Weak Island Research Articles

Different measures of “genome-wide” DNA methylation exhibit unique properties in placental and somatic tissues

DNA methylation of CpGs located in two types of repetitive elements—LINE1 (L1) and Alu—is used to assess “global” changes in DNA methylation in studies of human disease and environmental exposure. L1 and Alu contribute close to 30% of all base pairs in the human genome and transposition of repetitive elements is repressed through DNA methylation. Few studies have investigated whether repetitive element DNA methylation is associated with DNA methylation at other genomic regions, or the biological and technical factors that influence potential associations. Here, we assess L1 and Alu DNA methylation by Pyrosequencing of consensus sequences and using subsets of probes included in the Illumina Infinium HumanMethylation27 BeadChip array. We show that evolutionary age and assay method affect the assessment of repetitive element DNA methylation. Additionally, we compare Pyrosequencing results for repetitive elements to average DNA methylation of CpG islands, as assessed by array probes classified into strong, weak and non-islands. We demonstrate that each of these dispersed sequences exhibits different patterns of tissue-specific DNA methylation. Correlation of DNA methylation suggests an association between L1 and weak CpG island DNA methylation in some of the tissues examined. We caution, however, that L1, Alu and CpG island DNA methylation are distinct measures of dispersed DNA methylation and one should not be used in lieu of another. Analysis of DNA methylation data is complex and assays may be influenced by environment and pathology in different or complementary ways.

Allele-Specific, Age-Dependent and BMI-Associated DNA Methylation of Human MCHR1

BackgroundMelanin-concentrating hormone receptor 1 (MCHR1) plays a significant role in regulation of energy balance, food intake, physical activity and body weight in humans and rodents. Several association studies for human obesity showed contrary results concerning the SNPs rs133072 (G/A) and rs133073 (T/C), which localize to the first exon of MCHR1. The variations constitute two main haplotypes (GT, AC). Both SNPs affect CpG dinucleotides, whereby each haplotype contains a potential methylation site at one of the two SNP positions. In addition, 15 CpGs in close vicinity of these SNPs constitute a weak CpG island. Here, we studied whether DNA methylation in this sequence context may contribute to population- and age-specific effects of MCHR1 alleles in obesity.Principal FindingsWe analyzed DNA methylation of a 315 bp region of MCHR1 encompassing rs133072 and rs133073 and the CpG island in blood samples of 49 individuals by bisulfite sequencing. The AC haplotype shows a significantly higher methylation level than the GT haplotype. This allele-specific methylation is age-dependent. In young individuals (20–30 years) the difference in DNA methylation between haplotypes is significant; whereas in individuals older than 60 years it is not detectable. Interestingly, the GT allele shows a decrease in methylation status with increasing BMI, whereas the methylation of the AC allele is not associated with this phenotype. Heterozygous lymphoblastoid cell lines show the same pattern of allele-specific DNA methylation. The cell line, which exhibits the highest difference in methylation levels between both haplotypes, also shows allele-specific transcription of MCHR1, which can be abolished by treatment with the DNA methylase inhibitor 5-aza-2′-deoxycytidine.ConclusionsWe show that DNA methylation at MCHR1 is allele-specific, age-dependent, BMI-associated and affects transcription. Conceivably, this epigenetic regulation contributes to the age- and/or population specific effects reported for MCHR1 in several human obesity studies.

A structural asymmetry in intervention effects

This paper documents a previously unnoted structural asymmetry among wh-phrases with respect to intervention effects. I show in a series of experiments (phonetic and syntactic) that in Korean (and potentially in Japanese and Turkish), only wh-phrases that are base generated in a structurally low position trigger intervention effects while wh-phrases generated in a high position do not. I show that these structural positions do not align with expectations from work on weak island effects: it is the syntactic position, not the semantic type, of the wh-phrase that matters. This result supports an important insight that the sensitivity to IEs does not necessarily depend on the argument-adjunct difference ( Rizzi, 1992; Miyagawa, 2002). I further show how these empirical contrasts are accounted for along the lines of the earlier work on intervention effects, which made use of structural constraints stated over LF representations.

