Inactive Regions Research Articles

Mixing characteristics of sludge simulant in a model anaerobic digester.

This study aims to investigate the mixing characteristics of a transparent sludge simulant in a mechanically agitated model digester using flow visualisation technique. Video images of the flow patterns were obtained by recording the progress of an acid-base reaction and analysed to determine the active and inactive volumes as a function of time. The doughnut-shaped inactive region formed above and below the impeller in low concentration simulant decreases in size with time and disappears finally. The 'cavern' shaped active mixing region formed around the impeller in simulant solutions with higher concentrations increases with increasing agitation time and reaches a steady state equilibrium size, which is a function of specific power input. These results indicate that the active volume is jointly determined by simulant rheology and specific power input. A mathematical correlation is proposed to estimate the active volume as a function of simulant concentration in terms of yield Reynolds number.

Using Markov chains of nucleotide sequences as a possible precursor to predict functional roles of human genome: a case study on inactive chromatin regions.

Recent advances in computational epigenetics have provided new opportunities to evaluate n-gram probabilistic language models. In this paper, we describe a systematic genome-wide approach for predicting functional roles in inactive chromatin regions by using a sequence-based Markovian chromatin map of the human genome. We demonstrate that Markov chains of sequences can be used as a precursor to predict functional roles in heterochromatin regions and provide an example comparing two publicly available chromatin annotations of large-scale epigenomics projects: ENCODE project consortium and Roadmap Epigenomics consortium.

Time and State Dependence in an Ss Decision Experiment

Flow earnings in a laboratory experiment decline the further a Brownian state variable, z, evolves from its optimal level, z *. Optimal state dependent models predict subjects will pay a fixed cost to return z to z * only when z strays outside a critical inaction region around the optimum. On average, subjects adjust at states remarkably close to optimal threshold levels but, as in the field, do not establish true “state dependent” inaction regions, suggesting significant “time dependent” components in adjustment rules. Structural estimates of subjective observation cost qualitatively account for variation in time dependence observed across treatments. (JEL C91, D21, D80)

Spatial pattern and its evolution of Chinese provincial population: Methods and empirical study

China has been experiencing an unprecedented urbanization process. In 2011, China’s urban population reached 691 million with an urbanization rate of 51.27%. Urbanization level is expected to increase to 70% in China in 2030, reflecting the projection that nearly 300 million people would migrate from rural areas to urban areas over this period. At the same time, the total fertility rate of China’s population is declining due to the combined effect of economic growth, environmental carrying capacity, and modern social consciousness. The Chinese government has loosened its “one-child policy” gradually by allowing childbearing couples to have the second child as long as either of them is from a one-child family. In such rapidly developing country, the natural growth and spatial migration will consistently reshape spatial pattern of population. An accurate prediction of the future spatial pattern of population and its evolution trend are critical to key policy-making processes and spatial planning in China including urbanization, land use development, ecological conservation and environmental protection. In this paper, a top-down method is developed to project the spatial distribution of China’s future population with considerations of both natural population growth at provincial level and the provincial migration from 2010 to 2050. Building on this, the spatial pattern and evolution trend of Chinese provincial population are analyzed. The results suggested that the overall spatial pattern of Chinese population will be unlikely changed in next four decades, with the east area having the highest population density and followed by central area, northeast and west area. Four provinces in the east, Shanghai, Beijing, Tianjin and Jiangsu, will remain the top in terms of population density in China, and Xinjiang, Qinghai and Tibet will continue to have the lowest density of population. We introduced an index system to classify the Chinese provinces into three categories in terms of provincial population densities: Fast Changing Populated Region (FCPR), Low Changing Populated Region (LCPR) and Inactive Populated Region (IPR). In the FCPR, China’s population is projected to continue to concentrate in net immigration leading type (NILT) area where receives nearly 99% of new accumulated floating population. Population densities of Shanghai, Beijing, Zhejiang will peak in 2030, while the population density in Guangdong will keep increasing until 2035. Net emigration leading type (NELT) area will account for 75% of emigration population, including Henan, Anhui, Chongqing and Hubei. Natural growth will play a dominant role in natural growth leading type area, such as Liaoning and Shandong, because there will be few emigration population. Due to the large amount of moving-out labors and gradually declining fertility rates, population density of the LCPR region exhibits a downward trend, except for Fujian and Hainan. The majority of the western provinces will be likely to remain relatively low population density, with an average value of no more than 100 persons per km2.

