A biofilm can be defined as a community of microorganisms adhering to a surface and surrounded by a complex matrix of extrapolymeric substances. It is now generally accepted that the biofilm growth ...mode induces microbial resistance to disinfection that can lead to substantial economic and health concerns. Although the precise origin of such resistance remains unclear, different studies have shown that it is a multifactorial process involving the spatial organization of the biofilm. This review will discuss the mechanisms identified as playing a role in biofilm resistance to disinfectants, as well as novel anti-biofilm strategies that have recently been explored.
There is intense interest in fMRI research on whole-brain functional connectivity, and however, two fundamental issues are still unresolved: the impact of spatiotemporal data resolution (spatial ...parcellation and temporal sampling) and the impact of the network construction method on the reliability of functional brain networks. In particular, the impact of spatiotemporal data resolution on the resulting connectivity findings has not been sufficiently investigated. In fact, a number of studies have already observed that functional networks often give different conclusions across different parcellation scales. If the interpretations from functional networks are inconsistent across spatiotemporal scales, then the whole validity of the functional network paradigm is called into question. This paper investigates the consistency of resting state network structure when using different temporal sampling or spatial parcellation, or different methods for constructing the networks. To pursue this, we develop a novel network comparison framework based on persistent homology from a topological data analysis. We use the new network comparison tools to characterize the spatial and temporal scales under which consistent functional networks can be constructed. The methods are illustrated on Human Connectome Project data, showing that the DISCOH2 network construction method outperforms other approaches at most data spatiotemporal resolutions.
Lucitanib is a potent, oral inhibitor fibroblast growth factor receptor types 1 and 2 (FGFR), vascular endothelial growth factor receptor types 1, 2, and 3 (VEGFR), platelet-derived growth factor ...receptor types α and β (PGFRα/β), which are essential kinases for tumor growth, survival, migration, and angiogenesis. Several tumor types, including breast carcinoma, demonstrate amplification of fibroblast growth factor (FGF)-related genes. There are no approved drugs for molecularly defined FGF-aberrant (FGFR1- or FGF3/4/19-amplified) tumors.
This open-label phase I/IIa study involved a dose-escalation phase to determine maximum tolerated dose (MTD), recommended dose (RD), and pharmacokinetics of lucitanib in patients with advanced solid tumors, followed by a dose-expansion phase to obtain preliminary evidence of efficacy in patients who could potentially benefit from treatment (i.e. with tumors harboring FGF-aberrant pathway or considered angiogenesis-sensitive).
Doses from 5 to 30 mg were evaluated with dose-limiting toxic effects dominated by vascular endothelial growth factor (VEGF) inhibition-related toxic effects at the 30 mg dose level (one case of grade 4 depressed level of consciousness and two cases of grade 3 thrombotic microangiopathy). The most common adverse events (all grades, all cohorts) were hypertension (91%), asthenia (42%), and proteinuria (57%). Exposure increased with dose and t½ was 31–40 h, suitable for once daily administration. Seventy-six patients were included. All but one had stage IV; 42% had >3 lines of previous chemotherapy. Sixty-four patients were assessable for response; 58 had measurable disease. Clinical activity was observed at all doses tested with durable Response Evaluation Criteria In Solid Tumors (RECIST) partial responses in a variety of tumor types. In the angiogenesis-sensitive group, objective RECIST response rate (complete response + partial response) was 26% (7 of 27) and progression-free survival (PFS) was 25 weeks. In assessable FGF-aberrant breast cancer patients, 50% (6 of 12) achieved RECIST partial response with a median PFS of 40.4 weeks for all treated patients.
Lucitanib has promising efficacy and a manageable side-effect profile. The spectrum of activity observed demonstrates clinical benefit in both FGF-aberrant and angiogenesis-sensitive populations. A comprehensive phase II program is planned.
A Finite Element Model (FEM) was developed to evaluate the stresses induced by the thermal cycling in a typical plasma-sprayed thermal barrier coating system (TBCs). The thermo-mechanical model of ...this multi-layer system takes into account the effects of thermal and mechanical properties, morphology of the top-coat/bond-coat interface and oxidation on the local stresses that are responsible for the micro-crack nucleation during cooling, especially near the metal/ceramic interface.
Two top-coat/bond-coat geometries corresponding to different interfacial asperity morphologies (semicircle or sinusoidal) are modeled considering a two dimensional and periodic geometry. The effect of the geometry and the amplitude of asperities on stress distribution are examined to study the cause of the subsequent delamination of the TBCs system. Moreover, the effect of the creep in all layers and plastic deformation in the bond-coat as well as the oxidation in the perpendicular direction of the top-coat/bond-coat interface are examined toward the stress development and critical sites with respect to possible crack paths. In addition, crack initiation and propagation at the system was predicted.
