ALBERT

Description: Natural transformation (NT) in bacteria is a complex process, including binding, uptake, transport and recombination of exogenous DNA into the chromosome, consequently generating genetic diversity and driving evolution. DNA processing protein A (DprA), which is distributed among virtually all bacterial species, is involved in binding to the internalized single-stranded DNA (ssDNA) and promoting the loading of RecA on ssDNA during NTs. Here we present the structures of DNA_processg_A (DprA) domain of the Helicobacter pylori DprA (HpDprA) and its complex with an ssDNA at 2.20 and 1.80 Å resolutions, respectively. The complex structure revealed for the first time how the conserved DprA domain binds to ssDNA. Based on structural comparisons and binding assays, a unique ssDNA-binding mode is proposed: the dimer of HpDprA binds to ssDNA through two small, positively charged binding pockets of the DprA domains with classical Rossmann folds and the key residue Arg52 is re-oriented to ‘open’ the pocket in order to accommodate one of the bases of ssDNA, thus enabling HpDprA to grasp substrate with high affinity. This mode is consistent with the oligomeric composition of the complex as shown by electrophoretic mobility-shift assays and static light scattering measurements, but differs from the direct polymeric complex of Streptococcus pneumoniae DprA–ssDNA.

Description: An exact analytical solution is presented for the effective dynamic transverse shear modulus in a heterogeneous fluid-filled porous solid containing cylindrical inclusions. The complex and frequency-dependent properties of the dynamic shear modulus are caused by the physical mechanism of mesoscopic-scale wave-induced fluid flow whose scale is smaller than wavelength but larger than the size of pores. Our model consists of three phases: a long cylindrical inclusion, a cylindrical shell of poroelastic matrix material with different mechanical and/or hydraulic properties than the inclusion and an outer region of effective homogeneous medium of laterally infinite extent. The behavior of both the inclusion and the matrix is described by Biot's consolidation equations, whereas the surrounding effective medium which is used to describe the effective transverse shear properties of the inner poroelastic composite is assumed to be a viscoelastic solid whose complex transverse shear modulus needs to be determined. The determined effective transverse shear modulus is used to quantify the S -wave attenuation and velocity dispersion in heterogeneous fluid-filled poroelastic rocks. The calculation shows the relaxation frequency and relative position of various fluid saturation dispersion curves predicted by this study exhibit very good agreement with those of a previous 2-D finite-element simulation. For the double-porosity model (inclusions having a different solid frame than the matrix but the same pore fluid as the matrix) the effective shear modulus also exhibits a size-dependent characteristic that the relaxation frequency moves to lower frequencies by two orders of magnitude if the radius of the cylindrical poroelastic composite increases by one order of magnitude. For the patchy-saturation model (inclusions having the same solid frame as the matrix but with a different pore fluid from the matrix), the heterogeneity in pore fluid cannot cause any attenuation in the transverse shear modulus at all. A comparison with the case of spherical inclusions illustrates that the transverse shear modulus for the cylindrical inclusion exhibits more S -wave attenuation than spherical inclusions.

Description: This paper is concerned with the issue of passivity analysis for switched generalized neural networks (SGNNs). Parametric uncertainty is considered and assumed to be time-variant and norm bounded. We first give the passivity condition for SGNNs without uncertainties, and then extend the result to the cases with time-varying parametric uncertainties both in network parameters and output matrices. By using the Lyapunov–Krasovskii functional and some analysis techniques, the passivity criteria are presented in terms of linear matrix inequalities. Two numerical examples are given to show the effectiveness of the theoretical results.

Description: Motivation: How chromatin folds in three-dimensional (3D) space is closely related to transcription regulation. As powerful tools to study such 3D chromatin conformation, the recently developed Hi-C technologies enable a genome-wide measurement of pair-wise chromatin interaction. However, methods for the detection of biologically meaningful chromatin interactions, i.e. peak calling, from Hi-C data, are still under development. In our previous work, we have developed a novel hidden Markov random field (HMRF) based Bayesian method, which through explicitly modeling the non-negligible spatial dependency among adjacent pairs of loci manifesting in high resolution Hi-C data, achieves substantially improved robustness and enhanced statistical power in peak calling. Superior to peak callers that ignore spatial dependency both methodologically and in performance, our previous Bayesian framework suffers from heavy computational costs due to intensive computation incurred by modeling the correlated peak status of neighboring loci pairs and the inference of hidden dependency structure. Results: In this work, we have developed FastHiC, a novel approach based on simulated field approximation, which approximates the joint distribution of the hidden peak status by a set of independent random variables, leading to more tractable computation. Performance comparisons in real data analysis showed that FastHiC not only speeds up our original Bayesian method by more than five times, bus also achieves higher peak calling accuracy. Availability and Implementation: FastHiC is freely accessible at: http://www.unc.edu/~yunmli/FastHiC/ Contacts : yunli@med.unc.edu or ming.hu@nyumc.org Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant ( P 〈 5.0 x 10 –8 ) associations with blood pressure, which included variants at three new loci ( CACNA1D , CYP21A2 , and MED13L ) and a newly discovered variant near SLC4A7 . We also replicated 14 previously reported loci, 8 ( CASZ1 , MOV10 , FGF5 , CYP17A1 , SOX6 , ATP2B1 , ALDH2 , and JAG1 ) at genome-wide significance, and 6 ( FIGN , ULK4 , GUCY1A3 , HFE , TBX3-TBX5 , and TBX3 ) at a suggestive level of P = 1.81 x 10 –3 to 5.16 x 10 –8 . These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Description: The antipredatory responses/attachment behaviour of the green-lipped mussel Perna viridi s were studied under combined stresses of hypoxia and low salinity in the presence/absence of its predator, the swimming crab Thalamita danae . There were two oxygen concentrations (1.5 mg l –1 O 2 = hypoxic and 6.0 mg l –1 O 2 = normoxic) and two salinity levels (15 = low, 30 = normal). Byssus production performances (including byssal-thread number, byssal-thread diameter, byssal-thread length, cumulative byssal-thread length and volume and frequency of stalk-shedding) were evaluated after 48 h. All variables were significantly affected by dissolved oxygen (DO), salinity and predator presence. Interactive effects of these three factors on byssus production were also observed. Byssus production and frequency of stalk-shedding were lowest in hypoxia x low salinity, followed by normoxia x low salinity, hypoxia x normal salinity, while normoxia x normal salinity exhibited the highest values in both predator-presence and non-predator-presence groups. At each treatment of DO and salinity, all parameters in predator-presence groups were significantly higher than in non-predator-presence groups. Our results indicate that the environmental hypoxia and low salinity impair anti-predatory/attachment behaviour and show some synergistic effects. Since reduced byssus production makes the mussels more vulnerable to crab predators, the co-occurrence of hypoxia and low salinity may increase the rates of crab predation on P. viridi s in the field.