Elimination of Spurious Modes in SH0 Lithium Niobate Laterally Vibrating Resonators

This letter reports on a spurious mode suppression technique for the shear horizontal (SH0) mode lithium niobate laterally vibrating resonators. The concept utilizes triangular and arched edge shapes on the transversal sides of a resonant cavity to effectively distribute and scatter the acoustic waves in the inactive regions, yielding the suppression of transverse spurious modes. 2D models and 3D finite-element analyses were employed to theoretically verify the technique. For devices with the arched-shape edges, complete removal of higher order transverse modes has been experimentally demonstrated with $2\times $ enhancement for quality factor ( $Q$ ). The $Q$ enhancement arises from the improved concentration of mechanical energy under the inter-digitated transducers. The fabricated device exhibits a $Q$ of 920, a large electromechanical coupling ( $k_{t}^{2}$ ) of 17.8%, and a figure of merit of 164.

Quality Factor Dependence on the Inactive Regions in AlN Contour-Mode Resonators

This paper investigates the dependence of the quality factor $({Q})$ of AlN contour mode resonators (CMRs) on the characteristics of the inactive regions located between the main resonator body (active region) and the stress-free surfaces placed beside the anchors. This paper shows that it is possible to reduce the energy leakage through the anchors by optimally sizing the width of such regions. To validate this concept, we built 16 different configurations of 225-MHz AlN CMRs, differing just by the size of the resonator inactive regions.

Donkey genome and insight into the imprinting of fast karyotype evolution.

The donkey, like the horse, is a promising model for exploring karyotypic instability. We report the de novo whole-genome assemblies of the donkey and the Asiatic wild ass. Our results reflect the distinct characteristics of donkeys, including more effective energy metabolism and better immunity than horses. The donkey shows a steady demographic trajectory. We detected abundant satellite sequences in some inactive centromere regions but not in neocentromere regions, while ribosomal RNAs frequently emerged in neocentromere regions but not in the obsolete centromere regions. Expanded miRNA families and five newly discovered miRNA target genes involved in meiosis may be associated with fast karyotype evolution. APC/C, controlling sister chromatid segregation, cytokinesis, and the establishment of the G1 cell cycle phase were identified by analysis of miRNA targets and rapidly evolving genes.

Nucleosome Organization in Human Embryonic Stem Cells.

The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a “ground state” of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this “ground state” by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states) are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational analysis of nucleosome organization alone is sufficient to elucidate much of the circuitry of pluripotency. Our results, suggest that nucleosome organization is associated with numerous genomic and epigenomic processes and can be used to elucidate cellular identity.

An Overview of Inside-Out Planet Formation

AbstractThe Kepler-discovered Systems with Tightly-packed Inner Planets (STIPs), typically with several planets of Earth to super-Earth masses on well-aligned, sub-AU orbits may host the most common type of planets, including habitable planets, in the Galaxy. They pose a great challenge for planet formation theories, which fall into two broad classes: (1) formation further out followed by inward migration; (2) formation in situ, in the very inner regions of the protoplanetary disk. We review the pros and cons of these classes, before focusing on a new theory of sequential in situ formation from the inside-out via creation of successive gravitationally unstable rings fed from a continuous stream of small (~cm-m size) “pebbles,” drifting inward via gas drag. Pebbles first collect at the pressure trap associated with the transition from a magnetorotational instability (MRI)-inactive (“dead zone”) region to an inner, MRI-active zone. A pebble ring builds up that begins to dominate the local mass surface density of the disk and spawns a planet. The planet continues to grow, most likely by pebble accretion, until it becomes massive enough to isolate itself from the accretion flow via gap opening. This reduces the local gas density near the planet, leading to enhanced ionization and a retreat of the dead zone inner boundary. The process repeats with a new pebble ring gathering at the new pressure maximum associated with this boundary. We discuss the theory's predictions for planetary masses, relative mass scalings with orbital radius, and minimum orbital separations, and their comparison with observed systems. Finally, we discuss open questions, including potential causes of diversity of planetary system architectures, i.e., STIPs versus Solar System analogs.

