the assessment of intake performance descriptors such as mass flow capture ratio and drag rise Mach number. The necessary mesh and modelling requirements to simulate the nacelle aerodynamics are determined. Furthermore, the validation of the numerical model for the aircraft is performed as an extension of work that has been carried out under previous drag prediction research programmes. The validation of the aircraft model has been extended to include the geometry with through flow nacelles. Finally, the assessment of the mutual impact of the through flow nacelle and aircraft aerodynamics was performed. The drag and lift coefficient breakdown has been presented in order to identify the component sources of the drag associated with the engine installation. The paper concludes with an assessment of installation drag for through-flow nacelles and the determination of aerodynamic interference between the nacelle and the aircraft

Three-dimensional structural characterization of centrosomes from early Drosophila embryos.

An understanding of the mechanism and structure of microtubule (MT)-nucleating sites within the pericentriolar material (PCM) of the centrosome has been elusive. This is partly due to the difficulty in obtaining large quantities of centrosomes for analysis, as well as to the problem of attaining interpretable structural data with conventional EM techniques. We describe a protocol for isolating a large quantity of functional centrosomes from early Drosophila embryos. Using automated electron tomography, we have begun a three-dimensional structural characterization of these intact centrosomes with and without regrown MTs. Reconstructions of the centrosomes to approximately 6-8 nm resolution revealed no large structures at the minus ends of MTs, suggesting that if MT-nucleating material physically contacts the MTs, it must conform closely to the shape of the minus end. While many MTs originate near the centrioles, MT minus ends were found throughout the PCM, and even close to its outer boundary. The MTs criss-crossed the PCM, suggesting that nucleating sites are oriented in many different directions. Reconstructions of centrosomes without MTs suggest that there is a reorganization of the PCM upon MT regrowth; moreover, ring-like structures that have a similar diameter as MTs are apparent in the PCM of centrosomes without MTs, and may be MT-nucleating sites

Climate change 2014 : impacts, adaptation, and vulnerability

Current and future climate-related drivers of risk for small islands during the 21st century include sea level rise (SLR), tropical and extratropical cyclones, increasing air and sea surface temperatures, and changing rainfall patterns (high confidence; robust evidence, high agreement). Current impacts associated with these changes confirm findings reported on small islands from the Fourth Assessment Report (AR4) and previous IPCC assessments. The future risks associated with these drivers include loss of adaptive capacity and ecosystem services critical to lives and livelihoods in small islands.peer-reviewe

Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries

A method of in situ hybridization for visualizing individual human chromosomes from pter to qter, both in metaphase spreads and interphase nuclei, is reported. DNA inserts from a single chromosomal library are labeled with biotin and partially preannealed with a titrated amount of total human genomic DNA prior to hybridization with cellular or chromosomal preparations. The cross-hybridization of repetitive sequences to nontargeted chromosomes can be markedly suppressed under appropriate preannealing conditions. The remaining single-stranded DNA is hybridized to specimens of interest and detected with fluorescent or enzymelabeled avidin conjugates following post-hybridization washes. DNA inserts from recombinant libraries for chromosomes 1, 4, 7, 8, 13, 14, 18, 20, 21, 22, and X were assessed for their ability to decorate specifically their cognate chromosome; most libraries proved to be highly specific. Quantitative densitometric analyses indicated that the ratio of specific to nonspecific hybridization signal under optimal preannealing conditions was at least 8:1. Interphase nuclei showed a cohesive territorial organization of chromosomal domains, and laserscanning confocal fluorescence microscopy was used to aid the 3-D visualization of these domains. This method should be useful for both karyotypic studies and for the analysis of chromosome topography in interphase cells

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

Quaternary geology of the Northern Great Plains

The Great Plains physiographic province lies east of the Rocky Mountains and extends from southern Alberta and Saskatchewan nearly to the United States-Mexico border. This chapter covers only the northern part of the unglaciated portion of this huge region, from Oklahoma almost to the United StatesCanada border, a portion that herein will be referred to simply as the Northern Great Plains (Fig. 1). This region is in the rain shadow of the Rocky Mountains. Isoheyets are roughly longitudinal, and mean annual precipitation decreases from about 750 mm at the southeastern margin to less than 380 mm in the western and northern parts (Fig. 2). Winters typically are cold with relatively little precipitation, mostly as snow; summers are hot with increased precipitation, chiefly associated with movement of Pacific and Arctic air masses into warm, humid air masses from the Gulf of Mexico. Vegetation is almost wholly prairie grassland, due to the semiarid, markedly seasonal climate. The Northern Great Plains is a large region of generally low relief sloping eastward from the Rocky Mountains toward the Missouri and Mississippi Rivers. Its basic bedrock structure is a broad syncline, punctuated by the Black Hills and a few smaller uplifts, and by structural basins such as the Williston, Powder River, and Denver-Julesburg Basins (Fig. 3). Its surface bedrock is chiefly Cretaceous and Tertiary sediments, with small areas of older rocks in the Black Hills, central Montana, and eastern parts of Wyoming, Kansas, and Oklahoma. During the Laramide orogeny (latest Cretaceous through Eocene), while the Rocky Mountains and Black Hills were rising, synorogenic sediments (frequently with large amounts of volcanic ash from volcanic centers in the Rocky Mountains) were deposited in the subsiding Denver-Julesburg, Powder River, and other basins. From Oligocene to Miocene time, sedimentation generally slowed with declining tectonism and volcanism in the Rocky Mountains. However, since the later Miocene, epeirogenic uplift, probably associated with the East Pacific Rise, affected the Great Plains and particularly the Rocky Mountains. During the last 10 m.y. the Rocky Mountain front has risen 1.5 to 2 km, and the eastern margin of the Great Plains 100 to 500 m (Gable and Hatton, 1983), with half to one-quarter of these amounts during the last 5 m.y. Thus, during the later Miocene the Great Plains became a huge aggrading piedmont sloping gently eastward from the Rocky Mountains and Black Hills, with generally eastward drainage, on which the Ogallala Formation and equivalents was deposited. The Ogallala underlies the High Plains Surface, the highest and oldest geomorphic surface preserved in this region. It has been completely eroded along some parts of the western margin of the region (e.g., the Colorado Piedmont), but eastward, it (and its equivalents, such as the Flaxville gravels in Montana) locally is preserved as caprock or buried by Quaternary sediments (Alden, 1924, 1932; Howard, 1960; Stanley, 1971, 1976; Pearl, 1971; Scott, 1982; Corner and Diffendal, 1983; Diffendal and Corner, 1984; Swinehart and others, 1985; Aber, 1985). During the Pliocene, regional aggradation slowly changed to dissection by the principal rivers. In the western part of the region the rivers flowed eastward, but the continental drainage divide Figure 3. Major bedrock structures of the Northern Great Plains. extended northeast from the Black Hills through central South Dakota, far south of its present position. The ancestral upper Missouri, Little Missouri, Yellowstone, and Cheyenne Rivers drained northeast to Hudson Bay, whereas the ancestral White, Platte, and Arkansas Rivers went to the Gulf of Mexico (Fig 4A). Their courses are marked by scattered surface and subsurface gravel remnants; in Montana and North Dakota, deposits of the preglacial Missouri River and its tributaries are buried deeply beneath glacial and other sediments (Howard, 1960; Bluemle, 1972)