A matrix iteration for dynamic network summaries

We propose a new algorithm for summarizing properties of large-scale time-evolving networks. This type of data, recording connections that come and go over time, is being generated in many modern applications, including telecommunications and on-line human social behavior. The algorithm computes a dynamic measure of how well pairs of nodes can communicate by taking account of routes through the network that respect the arrow of time. We take the conventional approach of downweighting for length (messages become corrupted as they are passed along) and add the novel feature of downweighting for age (messages go out of date). This allows us to generalize widely used Katz-style centrality measures that have proved popular in network science to the case of dynamic networks sampled at non-uniform points in time. We illustrate the new approach on synthetic and real data.

A note on the Fredholm properties of Toeplitz operators on weighted Bergman spaces with matrix-valued symbols

We characterize the essential spectra of Toeplitz operators Ta on weighted Bergman spaces with matrix-valued symbols; in particular we deal with two classes of symbols, the Douglas algebra C+H∞ and the Zhu class Q := L∞ ∩VMO∂ . In addition, for symbols in C+H∞ , we derive a formula for the index of Ta in terms of its symbol a in the scalar-valued case, while in the matrix-valued case we indicate that the standard reduction to the scalar-valued case fails to work analogously to the Hardy space case. Mathematics subject classification (2010): 47B35,

Direct observation of membrane insertion by enveloped virus matrix proteins by phosphate displacement

Enveloped virus release is driven by poorly understood proteins that are functional analogs of the coat protein assemblies that mediate intracellular vesicle trafficking. We used differential electron density mapping to detect membrane integration by membrane-bending proteins from five virus families. This demonstrates that virus matrix proteins replace an unexpectedly large portion of the lipid content of the inner membrane face, a generalized feature likely to play a role in reshaping cellular membranes.

Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice. Level of α1-Syntrophin and α-Dystrobrevin in Skeletal Muscles of mdx Mice

Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (<5 kb), truncated recombinant microdystrophin genes with deletions of most of rod and carboxyl-terminal (CT) domains of dystrophin have been developed. We have previously shown the efficiency of mRNA sequence–optimized microdystrophin (ΔR4-23/ΔCT, called MD1) with deletion of spectrin-like repeat domain 4 to 23 and CT domain in ameliorating the pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signalling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain–extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction–induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy.

Data assimilation with correlated observation errors: experiments with a 1-D shallow water model

Remote sensing observations often have correlated errors, but the correlations are typically ignored in data assimilation for numerical weather prediction. The assumption of zero correlations is often used with data thinning methods, resulting in a loss of information. As operational centres move towards higher-resolution forecasting, there is a requirement to retain data providing detail on appropriate scales. Thus an alternative approach to dealing with observation error correlations is needed. In this article, we consider several approaches to approximating observation error correlation matrices: diagonal approximations, eigendecomposition approximations and Markov matrices. These approximations are applied in incremental variational assimilation experiments with a 1-D shallow water model using synthetic observations. Our experiments quantify analysis accuracy in comparison with a reference or ‘truth’ trajectory, as well as with analyses using the ‘true’ observation error covariance matrix. We show that it is often better to include an approximate correlation structure in the observation error covariance matrix than to incorrectly assume error independence. Furthermore, by choosing a suitable matrix approximation, it is feasible and computationally cheap to include error correlation structure in a variational data assimilation algorithm.

Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs

We describe a bioactive lipopeptide that combines the capacity to promote the adhesion and subsequent self-detachment of live cells, using template-cell-environment feedback interactions. This self-assembling peptide amphiphile comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser. Biophysical characterisation revealed that the PA self-assembles into 3 nm diameter spherical micelles above a critical aggregation concentration (cac). In addition, when used in solution at 5–150 nM (well below the cac), the PA is capable of forming film coatings that provide a stable surface for human corneal fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to be sensitive to metalloproteases expressed endogenously by the attached cells, and consequently to elicit the controlled detachment of cells without compromising their viability. As such, this material constitutes a novel class of multi-functional coating for both fundamental and clinical applications in tissue engineering.