Global SUMOylation on active chromatin is an acute heat stress response restricting transcription.

BackgroundCells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription.ResultsWe mapped HS-induced genome-wide changes in chromatin occupancy of SUMO-2/3-modified proteins in K562 and VCaP cells using ChIP-seq. Chromatin SUMOylation was further correlated with HS-induced global changes in transcription using GRO-seq and RNA polymerase II (Pol2) ChIP-seq along with ENCODE data for K562 cells. HS induced a rapid and massive rearrangement of chromatin SUMOylation pattern: SUMOylation was gained at active promoters and enhancers associated with multiple transcription factors, including heat shock factor 1. Concomitant loss of SUMOylation occurred at inactive intergenic chromatin regions that were associated with CTCF-cohesin complex and SETDB1 methyltransferase complex. In addition, HS triggered a dynamic chromatin binding of SUMO ligase PIAS1, especially onto promoters. The HS-induced SUMOylation on chromatin was most notable at promoters of transcribed genes where it positively correlated with active transcription and Pol2 promoter-proximal pausing. Furthermore, silencing of SUMOylation machinery either by depletion of UBC9 or PIAS1 enhanced expression of HS-induced genes.ConclusionsHS-triggered SUMOylation targets promoters and enhancers of actively transcribed genes where it restricts the transcriptional activity of the HS-induced genes. PIAS1-mediated promoter SUMOylation is likely to regulate Pol2-associated factors in HS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0717-y) contains supplementary material, which is available to authorized users.

Relating Anode Gaps to the Positioning of the Reference Electrode in PEM Fuel Cells

We present analytical solutions for the potential and current density distributions in the vicinity of inactive (“dead”) regions inside a PEM fuel cell anode. For simplicity, the dead region is modeled as a step function for the anode exchange current density, representing membrane gaps or delamination. The solutions exhibit a large peak of the anode current density just outside the dead region. This overshoot can substantially exceed the average current density, thereby accelerating membrane degradation. In the limit of large gap sizes, we demonstrate how these findings relate to the positioning of a reference electrode which can independently measure the anode and cathode overpotential, respectively. [1] A. A. Kulikovsky and P. Berg, Analytical description of a dead spot in a PEM fuel cell anode, ECS Electrochem. Lett., 2, pp. F64-F67 (2013) [2] P. Berg and A. A. Kulikovsky, A model for a crack or a delaminated region in a PEM fuel cell anode: Analytical solutions, Electrochim. Acta, submitted.

INDUCED SEISMICITY. High-rate injection is associated with the increase in U.S. mid-continent seismicity.

An unprecedented increase in earthquakes in the U.S. mid-continent began in 2009. Many of these earthquakes have been documented as induced by wastewater injection. We examine the relationship between wastewater injection and U.S. mid-continent seismicity using a newly assembled injection well database for the central and eastern United States. We find that the entire increase in earthquake rate is associated with fluid injection wells. High-rate injection wells (>300,000 barrels per month) are much more likely to be associated with earthquakes than lower-rate wells. At the scale of our study, a well's cumulative injected volume, monthly wellhead pressure, depth, and proximity to crystalline basement do not strongly correlate with earthquake association. Managing injection rates may be a useful tool to minimize the likelihood of induced earthquakes.