Modeling and Control of VSC-HVDC Links Connected to Island Systems

The recently proposed power-synchronization control for grid-connected voltage-source converters (VSCs) has been shown to be a feasible solution for high-voltage direct-current (HVDC) transmission connected to high-impedance weak ac systems. In this paper, power-synchronization control is investigated for VSC-HVDC links connected to another type of weak ac system, i.e., low-inertia or island systems. As an example, a linear model of a typical island system feeding by a VSC-HVDC link, including a synchronous generator, an induction motor, and some passive loads, is developed for tuning the control parameters of the VSC-HVDC link. Time simulations in PSCAD/EMTDC demonstrate that VSC-HVDC systems using power-synchronization control are flexible for various network conditions, such as large-ac-system connection, island systems, or passive networks. The time simulations also show that power-synchronization control can seamlessly handle transitions between operation modes, as well as ride through ac-system faults in all network conditions.

Interplay between DNA Methylation and Transcription Factor Availability: Implications for Developmental Activation of the Mouse Myogenin Gene

During development, gene activation is stringently regulated to restrict expression only to the correct cell type and correct developmental stage. Here, we present mechanistic evidence that suggests DNA methylation contributes to this regulation by suppressing premature gene activation. Using the mouse Myogenin promoter as an example of the weak CpG island class of promoters, we find that it is initially methylated but becomes demethylated as development proceeds. Full hypersensitive site formation of the Myogenin promoter requires both the MEF2 and SIX binding sites, but binding to only one site can trigger the partial chromatin opening of the nonmethylated promoter. DNA methylation markedly decreases hypersensitive site formation that now occurs at a detectable level only when binding to both MEF2 and SIX binding sites is possible. This suggests that the probability of activating the methylated promoter is low until two of the factors are coexpressed within the same cell. Consistent with this, the single-cell analysis of developing somites shows that the coexpression of MEF2A and SIX1, which bind the MEF2 and SIX sites, correlates with the fraction of cells that demethylate the Myogenin promoter. Taken together, these studies imply that DNA methylation helps to prevent inappropriate gene activation until sufficient activating factors are coexpressed.

An argument for VP coordination: scene-setting coordination and weak islands

This article provides a minimalist analysis of a novel type of weak island that has not been discussed in the literature until now. The island is a subtype of extraction from asymmetric coordination islands in violation of the across-the-board constraint. The islands in question are characterised by being weak islands for certain types of adjunct extraction, and by being discontinuous – XP coordination. This article demonstrates the properties of this curious construction type and proposes the first analysis to date. It is argued that this is an instance of VP coordination and that this configuration allows the possibility of high merger of direct objects in a constrained fashion.

Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome

To gain insight into the function of DNA methylation at cis-regulatory regions and its impact on gene expression, we measured methylation, RNA polymerase occupancy and histone modifications at 16,000 promoters in primary human somatic and germline cells. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes are methylated in somatic cells, suggesting additional functional selection. These results show that promoter sequence and gene function are major predictors of promoter methylation states. Moreover, we observe that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.

Multiple generations of forearc mafic–ultramafic rocks in the Timor–Tanimbar ophiolite, eastern Indonesia

We investigated mafic–ultramafic rocks distributed in the Timor–Tanimbar region as a possible modern analogue for the Mediterranean-type ophiolites in the Tethyan system. The geological occurrence suggests that the buoyant subduction of Australian continent uplifted the fragments of newly formed mantle–crust section, which extends to the neighboring preemplaced forearc marginal basins. However, we recognized a large variety of igneous features, which is consistent with the lack of complete succession and the presence of abundant crosscutting structures. All peridotite masses in Timor (Mutis, Atapupu and Dili) are mostly fertile (lherzolitic) in compositions. In addition, we found depleted harzburgite, highly refractory dunite and olivine websterite to occur as minor constituents, which display compositional contrast to those of the lherzolites. Structurally overlying Ocussi volcanics resemble island–arc tholeiite in terms of trace element characteristics, apparently inconsistent with genetic relationship with Timor lherzolite masses. In eastern small islands (Moa and Dai), all types of ophiolitic rocks display varying degrees of island–arc affinities. Cumulate origin of wehrlite and gabbroic rocks in Dai is marked by early crystallization of clinopyroxene and common occurrence of high-calcic plagioclase. Dikes cutting the gabbro sequence have weak island–arc signatures relative to those of Ocussi volcanics. Mildly depleted lherzolite–harzburgite in Moa was intruded by high-Mg andesitic magma, which crystallized hornblende gabbro containing high-Mg orthopyroxene. These petrological and geochemical variations can be best explained by the combination of (1) a temporal change of igneous activity possibly associated with development of forearc basin and (2) the emplacement of spatially different forearc regions in each locality. Unusual occurrence of fertile lherzolite in the forearc setting, generation of high-Mg andesite magmatism, inverted metamorphic grade recorded from associated metamorphic rocks, and formation of marginal basins may be linked to the injection of high-temperature asthenospheric materials into the mantle wedge.

