Identification of collagenolytic MMP networks as potential biomarkers in progressive chronic periodontitis subjects and MMP-8 null allele model

Chronic periodontitis results from a complex aetiology, including the formation of a subgingival biofilm and the elicitation of the host s immune and inflammatory response. The hallmark of chronic periodontitis is alveolar bone loss and soft periodontal tissue destruction. Evidence supports that periodontitis progresses in dynamic states of exacerbation and remission or quiescence. The major clinical approach to identify disease progression is the tolerance method, based on sequential probing. Collagen degradation is one of the key events in periodontal destructive lesions. Matrix metalloproteinase (MMP)-8 and MMP-13 are the primary collagenolytic MMPs that are associated with the severity of periodontal inflammation and disease, either by a direct breakdown of the collagenised matrix or by the processing of non-matrix bioactive substrates. Despite the numerous host mediators that have been proposed as potential biomarkers for chronic periodontitis, they reflect inflammation rather than the loss of periodontal attachment. The aim of the present study was to determine the key molecular MMP-8 and -13 interactions in gingival crevicular fluid (GCF) and gingival tissue from progressive periodontitis lesions and MMP-8 null allele mouse model. In study (I), GCF and gingival biopsies from active and inactive sites of chronic periodontitis patients, which were determined clinically by the tolerance method, and healthy GCF were analysed for MMP-13 and tissue inhibitor of matrix metalloproteinases (TIMP)-1. Chronic periodontitis was characterised by increased MMP-13 levels and the active sites showed a tendency of decreased TIMP-1 levels associated with increments of MMP-13 and total protein concentration compared to inactive sites. In study (II), we investigated whether MMP-13 activity was associated with TIMP-1, bone collagen breakdown through ICTP levels, as well as the activation rate of MMP-9 in destructive lesions. The active sites demonstrated increased GCF ICTP levels as well as lowered TIMP-1 detection along with elevated MMP-13 activity. MMP-9 activation rate was enhanced by MMP-13 in diseased gingival tissue. In study (III), we analysed the potential association between the levels, molecular forms, isoenzyme distribution and degree of activation of MMP-8, MMP-14, MPO and the inhibitor TIMP-1 in GCF from periodontitis progressive patients at baseline and after periodontal therapy. A positive correlation was found for MPO/MMP-8 and their levels associated with progression episodes and treatment response. Because MMP-8 is activated by hypochlorous acid in vitro, our results suggested an interaction between the MPO oxidative pathway and MMP-8 activation in GCF. Finally, in study (IV), on the basis of the previous finding that MMP-8-deficient mice showed impaired neutrophil responses and severe alveolar bone loss, we aimed to characterise the detection patterns of LIX/CXCL5, SDF-1/CXCL12 and RANKL in P. gingivalis-induced experimental periodontitis and in the MMP-8-/- murine model. The detection of neutrophil-chemoattractant LIX/CXCL5 was restricted to the oral-periodontal interface and its levels were reduced in infected MMP-8 null mice vs. wild type mice, whereas the detection of SDF-1/CXCL12 and RANKL in periodontal tissues increased in experimentally-induced periodontitis, irrespectively from the genotype. Accordingly, MMP-8 might regulate LIX/CXCL5 levels by undetermined mechanisms, and SDF-1/CXCL12 and RANKL might promote the development and/or progression of periodontitis.

Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies

Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a ID sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods. (C) 2012 Elsevier Masson SAS. All rights reserved.

Progressive fusion of reconstruction algorithms for low latency applications in compressed sensing

Recently, it has been shown that fusion of the estimates of a set of sparse recovery algorithms result in an estimate better than the best estimate in the set, especially when the number of measurements is very limited. Though these schemes provide better sparse signal recovery performance, the higher computational requirement makes it less attractive for low latency applications. To alleviate this drawback, in this paper, we develop a progressive fusion based scheme for low latency applications in compressed sensing. In progressive fusion, the estimates of the participating algorithms are fused progressively according to the availability of estimates. The availability of estimates depends on computational complexity of the participating algorithms, in turn on their latency requirement. Unlike the other fusion algorithms, the proposed progressive fusion algorithm provides quick interim results and successive refinements during the fusion process, which is highly desirable in low latency applications. We analyse the developed scheme by providing sufficient conditions for improvement of CS reconstruction quality and show the practical efficacy by numerical experiments using synthetic and real-world data. (C) 2013 Elsevier B.V. All rights reserved.