Making quakes depends on injection rates

Induced Seismicity Wastewater injection wells induce earthquakes that garner much attention, especially in tectonically inactive regions. Weingarten et al. combined information from public injection-well databases from the eastern and central United States with the best earthquake catalog available

The Proportion of Chromatin Graded between Closed and Open States Determines the Level of Transcripts Derived from Distinct Promoters in the CYP19 Gene.

The human CYP19 gene encodes aromatase, which converts androgens to estrogens. CYP19 mRNA variants are transcribed mainly from three promoters. Quantitative RT-PCR was used to measure the relative amounts of each of the three transcripts and determine the on/off state of the promoters. While some of the promoters were silent, CYP19 mRNA production differed among the other promoters, whose estimated transcription levels were 0.001% to 0.1% of that of the TUBB control gene. To investigate the structural aspects of chromatin that were responsible for this wide range of activity of the CYP19 promoters, we used a fractionation protocol, designated SEVENS, which sequentially separates densely packed nucleosomes from dispersed nucleosomes. The fractional distribution of each inactive promoter showed a similar pattern to that of the repressed reference loci; the inactive regions were distributed toward lower fractions, in which closed chromatin comprising packed nucleosomes was enriched. In contrast, active CYP19 promoters were raised toward upper fractions, including dispersed nucleosomes in open chromatin. Importantly, these active promoters were moderately enriched in the upper fractions as compared to active reference loci, such as the TUBB promoter; the proportion of open chromatin appeared to be positively correlated to the promoter strength. These results, together with ectopic transcription accompanied by an increase in the proportion of open chromatin in cells treated with an H3K27me inhibitor, indicate that CYP19 mRNA could be transcribed from a promoter in which chromatin is shifted toward an open state in the equilibrium between closed and open chromatin.

Nuclear matrix revisited?

Nuclear matrix revisited?

Characterization and dynamics of pericentromere-associated domains in mice.

Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellite repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin, and aggregate into nuclear chromocenters. These nuclear landmark structures are assumed to form a repressive compartment in the nucleus to which genes are recruited for silencing. We have designed a strategy for genome-wide identification of pericentromere-associated domains (PADs) in different mouse cell types. The ∼1000 PADs and non-PADs have similar chromatin states in embryonic stem cells, but during lineage commitment, chromocenters progressively associate with constitutively inactive genomic regions at the nuclear periphery. This suggests that PADs are not actively recruited to chromocenters, but that chromocenters are themselves attracted to inactive chromatin compartments. However, we also found that experimentally induced proximity of an active locus to chromocenters was sufficient to cause gene repression. Collectively, our data suggest that rather than driving nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions into nuclear compartments where they can contribute to stable maintenance of the repressed status of proximal chromosomal regions.

Highly Efficient and Adaptive Numerical Scheme to Analyze Multipactor in Waveguide Devices

A novel numerical scheme is proposed in the hybrid numerical method, combining the conformal time-domain finite integral theorem with the particle-in-cell method, to analyze the multipactor in waveguide devices more efficiently. In multipactor analysis, the electromagnetic waves and charged particles interact only in the interior regions of waveguide devices. Hence, elements outside the waveguide device are valueless in multipactor simulations. To improve the efficiency in simulations, we propose an efficient numerical scheme to accurately eliminate the inactive regions. Meanwhile, an adaptive hybrid container is presented to perfectly implement our simple but highly efficient scheme. From two practical examples, it is validated that the memory requirement and runtime can be significantly saved by the proposed method.

Two State Stochastic Control Models with Fix Costs

In this document I analyze a stochastic control model with a two dimensional state variable and fix costs. To illustrate the results, I study a simple Central Bank decision model with multiple objectives and restricted number of policy instruments in which in absence of intervention, objective variables follow diffusion processes. I present the solution to a baseline model in which both state variables can be controlled separately and compared them to the case in which there is only one control variable to change both states. I solve the models numerically and suggest a characterization of the respective inaction and control regions.