Analysis of state of MV distribution system before and after connection of small wind farm Ravna1

In the last two decades, the number of installed wind turbines has grown rapidly all over the world. This was due to the huge improvement in technology and increased interest in using wind energy as an important energy source in the future. Following this worldwide trend, the first small wind farm in Croatia named Ravna1 was installed on the Pag Island. To check its influence on local distribution network, power quality measurements have been made in different points in the network before and after the connection of the small wind farm. In parallel, simulation of the distribution network with its connection to 110 kV network was made, and power flow and voltage analysis were made for cases of network with and without wind farm connected. Analyses were made to check the influence of the connection of the wind park on the relatively weak island network, and were made with different power outputs of wind turbines. Calculated values of power flows and values of voltages in the network match very well with measured ones. Also, measurements show that connection of small wind farm does not affect power quality on the Pag Island distribution network.

Evidence for methylation‐dependent epigenetic silencing of a weak CpG island‐containing gene, C8orf4, in human breast cancer cells

C8orf4 is a TGFb-inducible gene that is expressed in normal colonic epithelium, but lost in many primary colon cancers. Gene expression analysis showed low levels or lack of C8orf4 expression in 12/12 (100%) breast cancer cell lines examined. Treatment of MCF7 cells with 5aza or 5aza + TSA results in significant C8orf4 expression, suggesting that this gene is subject to methylation-dependent silencing in breast cancer cells. The promoter of C8orf4 lacks features expected for an epigenetically-regulated gene (CpG island), but does contain a small number of promoter CpG dinucleotides and a weak CpG island in exon 1. Bisulfite sequencing showed extensive methylation of CpG dinucleotides in the promoter and exon 1 of C8orf4 in MCF7, ZR-75-1, MDA-MB-453, BT-20, and SK-BR-3 cells, establishing a strong correlation between promoter/exon 1 methylation and expression status in these cell lines. Treatment of MCF7 cells with 5aza or 5aza + TSA resulted in demethylation of the promoter/exon 1 region, coordinate with expression of C8orf4. Withdrawal of treatment resulted in silencing of C8orf4 expression and remethylation of these CpG dinucleotides. These results suggest strongly that C8orf4 is epigenetically regulated despite the lack of typical features expected for methylation-sensitive genes (including typical CpG islands) and that this gene may be important in control of breast epithelial cell proliferation. Support: NIH CA78343, Komen Foundation BCTR0100575.

Evaluation of an Urban Canopy Parameterization in a Mesoscale Model Using VTMX and URBAN 2000 Data

Abstract A modified urban canopy parameterization (UCP) is developed and evaluated in a three-dimensional mesoscale model to assess the urban impact on surface and lower-atmospheric properties. This parameterization accounts for the effects of building drag, turbulent production, radiation balance, anthropogenic heating, and building rooftop heating/cooling. U.S. Geological Survey (USGS) land-use data are also utilized to derive urban infrastructure and urban surface properties needed for driving the UCP. An intensive observational period with clear sky, strong ambient wind, and drainage flow, and the absence of a land–lake breeze over the Salt Lake Valley, occurring on 25–26 October 2000, is selected for this study. A series of sensitivity experiments are performed to gain understanding of the urban impact in the mesoscale model. Results indicate that within the selected urban environment, urban surface characteristics and anthropogenic heating play little role in the formation of the modeled nocturnal urban boundary layer. The rooftop effect appears to be the main contributor to this urban boundary layer. Sensitivity experiments also show that for this weak urban heat island case, the model horizontal grid resolution is important in simulating the elevated inversion layer. The root-mean-square errors of the predicted wind and temperature with respect to surface station measurements exhibit substantially larger discrepancies at the urban locations than their rural counterparts. However, the close agreement of modeled tracer concentration with observations fairly justifies the modeled urban impact on the wind-direction shift and wind-drag effects.