In this study, a general frictional cohesive zone model (FCZM) dedicated to quasi-brittle fracture is proposed to describe the mechanical response of an interface under combined traction or ...compression and shear loadings. Under combined traction and shear loadings, mixed-mode I+II cohesive zone model, as proposed by Camanho et al. (2003), is used to express the mixed-mode response of the interface and the dependence to the loading path consistent to the one expected in quasi-brittle fracture. Under combined compression and shear loadings, the novelty lies in the proposed coupling between Mode II cohesive behavior and frictional behavior based on the damage level leading to a progressive rising of the frictional stress associated with the softening part of the cohesive behavior of the interface. FCZM thus describes a smooth transition from a cohesive zone to a pure frictional contact zone. Applied to the masonry context, this general FCZM can be fully characterized through two fracture tests carried out on small masonry assemblages. Finally, FCZM is implemented in LMGC90 discrete element code and used to simulate the experimental response of an unilateral cyclic shear test carried out on a triplet of limestone blocks assembled by two mortar joints.
In the Guaymas Basin, the presence of cold seeps and hydrothermal vents in close proximity, similar sedimentary settings and comparable depths offers a unique opportunity to assess and compare the ...functioning of these deep-sea chemosynthetic ecosystems. The food webs of five seep and four vent assemblages were studied using stable carbon and nitrogen isotope analyses. Although the two ecosystems shared similar potential basal sources, their food webs differed: seeps relied predominantly on methanotrophy and thiotrophy via the Calvin-Benson-Bassham (CBB) cycle and vents on petroleum-derived organic matter and thiotrophy via the CBB and reductive tricarboxylic acid (rTCA) cycles. In contrast to symbiotic species, the heterotrophic fauna exhibited high trophic flexibility among assemblages, suggesting weak trophic links to the metabolic diversity of chemosynthetic primary producers. At both ecosystems, food webs did not appear to be organised through predator-prey links but rather through weak trophic relationships among co-occurring species. Examples of trophic or spatial niche differentiation highlighted the importance of species-sorting processes within chemosynthetic ecosystems. Variability in food web structure, addressed through Bayesian metrics, revealed consistent trends across ecosystems. Food-web complexity significantly decreased with increasing methane concentrations, a common proxy for the intensity of seep and vent fluid fluxes. Although high fluid-fluxes have the potential to enhance primary productivity, they generate environmental constraints that may limit microbial diversity, colonisation of consumers and the structuring role of competitive interactions, leading to an overall reduction of food-web complexity and an increase in trophic redundancy. Heterogeneity provided by foundation species was identified as an additional structuring factor. According to their biological activities, foundation species may have the potential to partly release the competitive pressure within communities of low fluid-flux habitats. Finally, ecosystem functioning in vents and seeps was highly similar despite environmental differences (e.g. physico-chemistry, dominant basal sources) suggesting that ecological niches are not specifically linked to the nature of fluids. This comparison of seep and vent functioning in the Guaymas basin thus provides further supports to the hypothesis of continuity among deep-sea chemosynthetic ecosystems.
Within the framework of Discrete Element Modelling of masonry structures, a contact law based on Cohesive Zone Model and Coulomb’s law is proposed to describe the fracture behaviour of mortar joints. ...The contact law is expressed in mixed mode I + II and is based on the cohesive behaviours of pure modes I and II and on the frictional behaviour whose parameters can be estimated from an experimental procedure consisting in two fracture tests. Moreover, it is shown from numerical simulations that the contact law exhibits a load path dependency in agreement with the quasi-brittle behaviour expected for mortar. Finally, a parametric study performed from the simulation of the diagonal compression of a masonry panel shows a good agreement of the obtained load-displacement responses and failure modes compared to experimental results of the literature.
This study proposes a high throughput method based on Confocal Laser Scanning Microscopy (CLSM) combined with the use of 96-wells microtiter plates compatible with high resolution imaging for the ...study of biofilm formation and structure. As an illustration, the three-dimensional structures of biofilms formed by 60 opportunistic pathogens were thus observed and quantified. The results revealed the diversity of biofilm architectures. Specific spatial arrangement such as the mushroom-like structures already described for
Pseudomonas aeruginosa was observed. Other features, such as hollow voids in microcolonies of
Salmonella enterica strain Agona, were identified for the first time. The combined use of microplates and confocal imaging proved to be a good alternative to the other high throughput methods commonly used as it enables the direct,
in
situ, qualitative and quantitative characterization of biofilm architecture. This high content method should lead to a clearer understanding of the structure–function relationships implicated in biofilms traits.
In recent years, driven by scientific and clinical concerns, there has been an increased interest in the analysis of functional brain networks. The goal of these analyses is to better understand how ...brain regions interact, how this depends upon experimental conditions and behavioral measures and how anomalies (disease) can be recognized. In this paper, we provide, first, a brief review of some of the main existing methods of functional brain network analysis. But rather than compare them, as a traditional review would do, instead, we draw attention to their significant limitations and blind spots. Then, second, relevant experts, sketch a number of emerging methods, which can break through these limitations. In particular we discuss five such methods. The first two, stochastic block models and exponential random graph models, provide an inferential basis for network analysis lacking in the exploratory graph analysis methods. The other three addresses: network comparison via persistent homology, time-varying connectivity that distinguishes sample fluctuations from neural fluctuations, and network system identification that draws inferential strength from temporal autocorrelation.
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