Comparative in situ analyses of cell wall matrix polysaccharide dynamics in developing rice and wheat grain

Cell wall polysaccharides of wheat and rice endosperm are an important source of dietary fibre. Monoclonal antibodies specific to cell wall polysaccharides were used to determine polysaccharide dynamics during the development of both wheat and rice grain. Wheat and rice grain present near synchronous developmental processes and significantly different endosperm cell wall compositions, allowing the localisation of these polysaccharides to be related to developmental changes. Arabinoxylan (AX) and mixed-linkage glucan (MLG) have analogous cellular locations in both species, with deposition of AX and MLG coinciding with the start of grain filling. A glucuronoxylan (GUX) epitope was detected in rice, but not wheat endosperm cell walls. Callose has been reported to be associated with the formation of cell wall outgrowths during endosperm cellularisation and xyloglucan is here shown to be a component of these anticlinal extensions, occurring transiently in both species. Pectic homogalacturonan (HG) was abundant in cell walls of maternal tissues of wheat and rice grain, but only detected in endosperm cell walls of rice in an unesterified HG form. A rhamnogalacturonan-I (RG-I) backbone epitope was observed to be temporally regulated in both species, detected in endosperm cell walls from 12 DAA in rice and 20 DAA in wheat grain. Detection of the LM5 galactan epitope showed a clear distinction between wheat and rice, being detected at the earliest stages of development in rice endosperm cell walls, but not detected in wheat endosperm cell walls, only in maternal tissues. In contrast, the LM6 arabinan epitope was detected in both species around 8 DAA and was transient in wheat grain, but persisted in rice until maturity.

Investigating the influence of extracellular matrix and glycolytic metabolism on muscle stem cell migration on their native fibre environment

The composition of the extracellular matrix (ECM) of skeletal muscle fibres is a unique environment that supports the regenerative capacity of satellite cells; the resident stem cell population. The impact of environment has great bearing on key properties permitting satellite cells to carry out tissue repair. In this study, we have investigated the influence of the ECM and glycolytic metabolism on satellite cell emergence and migration- two early processes required for muscle repair. Our results show that both influence the rate at which satellite cells emerge from the sub-basal lamina position and their rate of migration. These studies highlight the necessity of performing analysis of satellite behaviour on their native substrate and will inform on the production of artificial scaffolds intended for medical uses.

Regulation of cell migration in cancer: investigation into the regulation of cancer cell blebbing in the extracellular matrix

Cell migration is a highly coordinated process and any aberration in the regulatory mechanisms could result in pathological conditions such as cancer. The ability of cancer cells to disseminate to distant sites within the body has made it difficult to treat. Cancer cells also exhibit plasticity that makes them able to interconvert from an elongated, mesenchymal morphology to an amoeboid blebbing form under different physiological conditions. Blebs are spherical membrane protrusions formed by actomyosin-mediated contractility of cortical actin resulting in increased hydrostatic pressure and subsequent detachment of the membrane from the cortex. Tumour cells use blebbing as an alternative mode of migration by squeezing through preexisting gaps in the ECM, and bleb formation is believed to be mediated by the Rho-ROCK signaling pathway. However, the involvement of transmembrane water and ion channels in cell blebbing has not been examined. In the present study, the role of the transmembrane water channels, aquaporins, transmembrane ion transporters and lipid signaling enzymes in the regulation of blebbing was investigated. Using 3D matrigel matrix as an in vitro model to mimic normal extracellular matrix, and a combination of confocal and time-lapse microscopy, it was found that AQP1 knockdown by siRNA ablated blebbing of HT1080 and ACHN cells, and overexpression of AQP1-GFP not only significantly increased bleb size with a corresponding decrease in bleb numbers, but also induced bleb formation in non-blebbing cell lines. Importantly, AQP1 overexpression reduces bleb lifespan due to faster bleb retraction. This novel finding of AQP1-facilitated bleb retraction requires the activity of the Na+/H+ pump as inhibition of the ion transporter, which was found localized to intracellular vesicles, blocked bleb retraction in both cell lines. This study also demonstrated that a differential regulation of cell blebbing by AQP isoforms exists as knockdown of AQP5 had no effect on bleb formation. Data from this study also demonstrates that the lipid signaling PLD2 signals through PA in the LPA-LPAR-Rho-ROCK axis to positively regulate bleb formation in both cell lines. Taken together, this work provides a novel role of AQP1 and Na+/H+ pump in regulation of cell blebbing, and this could be exploited in the development of new therapy to treat cancer.