Vegetation as an urban climate control in the subtropical city of Gaborone, Botswana

AbstractThe influence of vegetation on the urban climate was studied in the subtropical city Gaborone, the rapidly expanding capital of Botswana with approximately 200 000 inhabitants. Temperature records from an urban and a rural station were analysed for the period 1985–96. In an attempt to explain possible seasonal change in vegetation, NOAA satellite normalized difference vegetation index imagery was analysed. The present urban influence was investigated with temperature loggers at selected urban and rural sites. In addition, mobile measurements revealed spatial patterns in temperature and humidity for different land uses.Seasonal patterns of urban–rural differences in minimum temperatures emerge during the period 1994–96, especially during the winter when the heat island effect is largest. It is shown that differences in urban and rural vegetation over the year partly explain this variation. Mobile measurements reveal a weak nocturnal heat island of 2–3 °C during clear and calm nights. There are intra‐urban temperature differences that are in the same range as the urban–rural relationship due to the role of vegetation. Evapotranspiration lowers the temperature, which was detected by high humidity in areas of lush vegetation. This becomes apparent at midday, when densely vegetated areas were up to 2 °C cooler than rural sites. An oasis effect, therefore, only exists on a highly local basis. In contrast, parts of the city with sparse vegetation are warmer than the countryside.There is an apparent opposed effect of rural and urban vegetation, whereby the former is hindering the temperature from falling and the latter is cooling the environment through evapotranspiration. This can be explained by the overwhelming amounts of imported water in the city promoting evaporative cooling. Copyright © 2004 Royal Meteorological Society

Methylation of a CpG Island within the Uroplakin Ib Promoter: A Possible Mechanism for Loss of Uroplakin lb Expression in Bladder Carcinoma

Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs) but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1. This study examined the hypothesis that methylation of this CpG island regulates uroplakin Ib expression. Uroplakin Ib mRNA levels were determined by reverse transcription polymerase chain reaction and CpG methylation was assessed by bisulfite modification of DNA, PCR, and sequencing. A correlation was demonstrated in 15 TCC lines between uroplakin Ib mRNA expression and lack of CpG methylation. In support of a regulatory role for methylation, incubating uroplakin Ib-negative lines with 5-aza-2′ -deoxycytidine reactivated uroplakin Ib mRNA expression. A trend between uroplakin Ib mRNA expression and CpG methylation was also observed in normal urothelium and bladder carcinomas. In particular, loss of uroplakin Ib expression correlated with methylation of a putative Spi/NFκB binding motif. The data are consistent with the hypothesis that methylation of specific sites within the uroplakin Ib promoter may be an important factor in the loss of uroplakin Ib expression in TCCs.

Characteristics of the heat island effect in Shanghai and its possible mechanism

The characteristics of the urban heat island effect and the climate change in Shanghai and its possible mechanism are analyzed based on monthly meteorological data from 1961 to 1997 at 16 stations in Shanghai and its adjacent areas. The results indicate that Shanghai City has the characteristics of a heat island of air temperature and maximum and minimum air temperature, a cold island of surface soil temperature, a weak rainy island of precipitation, and a turbid island of minimum visibility and aerosols, with centers at or near Longhua station (the urban station of Shanghai). Besides theses, the characteristics of a cloudy island and sunshine duration island are also obvious, but their centers are located in the southern part of the urban area and in the southern suburbs. A linear trend analysis suggests that all of the above urban effects intensified from 1961 to 1997. So far as the heat island effect is concerned, the heat island index (difference of annual temperature between Longhua and Songjiang stations) strengthens (weakens) as the economic development increases (decreases). The authors suggest that the heating increase caused by increasing energy consumption due to economic development is a main factor in controlling the climate change of Shanghai besides natural factors. On the other hand, increasing pollution aerosols contribute to the enhancement of the turbid island and cooling. On the whole, the heating effect caused by increasing energy consumption is stronger than the cooling effect caused by the turbid island and pollution aerosols.

Toward a typology of focus and focus constructions

Departing from the assumption that focus is nonuniform (Drubig 1994; Kiss 1998) this paper takes preliminary steps toward a typology of focus and focus constructions. Focus is taken to be a syntactic feature assigned freely to word-level categories at numeration, licensed either by integration into a wider domain (presentational focus constructions) or by overt/covert movement to a functional projection headed by a polarity formative (focus operator constructions). Cross-linguistic variation in the target position of focus movement (sentence-peripheral vs. verb-adjacent) supports the stipulation of two polarity projections, one in COMP and one in INFL, with different effects on interpretation. A serious problem confronts the movement analysis of narrow focus in a number of languages that show striking parallels between focus and relative constructions (Schachter 1973): in some languages of this type sentence-peripheral foci bind resumptive pronouns without weak crossover or island effects. In this paper I propose a cleft analysis for this type of focus construction and discuss its typological implications.

