Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development

The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.     

High-throughput detection and sizing of individual low-index nanoparticles and viruses for pathogen identification

Rapid, chip-scale, and cost-effective single particle detection of biological agents is of great importance to human health and national security. We report real-time, high-throughput detection and sizing of individual, low-index polystyrene nanoparticles and H1N1 virus. Our widefield, common path interferometer detects nanoparticles and viruses over a very large sensing area, orders of magnitude larger than competing techniques. We demonstrate nanoparticle detection and sizing down to 70 nm in diameter. We clearly size discriminate nanoparticles with diameters of 70, 100, 150, and 200 nm. We also demonstrate detection and size characterization of hundreds of individual H1N1 viruses in a single experiment.     

A hierarchical test methodology for systems on chip

We present a hierarchical test methodology for testing a SOC with heterogeneous cores, including the 1149.1-wrapped, P1500-wrapped, and BIST memory cores. We propose an 1149.1-based hierarchical test manager that also provides P1500 test control signals. This scheme includes a memory BIST interface, providing both serial and parallel access ports for BIST circuits. Our approach offers low area and pin overhead, and high flexibility     

A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.     

Neural-network-based variable structure control of electrohydraulicservosystems subject to huge uncertainties without persistent excitation

A novel scheme investigating a radial-basis-function neural network (RBFNN) with variable structure control (VSC) for electrohydraulic servosystems subject to huge uncertainties is presented. Although the VSC possesses some advantages (e.g., fast response, less sensitive to uncertainties, and easy implementation), the chattering control input often occurs. The reason for a chattering control input is that the switching control in the VSC is used to cope with the uncertainties. The larger the uncertainties which arise, the larger switching control occurs. In this paper, an RBFNN is employed to model the uncertainties caused by parameter variations, friction, external load, and controller. A new weight updating law using a revision of e-modification by a time varying dead zone can achieve an exponential stability without the assumption of persistent excitation for the uncertainties or radial basis function. Then, an RBFNN-based VSC is constructed such that some part of uncertainties are tackled, that the tracking performance is improved, and that the level of chattering control input is attenuated. Finally, the stability of the overall system is verified by the Lyapunov stability criterion     

Carbon Metabolism of a Soilborne Mn(II)-Oxidizing Escherichia coli Isolate Implicated as a Pronounced Modulator of Bacterial Mn Oxidation

Mn(II)-oxidizing microorganisms are generally considered the primary driving forces in the biological formation of Mn oxides. However, the mechanistic elucidation of the actuation and regulation of Mn oxidation in soilborne bacteria remains elusive. Here, we performed joint multiple gene-knockout analyses and comparative morphological and physiological determinations to characterize the influence of carbon metabolism on the Mn oxide deposit amount (MnODA) and the Mn oxide formation of a soilborne bacterium, Escherichia coli MB266. Different carbon source substances exhibited significantly varied effects on the MnODA of MB266. A total of 16 carbon metabolism-related genes with significant variant expression levels under Mn supplementation conditions were knocked out in the MB266 genome accordingly, but only little effect on the MnODA of each mutant strain was accounted for. However, a simultaneous four-gene-knockout mutant (namely, MB801) showed an overall remarkable MnODA reduction and an initially delayed Mn oxide formation compared with the wild-type MB266. The assays using scanning/transmission electron microscopy verified that MB801 exhibited not only a delayed Mn-oxide aggregate processing, but also relatively smaller microspherical agglomerations, and presented flocculent deposit Mn oxides compared with normal fibrous and crystalline Mn oxides formed by MB266. Moreover, the Mn oxide aggregate formation was highly related to the intracellular ROS level. Thus, this study demonstrates that carbon metabolism acts as a pronounced modulator of MnODA in MB266, which will provide new insights into the occurrence of Mn oxidation and Mn oxide formation by soilborne bacteria in habitats where Mn(II) naturally occurs.     

Improving Lipid Production of Yarrowia lipolytica by the Aldehyde Dehydrogenase-Mediated Furfural Detoxification

Yarrowia lipolytica, the non-conventional yeast capable of high lipogenesis, is a microbial chassis for producing lipid-based biofuels and chemicals from renewable resources such as lignocellulosic biomass. However, the low tolerance of Y. lipolytica against furfural, a major inhibitory furan aldehyde derived from the pretreatment processes of lignocellulosic biomass, has restricted the efficient conversion of lignocellulosic hydrolysates. In this study, the furfural tolerance of Y. lipolytica has been improved by supporting its endogenous detoxification mechanism. Specifically, the endogenous genes encoding the aldehyde dehydrogenase family proteins were overexpressed in Y. lipolytica to support the conversion of furfural to furoic acid. Among them, YALI0E15400p (FALDH2) has shown the highest conversion rate of furfural to furoic acid and resulted in two-fold increased cell growth and lipid production in the presence of 0.4 g/L of furfural. To our knowledge, this is the first report to identify the native furfural detoxification mechanism and increase furfural resistance through rational engineering in Y. lipolytica. Overall, these results will improve the potential of Y. lipolytica to produce lipids and other value-added chemicals from a carbon-neutral feedstock of lignocellulosic biomass.     

Multiparty quantum remote control

This paper proposes a multiparty quantum remote control protocol, which allows several controllers to perform various remote operations independently on a target state based on a shared entanglement of Greenberger–Home–Zeilinger state.     

Application of laser-induced breakdown spectroscopy for detecting leakage of boric acid

Recently, many studies have been conducted on developing on-line leak detection techniques in the reactor vessel head of nuclear power plants. One of them, laser-induced breakdown spectroscopy (LIBS), an effective technique of leak detection, which is a kind of atomic emission spectroscopy that uses a highly energetic laser pulse as the excitation source, has been of interest due to the fast and reliable identification of chemical elements for the precipitates formed by the leakage of cooling water containing boric acid. Experimental setup and tests were performed for the boric acid precipitates formed on the steel for various conditions with a Q-switched 532 nm Nd:YAG laser, optical lenses, an Echelle spectrograph and an intensified charge-coupled device detector. The LIBS system could be applied to obtain a spectral line (～249. 2 nm) corresponding to the atomic boron emission line for the precipitates of boric acid formed on low alloy steels, SA508 and SA533, as a substrate. The LIBS technique based on characterizing boric acid deposits might be used for detecting the leakage of cooling water in reactor vessel head of nuclear power plants.