Deficits in sound pattern sequencing in children with specific language impairment: A networks approach

Children with specific language impairment (SLI) demonstrate primary deficits in morphosyntax, which has served as the central theme in theoretical and clinical approaches. However, a striking number of children with SLI also exhibit speech sound deficits, characterized both by increased error patterns and by high levels of variability. These speech sound deficits have been under-studied and are not explicitly tied to accounts of SLI. In the present study, theoretical approaches drawn from dynamical systems and sequence learning are used to address speech production learning in children with SLI. Standard approaches to sound accuracy and variability and articulatory variability are integrated with novel applications of network science to assess sound learning trajectories over time. ^ The purpose of the present study was to examine how measures of accuracy and variability are related when assessing nonword production over three sessions. A networks approach is proposed that highlights quantitative and qualitative relationships of sound sequences. Results demonstrate that children with SLI are less accurate and more variable, yet there is a dissociation between these two indices. Examination of movement trajectories reveals that group differences in performance cannot be accounted for solely by articulatory ability. There is a strong correlation between segmental variability and the networks measures, and the information provided by this novel methodology demonstrates gaps in classic approaches to error analysis. Results suggest that children with SLI have difficulty with sound sequencing, and that network science may capture error patterns that classic approaches do not

Heat-evoked activation of TRPV4 channels in an HEK-293 cell expression system and in native mouse aorta endothelial cells

Peer reviewe

Susceptibility to Superhelically Driven DNA Duplex Destabilization: A Highly Conserved Property of Yeast Replication Origins

Strand separation is obligatory for several DNA functions, including replication. However, local DNA properties such as A+T content or thermodynamic stability alone do not determine the susceptibility to this transition in vivo. Rather, superhelical stresses provide long-range coupling among the transition behaviors of all base pairs within a topologically constrained domain. We have developed methods to analyze superhelically induced duplex destabilization (SIDD) in genomic DNA that take into account both this long-range stress-induced coupling and sequence-dependent local thermodynamic stability. Here we apply this approach to examine the SIDD properties of 39 experimentally well-characterized autonomously replicating DNA sequences (ARS elements), which function as replication origins in the yeast Saccharomyces cerevisiae. We find that these ARS elements have a strikingly increased susceptibility to SIDD relative to their surrounding sequences. On average, these ARS elements require 4.78 kcal/mol less free energy to separate than do their immediately surrounding sequences, making them more than 2,000 times easier to open. Statistical analysis shows that the probability of this strong an association between SIDD sites and ARS elements arising by chance is approximately 4 × 10(−10). This local enhancement of the propensity to separate to single strands under superhelical stress has obvious implications for origin function. SIDD properties also could be used, in conjunction with other known origin attributes, to identify putative replication origins in yeast, and possibly in other metazoan genomes

Can one predict DNA Transcription Start Sites by studying bubbles?

It has been speculated that bubble formation of several base-pairs due to thermal fluctuations is indicatory for biological active sites. Recent evidence, based on experiments and molecular dynamics (MD) simulations using the Peyrard-Bishop-Dauxois model, seems to point in this direction. However, sufficiently large bubbles appear only seldom which makes an accurate calculation difficult even for minimal models. In this letter, we introduce a new method that is orders of magnitude faster than MD. Using this method we show that the present evidence is unsubstantiated.Comment: 4 pages, 3 figures, accepted for publication in physical review letter

Superhelical Destabilization in Regulatory Regions of Stress Response Genes

Stress-induced DNA duplex destabilization (SIDD) analysis exploits the known structural and energetic properties of DNA to predict sites that are susceptible to strand separation under negative superhelical stress. When this approach was used to calculate the SIDD profile of the entire Escherichia coli K12 genome, it was found that strongly destabilized sites occur preferentially in intergenic regions that are either known or inferred to contain promoters, but rarely occur in coding regions. Here, we investigate whether the genes grouped in different functional categories have characteristic SIDD properties in their upstream flanks. We report that strong SIDD sites in the E. coli K12 genome are statistically significantly overrepresented in the upstream regions of genes encoding transcriptional regulators. In particular, the upstream regions of genes that directly respond to physiological and environmental stimuli are more destabilized than are those regions of genes that are not involved in these responses. Moreover, if a pathway is controlled by a transcriptional regulator whose gene has a destabilized 5′ flank, then the genes (operons) in that pathway also usually contain strongly destabilized SIDD sites in their 5′ flanks. We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria. These results suggest that strong SIDD sites 5′ to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity. We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes

SIDDBASE: a database containing the stress-induced DNA duplex destabilization (SIDD) profiles of complete microbial genomes

Prokaryotic genomic DNA is generally negatively supercoiled in vivo. Many regulatory processes, including the initiation of transcription, are known to depend on the superhelical state of the DNA substrate. The stresses induced within DNA by negative superhelicity can destabilize the DNA duplex at specific sites. Various experiments have either shown or suggested that stress-induced DNA duplex destabilization (SIDD) is involved in specific regulatory mechanisms governing a variety of biological processes. We have developed methods to evaluate the SIDD properties of DNA sequences, including complete chromosomes. This analysis predicts the locations where the duplex becomes destabilized under superhelical stress. Previous studies have shown that the SIDD-susceptible sites predicted in this way occur at rates much higher than expected at random in transcriptional regulatory regions, and much lower than expected in coding regions. Analysis of the SIDD profiles of 42 bacterial genomes chosen for their diversity confirms this pattern. Predictions of SIDD sites have been used to identify potential genomic regulatory regions, and suggest both possible regulatory mechanisms involving stress-induced destabilization and experimental tests of these mechanisms. Here we describe the SIDDBASE database which enables users to retrieve and visualize the results of SIDD analyses of completely sequenced prokaryotic and archaeal genomes, together with their annotations. SIDDBASE is available at

Integral Mass Balance (IMB) Method for Measuring Multicomponent Gas Adsorption Equilibria in Nanoporous Materials

© 2020 American Chemical Society. To assess the performance of an adsorbent for a particular gas separation, and for process design, it is necessary to determine multicomponent gas adsorption equilibria, either experimentally or from predictions based on models or theory. The experimental techniques commonly used for this purpose, however, are time-consuming and typically require large samples. In this article, we describe a new approach, called the Integral Mass Balance (IMB) method, which combines the controlled flow of a gas mixture with in situ gravimetric measurement and gas composition analysis using quadrupole mass spectrometry. The IMB method allows very rapid equilibrium multicomponent gas adsorption measurements to be performed on samples weighing only a few grams. The method is demonstrated and validated by performing binary O2/N2 adsorption measurements on a commercial 5A zeolite, at ambient temperature and a total pressure of 0.915 MPa. Excellent agreement with previously published data was found, using a 3.5 g sample, with a measurement time of only 4 h for a 20 point isotherm. In contrast, other techniques of equivalent accuracy would require around 20 days of experimental effort to collect a comparable amount of data. Selectivities were also calculated and shown to agree with previously published results. In principle, the technique could readily be extended to measure gas adsorption from ternary or higher mixtures

Aynak : a world-class sediment-hosted copper deposit, Afghanistan

The Aynak copper deposit, located 30 km south of Kabul in Afghanistan, was discovered by Soviet geologists in the 1970s. Extensive exploration undertaken in the area between 1974-80 included several hundred boreholes, seventy trenches and nine exploratory adits. This delineated several large ore bodies and smaller lenses with a total “drill-indicated resource” of 240 Mt at 2.3% Cu (ESCAP, 1995). The mineralisation at Aynak consists of disseminated bornite and chalcopyrite, mainly concentrated in a stratabound orebody in a cyclic succession of metamorphosed dolomites, marls, siltstones and carbonaceous pelites. A model proposes Cu was leached from underlying volcanic rocks and flowed up faults to deposit Cu sulphides into overlying sediments

P5_2 Spaghettification: Surviving a Black Hole Event Horizon

We found that it is possible to stay conscious falling through the event horizon of aBlack Hole if the mass exceeds 19,000M_sol. This assumes the average person is ofgood health and can stay conscious with a relative force less than 5 g acting upon them