The compositional and configurational heterogeneity of matrix habitats shape woodland carabid communities in wooded-agricultural landscapes

Landscape heterogeneity (the composition and configuration of matrix habitats) plays a major role in shaping species communities in wooded-agricultural landscapes. However, few studies consider the influence of different types of semi-natural and linear habitats in the matrix, despite their known ecological value for biodiversity. Objective To investigate the importance of the composition and configuration of matrix habitats for woodland carabid communities and identify whether specific landscape features can help to maintain long-term populations in wooded-agricultural environments. Methods Carabids were sampled from woodlands in 36 tetrads of 4 km2 across southern Britain. Landscape heterogeneity including an innovative representation of linear habitats was quantified for each tetrad. Carabid community response was analysed using ordination methods combined with variation partitioning and additional response trait analyses. Results Woodland carabid community response was trait-specific and better explained by simultaneously considering the composition and configuration of matrix habitats. Semi-natural and linear features provided significant refuge habitat and functional connectivity. Mature hedgerows were essential for slow-dispersing carabids in fragmented landscapes. Species commonly associated with heathland were correlated with inland water and woodland patches despite widespread heathland conversion to agricultural land, suggesting that species may persist for some decades when elements representative of the original habitat are retained following landscape modification. Conclusions Semi-natural and linear habitats have high biodiversity value. Landowners should identify features that can provide additional resources or functional connectivity for species relative to other habitat types in the landscape matrix. Agri-environment options should consider landscape heterogeneity to identify the most efficacious changes for biodiversity.

On mathematical and physical principles of transformations of the coherent radar backscatter matrix

The congruential rule advanced by Graves for polarization basis transformation of the radar backscatter matrix is now often misinterpreted as an example of consimilarity transformation. However, consimilarity transformations imply a physically unrealistic antilinear time-reversal operation. This is just one of the approaches found in literature to the description of transformations where the role of conjugation has been misunderstood. In this paper, the different approaches are examined in particular in respect to the role of conjugation. In order to justify and correctly derive the congruential rule for polarization basis transformation and properly place the role of conjugation, the origin of the problem is traced back to the derivation of the antenna height from the transmitted field. In fact, careful consideration of the role played by the Green’s dyadic operator relating the antenna height to the transmitted field shows that, under general unitary basis transformation, it is not justified to assume a scalar relationship between them. Invariance of the voltage equation shows that antenna states and wave states must in fact lie in dual spaces, a distinction not captured in conventional Jones vector formalism. Introducing spinor formalism, and with the use of an alternate spin frame for the transmitted field a mathematically consistent implementation of the directional wave formalism is obtained. Examples are given comparing the wider generality of the congruential rule in both active and passive transformations with the consimilarity rule.