Description: Doubly hidden Markov models (DHMMs) have been widely used to analyze a type of time process whose driving factors are hierarchical and hierarchically correlated. A common issue of these models is that they implicitly assume that the dwell time of any system state is constant or exponentially distributed. This property comes from the standard hidden Markov models and causes the DHMM to limitations in some actual application environment, where an application has latent temporal structure and does not follow the exponential distribution but has the period-like or variable-period feature. Such problems are frequently encountered in practice, e.g. network traffic. In this paper, we remove this limitation by a new structural discrete approach named nested hidden semi-Markov model. The proposed model includes a nested latent semi-Markov chain and one observable discrete stochastic process. The bottom latent semi-Markov chain is the core layer and controls the second-layer semi-Markov chain that generates the observable process. The state duration of both the semi-Markov chains can be variable or explicit. The model makes no assumptions on the distribution of the state-duration and the observable processes. An efficient forward and backward recursion procedure is developed for estimating the generator of the proposed model and inferring the underlying state processes for a given observation sequence. To evaluate the performance of the proposed model, we apply the model to the arrival process of network traffic and compare its simulation traffic and the real traffic. The performance evaluation in the experiments includes time dynamic process, auto-correlation, cross-correlation, statistical distribution and self-similarity.

Description: We have developed a new, sequence-specific DNA labeling strategy that will dramatically improve DNA mapping in complex and structurally variant genomic regions, as well as facilitate high-throughput automated whole-genome mapping. The method uses the Cas9 D10A protein, which contains a nuclease disabling mutation in one of the two nuclease domains of Cas9, to create a guide RNA-directed DNA nick in the context of an in vitro -assembled CRISPR-CAS9-DNA complex. Fluorescent nucleotides are then incorporated adjacent to the nicking site with a DNA polymerase to label the guide RNA-determined target sequences. This labeling strategy is very powerful in targeting repetitive sequences as well as in barcoding genomic regions and structural variants not amenable to current labeling methods that rely on uneven distributions of restriction site motifs in the DNA. Importantly, it renders the labeled double-stranded DNA available in long intact stretches for high-throughput analysis in nanochannel arrays as well as for lower throughput targeted analysis of labeled DNA regions using alternative methods for stretching and imaging the labeled long DNA molecules. Thus, this method will dramatically improve both automated high-throughput genome-wide mapping as well as targeted analyses of complex regions containing repetitive and structurally variant DNA.

Description: Cloud security is a major concern that may delay its widespread adoption. User access control (UAC) is the core component of security in cloud computing environment, aiming to ensure that stored data are allowed to be accessed only by authenticated/authorized users. As a typical behavioural biometrics, keystroke dynamics provides a promising UAC solution. The most challenging issue that hinders the wide deployment of keystroke is the high verification error rate. Gunetti et al. proposed a classical n -graph-based keystroke verification method (GP method), which can achieve a low False Acceptance Rate (FAR). However, the GP method suffers from a high False Rejection Rate (FRR) and a severe scalability issue. Thus, GP is not a feasible solution for computing cloud application where scalability is a big issue. In this paper, two keystroke verification approaches ( n Gdv-V and n Gdv-C) are proposed to overcome GP's shortcomings. To reduce high FRR, we designed a new correlation measure using n -graph equivalent feature ( n Gdv) that enables more accurate recognition for genuine users. Moreover, correlation-based hierarchical clustering is proposed to address the scalability issue. The experimental results show that the n Gdv-C can produce much lower FRR while achieving almost the same level of FAR as that of the GP method. Furthermore, 1250 times (when using n Gdv-V) and three times (when using n Gdv-C(17,4)) authentication speed gains have been achieved.

Description: In this paper, we first establish some new lower bounds for the first eigenvalue of the f -Laplacian on closed Riemannian manifolds with the N -Bakry–Émery Ricci curvature satisfying Ric N f ≥ K ( K R), which not only improve the classical results of lower bounds for the first eigenvalue of the Laplacian, but also are suitable for both smooth metric spaces and quasi-Einstein manifolds. Then we obtain the corresponding lower bounds for closed manifolds with Ric f ≥ K ( K R), which include gradient Ricci solitons. As an application, we derive a universal lower bound for the diameter of compact non-trivial shrinking Ricci solitons, which improves the results of Andrews–Ni [1] and Futaki–Sano [9].