A Nonconvex Singular Stochastic Control Problem and its Related Optimal Stopping Boundaries

Equivalences are known between problems of singular stochastic control (SSC) with convex performance criteria and related questions of optimal stopping; see, for example, Karatzas and Shreve [SIAM J. Control Optim., 22 (1984), pp. 856--877]. The aim of this paper is to investigate how far connections of this type generalize to a nonconvex problem of purchasing electricity. Where the classical equivalence breaks down we provide alternative connections to optimal stopping problems. We consider a nonconvex infinite time horizon SSC problem whose state consists of an uncontrolled diffusion representing a real-valued commodity price, and a controlled increasing bounded process representing an inventory. We analyze the geometry of the action and inaction regions by characterizing their (optimal) boundaries. Unlike the case of convex SSC problems we find that the optimal boundaries may be both reflecting and repelling and it is natural to interpret the problem as one of SSC with discretionary stopping.

Normal RUNX1 and Pathogenic ETV6/RUNX1 Compete Genome-Wide for Chromatin Binding in Pre-B Acute Lymphoblastic Leukemia

Introduction and objectives:The ETV6/RUNX1 fusion protein is a leukemia-initiating transcription factor that interferes with normal RUNX1 transcription factor function. Although RUNX1 can be either a repressor or an activator, ETV6/RUNX1 is mainly associated with transcriptional repression. Both RUNX1 and ETV6/RUNX1 proteins are expressed in pre-B acute lymphoblasts and bind the same DNA binding motif, which is normally recognized by the RUNX1 DNA binding domain, therefore competing for gene regulation with possible adverse transcriptional effects. Here, (we address the question of how) do the abnormal transcription factor ETV6/RUNX1 and the normal RUNX1 interplay at the chromatin level to modulate expression of genes, possibly giving rise to leukemia.Materials and methods:We used chromatin-immunoprecipitation coupled with sequencing (ChIP-seq) both in pre-B leukemic REH cells, which originate from a relapse of an ETV6/RUNX1 leukemic patient and lack the non-translocated allele of ETV6, and in pre-B leukemic Nalm6 cells that are ETV6/RUNX1-negative, to characterize the genomic distribution of ETV6/RUNX1 and RUNX1, as well as transcriptionnally active and inactive chromatin regions (ChIP-seq for methylated H3K4me3 and H3K4me1 histones, and acetylated H3K27achistones). In addition, we ran microarrays experiments to define the transcriptional programme associated with ETV6/RUNX1 and RUNX1 expression in pre-B cell lines. Data were compared to gene expression data from ETV6/RUNX1 pre-B acute lymphoblastic leukemia samples.Results:Through mapping the genome-wide distribution of RUNX1 et ETV6/RUNX1, we identified both common and exclusive DNA sites. We further characterized the DNA binding motifs of RUNX1 and ETV6/RUNX1, which were particularly enriched within particular transposon sequences. ChIP-seq of histone marks identified active and inactive chromatin in correlation with ETV6/RUNX1- and RUNX1-binding. Direct target genes for both transcription factors were defined and used for gene ontology analysis, allowing to uncover specific biological functions associated with ETV6/RUNX1 and RUNX1 binding events. Finally, we show that a fraction of the genes misregulated in pre-B acute lymphoblastic leukemia patients are directly controlled by ETV6/RUNX1 and RUNX1.Conclusion:Our data give new insights on the competition between the fusion protein ETV6/RUNX1 and normal RUNX1 in pre-B acute lymphoblastic leukemia at chromatin level genome-wide.This work was supported by CNRS, University of Rennes 1, University Hospital of Rennes, Ligue Régionale contre le Cancer (sections 22, 35 and 56) (MPA, VG, MBT), Région Bretagne (MBT, VG), Rennes Métropole (MBT), SFR Biosit UMS 3480 (VG, MBT), Société Française de Lutte contre les Cancers et les Leucémies de l’Enfant et de l’Adolescent and the Fédération Enfants et Santé (MBT), Association Laurette Fugain (VG) and the People Programme (Marie Curie Actions) of the European Union Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n°291851 (MBT). DisclosuresNo relevant conflicts of interest to declare.