Mechanism of Anti-Virulence Compound 187R Inhibiting Pseudomonas Aeruginosa Type III Secretion System

Antibiotics have been widely used for treating bacterial infectious diseases. However, the rapidly emerging of antibiotic resistance has dramatically decreased the efficacy of antibiotics and poses a serious worldwide crisis. In addition, the cell components serving as antibiotics’ targets are conserved in many different bacterial species, as a result, antibiotic treatments disrupt the host microbiota and negatively influence the hosts health condition. Therefore, new alternative strategies for fighting infectious diseases without causing antibiotic resistance and disturbing the host microbiota are needed. Type 3 secretion system (T3SS) is a highly conserved virulence factor presents in many different Gram-negative pathogens. It is required for pathogens such as P. aeruginosa, surviving and initiating infection in their hosts. Therefore, targeting the T3SS is a promising alternative strategy for developing new antimicrobial therapies without disrupting the hosts’ microbial community. Here, we identified a potent T3SS inhibitor, designated 187R, which strongly inhibits the expression of P. aeruginosa T3SS. Our data suggests that 187R inhibits T3SS expression through reducing the T3SS master regulator ExsA at the post-translational level. The impact of this anti-virulence compound on the hosts’ microbial community was also tested using Arabidopsis thaliana phyllosphere as a model. We demonstrates that compared to the traditional antibiotics, our T3SS inhibitor 187R can preserve the microbial community better than antibiotics

A spectral projection method for transmission eigenvalues

In this paper, we consider a nonlinear integral eigenvalue problem, which is a reformulation of the transmission eigenvalue problem arising in the inverse scattering theory. The boundary element method is employed for discretization, which leads to a generalized matrix eigenvalue problem. We propose a novel method based on the spectral projection. The method probes a given region on the complex plane using contour integrals and decides if the region contains eigenvalue(s) or not. It is particularly suitable to test if zero is an eigenvalue of the generalized eigenvalue problem, which in turn implies that the associated wavenumber is a transmission eigenvalue. Effectiveness and efficiency of the new method are demonstrated by numerical examples.Comment: The paper has been accepted for publication in SCIENCE CHINA Mathematic

A Phantom Study on Target Localization Accuracy Using Cone-Beam Computed Tomography

The purpose of this study is to evaluate the 3-dimensional target localization accuracy of cone-beam computed tomography (CBCT) using an on-board imager (OBI). An anthropomorphic pelvis phantom was used to simulate a range of offsets in the three translational directions and rotations around each of the three axes. After a translational or rotational offset was applied, a CBCT scan of the phantom was followed by image registration to detect the offsets in six degrees. The detected offsets were compared to the offset actually applied to give the detection error of the phantom position. Afterwards, the phantom was positioned by automatically moving the couch based on the detected offsets. A second CBCT scan followed by image registration was performed to give the residual error of the phantom positioning. On the average the detection errors and their standard deviations along the lateral, longitudinal and vertical axis are 0.3 ± 0.1, 0.3 ± 0.1 and 0.4 ± 0.1 mm respectively with respect to translational shifts ranging from 0 to 10 mm. The corresponding residual errors after positioning are 0.3 ± 0.1, 0.5 ± 0.1 and 0.3 ± 0.1 mm. For simulated rotational shifts ranging from 0 to 5 degrees, the average detection error and their standard deviation around lateral, longitudinal, and vertical axes are 0.1 ± 0.0, 0.2 ± 0.0, and 0.2 ± 0.0 degrees respectively. The residual errors after positioning are 0.4 ± 0.1, 0.6 ± 0.1, and 0.3 ± 0.1 mm along the lateral, longitudinal and vertical directions. These results indicate that target localization based on CBCT is capable of achieving sub-millimeter accuracy

Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis.

ObjectivesThiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 and thiamin transporter-2), and mitochondrial thiamin pyrophosphate transporter.DesignRandomized controlled study.SettingResearch laboratory at a Veterans Affairs Medical Center.SubjectsTwenty-four Sprague-Dawley rats were randomized into controls, mild, moderate, and severe sepsis with equal number of animals in each group.InterventionsSepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25%, 50%, and 75% of cecal length, defined as severe, moderate, and mild sepsis, respectively. Control animals underwent laparotomy only.Measurements and main resultsAfter 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [H]thiamin. Expressions of thiamin transporter-1, thiamin transporter-2, and mitochondrial thiamin pyrophosphate transporter proteins and messenger RNA were measured. Proinflammatory cytokines (interleukin-1β and interleukin-6) and adenosine triphosphate were also measured. Sepsis inhibited [H]thiamin uptake, and the inhibition was a function of sepsis severity. Both cell membrane thiamin transporters and mitochondrial thiamin pyrophosphate transporter expression levels were suppressed; also levels of adenosine triphosphate in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham-operated controls.ConclusionsFor the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion

Overview of compressed sensing: Sensing model, reconstruction algorithm, and its applications

With the development of intelligent networks such as the Internet of Things, network scales are becoming increasingly larger, and network environments increasingly complex, which brings a great challenge to network communication. The issues of energy-saving, transmission efficiency, and security were gradually highlighted. Compressed sensing (CS) helps to simultaneously solve those three problems in the communication of intelligent networks. In CS, fewer samples are required to reconstruct sparse or compressible signals, which breaks the restrict condition of a traditional Nyquist-Shannon sampling theorem. Here, we give an overview of recent CS studies, along the issues of sensing models, reconstruction algorithms, and their applications. First, we introduce several common sensing methods for CS, like sparse dictionary sensing, block-compressed sensing, and chaotic compressed sensing. We also present several state-of-the-art reconstruction algorithms of CS, including the convex optimization, greedy, and Bayesian algorithms. Lastly, we offer recommendation for broad CS applications, such as data compression, image processing, cryptography, and the reconstruction of complex networks. We discuss works related to CS technology and some CS essentials. © 2020 by the authors

Roles of B Cell-Intrinsic TLR Signals in Systemic Lupus Erythematosus

Toll-like receptors (TLRs) are a large family of pattern recognition receptors. TLR signals are involved in the pathogenesis of systemic lupus erythematosus. Mouse and human B cells constitutively express most TLRs. Many B cell subpopulations are highly responsive to certain TLR ligation, including B-1 B cells, transitional B cells, marginal zone B cells, germinal center B cell and memory B cells. The B cell-intrinsic TLR signals play critical roles during lupus process. In this review, roles of B cell-intrinsic TLR2, 4, 7, 8 and 9 signals are discussed during lupus pathogenesis in both mouse model and patients. Moreover, mechanisms underlying TLR ligation-triggered B cell activation and signaling pathways are highlighted.published_or_final_versio

CORE: Common Random Reconstruction for Distributed Optimization with Provable Low Communication Complexity

With distributed machine learning being a prominent technique for large-scale machine learning tasks, communication complexity has become a major bottleneck for speeding up training and scaling up machine numbers. In this paper, we propose a new technique named Common randOm REconstruction(CORE), which can be used to compress the information transmitted between machines in order to reduce communication complexity without other strict conditions. Especially, our technique CORE projects the vector-valued information to a low-dimensional one through common random vectors and reconstructs the information with the same random noises after communication. We apply CORE to two distributed tasks, respectively convex optimization on linear models and generic non-convex optimization, and design new distributed algorithms, which achieve provably lower communication complexities. For example, we show for linear models CORE-based algorithm can encode the gradient vector to $\mathcal{O}(1)$-bits (against $\mathcal{O}(d)$), with the convergence rate not worse, preceding the existing results