Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1β, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.     

Flexibility and binding affinity in protein–ligand,protein–protein and multi-component protein interactions: limitations of current computational approaches

The recognition process between a protein and a partner represents a significant theoretical challenge. In silico structure-based drug design carried out with nothing more than the three-dimensional structure of the protein has led to the introduction of many compounds into clinical trials and numerous drug approvals. Central to guiding the discovery process is to recognize active among non-active compounds. While large-scale computer simulations of compounds taken from a library (virtual screening) or designed de novo are highly desirable in the post-genomic area, many technical problems remain to be adequately addressed. This article presents an overview and discusses the limits of current computational methods for predicting the correct binding pose and accurate binding affinity. It also presents the performances of the most popular algorithms for exploring binary and multi-body protein interactions.     

Thermal Resonance at the Microscale in AC Scanning Thermal Microscopy with a Thermal-Resistive Probe

Investigation of the thermal-resistive probe response in an AC scanning thermal microscope (SThM) as a function of the distance probe–material surface under ambient conditions and the current excitation frequency is presented. The analysis of temperature experimental results points out a phenomenon which can be interpreted as a thermal wave resonance. The modeling of the thermal response with the finite element method considering the surrounding medium as a thermally conducting medium tends to confirm this. This phenomenon is independent of the sample nature and is related to the thermal diffusion length of the air medium between the probe and the sample. An equivalent resonance factor is defined: it shows a linear dependence with the characteristic distance for which the thermal resonance phenomenon is an extremum. The system—probe/sample surface—behaves as a resonant cavity at the microscale. This configuration is not specific to a SThM and can occur within electronic devices.     

Spring-in behavior of curved composites manufactured by Flexible Injection

This paper investigates the manufacturing distortion of curved composite parts manufactured by a new Liquid Composite Molding (LCM) process called Flexible Injection (FI). This technique uses a deformable tool to speed up the fabrication but may generate manufacturing defects when strongly curved shapes are processed. The goal of the study is to evaluate the impact of such heterogeneities on the dimensional stability of the product. Curved components were first manufactured with varying processing conditions to achieve a wide range of layup quality. The shape stability of the samples was then recorded as a function of temperature to measure the thermoelastic component of distortion and experimental results were compared with predictions made by two modeling techniques. Under certain conditions, manufacturing defects can significantly affect the distortion behavior. This suggests that a robust preforming procedure is of primary importance to produce curved parts by Flexible Injection with a high level of repeatability.     

Geometry modeling in cellular network planning

To design a cellular radio network (GSM, UMTS, WiFi …) it is indispensable today to use a radio planning software. In current commercialized tools, radio network planning is based on a numerical evaluation of a set of radio metrics, directly linked to quality of service notion, such as interference, throughput, coverage, capacity … The network configurations produced by such tools are generally faced with the human expert judgment who attaches great importance to the organizational aspects such as cells size and the topology. In other words, all those concepts related to the visual cells shape and geometry. In this article we emphasize the simplicity and the strength by which the geometrical concepts helps to bring out good network properties which are not taken into account by conventional radio criteria. On one hand, well-formed cells lead to reduce the number of handover calls, and to form transition zones between cells allowing proper completion of the handover procedure. On the other hand, cell geometry optimization produce performing network schemes in which the frequencies reuse (frequencies planning in GSM, WiFi) is simplified. We describe in this paper an original and practical modeling of the cellular geometry criteria granting the integration of this concept into the automatic planning process of mobile radio networks. The relevance of this criterion is assessed on three different levels. On a local level, we first establish the correlation between the geometric criteria and the improvement of point-by-point radio quality indicators. We secondly show geometry impact on radio frequency planning and the improving of the handover zones. Finally we analyze the impact of geometric criterion on improving indoor positioning systems.     

Predictive control of Timed Event Graphs with specifications defined by P-time Event Graphs

The aim of this paper is the predictive control of Timed Event Graphs with specifications defined by P-time Event Graphs. We propose a fixed-point approach which leads to a pseudo-polynomial algorithm. As the performance of the algorithm is crucial in on-line control, we highlight an important case where the resolution of this first algorithm is efficient. The second technique is a space controller on a horizon leading to a strongly polynomial algorithm.     

Computing the lowest equilibrium pose of a cable-suspended rigid body

We solve the problem of finding the lowest stable-equilibrium pose of a rigid body subjected to gravity and suspended in space by an arbitrary number of cables. Besides representing a contribution to fundamental rigid-body mechanics, this solution finds application in two areas of robotics research: underconstrained cable-driven parallel robots and cooperative towing. The proposed approach consists in globally minimizing the rigid-body potential energy. This is done by applying a branch-and-bound algorithm over the group of rotations, which is partitioned into boxes in the space of Euler-Rodrigues parameters. The lower bound on the objective is obtained through a semidefinite relaxation of the optimization problem, whereas the upper bound is obtained by solving the same problem for a fixed orientation. The resulting algorithm is applied to several examples drawn from the literature. The reported Matlab implementation converges to the lowest stable equilibrium pose generally in a few seconds for cable-robot applications. Interestingly, the proposed method is only mildly sensitive to the number of suspending cables, which is shown by solving an example with 1000 cables in two hours.     

On monitoring the process mean of autocorrelated observations with measurement errors using the w-of-w runs-rules scheme

Runs-rules have been widely used since the 1950s in industrial and nonindustrial process monitoring applications to improve the performance of basic and other traditional monitoring schemes. However, none of the studies on runs-rules have accounted for a process with a combined effect of measurement errors and autocorrelation. Hence, in this paper, the use of the w-of-w runs-rules to improve the performance of the Shewhart $\overline{X}$ scheme using an additive model with a constant variance and a first-order autoregressive model is proposed. To reduce the combined negative effect of measurement errors and autocorrelation, we implement a sampling strategy based on rational subgroups in which (a) multiple measurements per item are taken (instead of a standard single measurement) and (b) non-neighboring observations are gathered. Moreover, the latter sampling strategy is incorporated into the values of probability elements of a Markov chain matrix which is used to derive some closed-form expressions for the zero- and steady-state run-length distribution. The main finding of this study is that, with respect to some overall performance measures, the proposed scheme outperforms the existing Shewhart $\overline{X}$ scheme by a significant margin. A real-life example is used to illustrate the practical implementation of the proposed scheme.