Power conversion mechanisms for wave energy

It is easy to make a device that will respond vigorously to the action of sea waves. Indeed, it is quite hard to make one that will not. However, the conversion of the slow, random, reversing energy flows with very high extreme values into phase-locked synchronous electricity with power quality acceptable to a utility network is very much harder. This paper describes a range of different control strategies of varying degrees of sophistication and then describes possible conversion equipment for high-pressure oil and water and low-pressure air. Like many renewable energy sources, waves would benefit from some form of energy storage, particularly if they are to be used in weak island networks. Flywheels, gas accumulators, submerged oil/vacuum accumulators, thermal stores and reversible fuel cells are discussed, with emphasis on the coupling hardware. This leads on to a description of a new type of hydraulic machine with digital control which has been specially designed for high efficiency and flexible control of multiple erratic sources. An explanation of the rather low performance of air turbines in the random air flows caused by sea waves suggests the need for a variable-pitch version of the Wells turbine and the design of a reciprocating-flow wind-tunnel with recirculating energy recovery in which it could be tested.

Power conversion mechanisms for wave energy

It is easy to make a device that will respond vigorously to the action of sea waves. Indeed, it is quite hard to make one that will not. However, the conversion of the slow, random, reversing energy flows with very high extreme values into phase-locked synchronous electricity with power quality acceptable to a utility network is very much harder. This paper describes a range of different control strategies of varying degrees of sophistication and then describes possible conversion equipment for high-pressure oil and water and low-pressure air. Like many renewable energy sources, waves would benefit from some form of energy storage, particularly if they are to be used in weak island networks. Flywheels, gas accumulators, submerged oil/vacuum accumulators, thermal stores and reversible fuel cells are discussed, with emphasis on the coupling hardware. This leads on to a description of a new type of hydraulic machine with digital control which has been specially designed for high efficiency and flexible control of multiple erratic sources. An explanation of the rather low performance of air turbines in the random air flows caused by sea waves suggests the need for a variable-pitch version of the Wells turbine and the design of a reciprocating-flow wind-tunnel with recirculating energy recovery in which it could be tested.

Indefinites between Predication and Reference

No abstract.

Urban climatological studies in the Reykjavı́k subarctic environment, Iceland

The distribution of air temperature and wind speed was investigated in Reykjavı́k, the capital of Iceland, during the period from November 1991 to September 1992. The obtained data reveal that the climate in Reykjavı́k is mainly affected by the subarctic radiation budget, frequent cyclones penetrating into the investigation area and the closeness to the ocean. Nevertheless, Reykjavı́k shows a weak heat island effect, which converts to a `cold island’ by day in mid summer. The anthropogenic heat release amounts to ca. 35 W m −2. The study also indicates that the bioclimate and human comfort in Reykjavı́k is determined more by a high wind discomfort than by severe winter temperatures or high air pollution typical for high-latitude cities.

Chemical geodynamics in a back arc region around the Sea of Japan: Implications for the genesis of alkaline basalts in Japan, Korea, and China

Major and trace element have been analyzed from alkaline basalts from southwestern Japan, Korea, and northeastern China. No significant differences were found in the immobile incompatible element ratios, such as Zr, Y, Hf, Th, and Ti. These ratios, as well as normalized incompatible element patterns, resemble those of continental and oceanic island alkaline basalts. However, southwestern Japanese alkaline basalts show evidence of K, Ba, and Rb enrichment and a slight depletion in Ta relative to La, implying a weak island arc signature. Korean and Chinese alkaline basalts do not have such a signature. Rare earth elements (REE) show near‐constant La/Sm ratios and a crossover at the high REE end of patterns for each areas studied. The parallelism in light REE can be derived if the magmas are mixtures formed by (1) relatively large degrees of partial melting of an enriched mantle plume from deeper in the mantle and (2) a small degree of partial melting of a depleted mid‐ocean ridge basalt (MORB)‐type source. These observations when combined with seismic results suggest that the upper mantle beneath southwestern Japan has been weakly affected by metasomatism caused by dehydration and/or partial melting of subducted Pacific plate (not Philippine Sea plate). The mantle plume may have reacted with weakly metasomatized MORB‐type depleted mantle to produce alkaline basalt magmas retaining mild island arc characteristics in southwestern Japan. However, the metasomatism by the subduction of the Pacific plate has not affected the mantle beneath Korea and northeastern China. Here the interaction between plume and MORB‐type mantle produced alkaline basalt magma similar to normal continental and oceanic alkaline basalts.