Mechanism on Progressive Failure of a Faulted Rock Slope Due to Slip-Weakening

Slip-weakening is one of the characteristics of geological materials under certain loadings. Non-uniform rock structure may exist in the vicinity of the slip surface for a rock slope. Some portion of the slip surface may be penetrated but the other not. For the latter case, the crack or the fault surface will undergo shear deformation before it becomes a successive surface under a certain loading. As the slipped portion advances,slip-weakening occurs over a distance behind the crack tip. In the weakening zone, the shear strength will decrease from its peak value to residual friction level. The stress will redistribute along the surface of crack and in the weakening zone. Thus the changed local stress concentration leads the crack to extend and the ratio of penetration of the slip surface to increase. From the view of large-scale for the whole slip surface, the shear strength will decrease due to the damage of interior rock structure, and the faulted rock behaves as a softening material. Such a kind of mechanism performs in a large number of practical landslides in the zones experienced strong earthquakes. It should be noted that the mechanism mentioned above is different from that of the breakage of structural clay,in which the geological material is regarded as a medium containing structural lumps and structural bands. In this paper, the softening behavior of a faulted rock should be regarded as a comprehensive result of the whole complicated process including slip-weakening, redistribution of stress, extension of crack tip, and the penetration of the slip surface. This process is accompanied by progressive failure and abrupt structural damage. The size of slip-weakening zone is related to the undergoing strain. Once the relative slide is initiated (local or integrated), the effect of slip-weakening will behave in a certain length behind the crack tip until the formation of the whole slip surface.

Weak Zone Related Seismic Cycles in Progressive Failure Leading to Collapse in Brittle Crust

Until quite recently our understanding of the basic mechanical process responsible for earthquakes and faulting was not well known. It can be argued that this was partly a consequence of the complex nature of fracture in crust and in part because evidence of brittle phenomena in the natural laboratory of the earth is often obliterated or obscured by other geological processes. While it is well understood that the spatial and temporal complexity of earthquakes and the fault structures emerge from geometrical and material built-in heterogeneities, one important open question is how the shearing becomes localized into a band of intense fractures. Here the authors address these questions through a numerical approach of a tectonic plate by considering rockmass heterogeneity both in microscopic scale and in mesoscopic scale. Numerical simulations of the progressive failure leading to collapse under long-range slow driving forces in the far-field show earthquake-like rupture behavior. $En Echelon$ crack-arrays are reproduced in the numerical simulation. It is demonstrated that the underlying fracturing induced acoustic emissions (or seismic events) display self-organized criticality------from disorder to order. The seismic cycles and the geometric structures of the fracture faces, which are found greatly depending on the material heterogeneity (especially on the macroscopic scale), agree with that observed experimentally in real brittle materials. It is concluded that in order to predict a main shock, one must have extremely detailed knowledge on very minor features of the earth's crust far from the place where the earthquake originated. If correct, the model proposed here seemingly provides an explanation as to why earthquakes to date are not predicted so successfully. The reason is not that the authors do not understand earthquake mechanisms very well but that they still know little about our earth's crust.

The island of Kauai, Hawaii's progressive shoreline setback and coastal protection ordinance

Approximately two-thirds of coastal and Great Lakes states have some type of shoreline construction setback or construction control line requiring development to be a certain distance from the shoreline or other coastal feature (OCRM, 2008). Nineteen of 30 coastal states currently use erosion rates for new construction close to the shoreline. Seven states established setback distances based on expected years from the shoreline: the remainder specify a fixed setback distance (Heinz Report, 2000). Following public hearings by the County of Kauai Planning Commission and Kauai County Council, the ‘Shoreline Setback and Coastal Protection Ordinance’ was signed by the Mayor of Kauai on January 25, 2008. After a year of experience implementing this progressive, balanced shoreline setback ordinance several amendments were recently incorporated into the Ordinance (#887; Bill #2319 Draft 3). The Kauai Planning Department is presently drafting several more amendments to improve the effectiveness of the Ordinance. The intent of shoreline setbacks is to establish a buffer zone to protect shorefront development from loss due to coastal erosion - for a period of time; to provide protection from storm waves; to allow the natural dynamic cycles of erosion and accretion of beaches and dunes to occur; to maintain beach and dune habitat; and, to maintain lateral beach access and open space for the enjoyment of the natural shoreline environment. In addition, a primary goal of the Kauai setback ordinance is to avoid armoring or hardening of the shore which along eroding coasts has been documented to ultimately eliminate the fronting beach. (PDF contains 4 pages)

Progressive Decrease in the Potential Usefulness of Meningococcal Serogroup B Vaccine (4CMenB, Bexsero (R)) in Gipuzkoa, Northern Spain

The effectiveness of a vaccine is determined not only by the immunogenicity of its components, but especially by how widely it covers the disease-causing strains circulating in a given region. Because vaccine coverage varies over time, this study aimed to detect possible changes that could affect vaccine protection during a specific period in a southern European region. The 4CMenB vaccine is licensed for use in Europe, Canada, and Australia and is mainly directed against Neisseria meningitidis serogroup B. This vaccine contains four main immunogenic components: three recombinant proteins, FHbp, Nhba and NadA, and an outer membrane vesicle [PorA P1.4]. The allelic distribution of FHbp, Nhba, NadA, and PorA antigens in 82 invasive isolates (B and non-B serogroups) isolated from January 2008 to December 2013 were analyzed. 4CMenB was likely protective against 61.8% and 50% of serogroup B and non-B meningococci, respectively, in the entire period, but between 2012 and 2013, the predicted protection fell below 45% (42.1% for serogroup B isolates). The observed decreasing trend in the predicted protection during the 6 years of the study (X-2 for trend = 4.68, p=0.03) coincided with a progressive decrease of several clonal complexes (e. g., cc11, cc32 and cc41/44), which had one or more antigens against which the vaccine would offer protection.