The “pain matrix” in pain-free individuals

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations

Wear of Ball Attachments After 1 to 8 Years of Clinical Use: A Qualitative Analysis

The purpose of this study was to analyze and compare scanning electron microscopy (SEM) observations of ball attachments that had been worn by patients during three periods of clinical use. One hundred forty-four specimens of ball anchor attachments (gold alloy matrix and titanium patrix) were studied by SEM after periods of approximately 1, 3.5, and 8 years of clinical use. Twenty new attachment components were examined as controls. SEM images revealed signs of mechanical wear for the ball attachments studied. The surfaces of the titanium patrix were associated primarily with roughening after short-term use, whereas surfaces of the gold alloy matrix showed wear, roughening, and loss of microscopic material in the form of flakes. Severe mechanical wear on both surfaces was noted after longer periods of use. The mechanical changes were not correlated with patient-mediated observations regarding the time-dependent retentive efficacy of the attachments. One year of clinical wear appeared to have limited effect on the ball attachment tested. Conversely, longer periods of use led to marked modifications in shape of the matrix and patrix components. Int J Prosthodont 2011;24:270-272.

Acellular Dermal Matrix Graft for Gingival Augmentation: A Preliminary Clinical, Histologic, and Ultrastructural Evaluation

Background: The aim of this study was to evaluate clinically, histologically, and ultrastructurally the integration process of the acellular dermal matrix used to increase the band of keratinized tissue while achieving gingival inflammation control. Methods: Ten patients exhibiting a mucogingival problem with bands of keratinized tissue <= 1 mm and gingival inflammation of the related teeth were included in the study. The surgical procedures were performed to augment the gingival tissue using acellular dermal matrix. Clinical measurements were assessed at baseline and after 3 months. A specimen of the allograft and surrounding tissues was obtained immediately before the surgery and 4 minutes and 1, 2, 3, 4, 6, and 10 weeks after grafting. Results: Clinically, a gain of keratinized tissue of 2.92 +/- 0.65 mm was observed after 3 months. Histologically and ultrastructurally, many macrophages were observed phagocytosing preexisting collagen fibers in the first weeks. From week 2 on, fibroblasts synthesizing new collagen, epithelial cells colonizing the graft surface, and revascularization were noticed. After 6 weeks it was difficult to find the acellular dermal matrix preexisting collagen fibers. This process of substitution was completed after 10 weeks, when the reepithelialization of the entire graft throughout a well-structured basement membrane was achieved. Conclusion: The acellular dermal matrix graft seemed to be an easily handled material for use in keratinized tissue augmentation that, in humans, was substituted and completely reepithelialized in 10 weeks according to histologic and ultrastructural results. J Periodontol 2009;80:253-259.

Ridge Preservation With Acellular Dermal Matrix and Anorganic Bone Matrix Cell-Binding Peptide P-15 After Tooth Extraction in Humans

Background: Preventing ridge collapse with the extraction of maxillary anterior teeth is vital to an esthetic restorative result. Several regenerative techniques are available and are used for socket preservation. The aim of this study is to analyze by clinical parameters the use of acellular dermal matrix (ADM) and anorganic bovine bone matrix (ABM) with synthetic cell-binding peptide P-15 to preserve alveolar bone after tooth extraction. Methods: Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15) or the control group (ADM only). Clinical measurements were recorded initially and at 6 months after ridge-preservation procedures. Results: In the clinical measurements (external vertical palatal measurement [EVPM], external vertical buccal measurement [EVBM], and alveolar horizontal measurement [AHM]) the statistical analysis showed no difference between test and control groups initially and at 6 months. The intragroup analysis, after 6 months, showed a statistically significant reduction in the measurements for both groups. In the comparison between the two groups, the differences in the test group were as follows: EVPM = 0.83 +/- 1.53 mm; EVBM = 1.20 +/- 2.02 mm; and AHM = 2.53 +/- 1.81 mm. The differences in the control group were as follows: EVPM = 0.87 +/- 1.13 mm; EVBM = 1.50 +/- 1.15 mm; and AHM = 3.40 +/- 1.39 mm. The differences in EVPM and EVBM were not statistically significant; however, in horizontal measurement (AHM), there was a statistically significant difference (P<0.05). Conclusion: The results of this study show that ADM used as membrane associated with ABM/P-15 can be used to reduce buccal-palatal dimensions compared to ADM alone for preservation of the alveolar ridge after extraction of anterior maxillary teeth. J Periodontol 2011;82:72-79.