A versatile planar QCM-based sensor design for nonlabeling biomolecule detection

Despite high theoretical sensitivity, low-cost manufacture, and compactness potentially amenable to lab-on-a-chip use, practical hurdles have stymied the application of the quartz crystal microbalance (QCM) for aqueous applications such as detection of biomolecular interactions. The chief difficulty lies in achieving a sufficiently stable resonance signal in the presence of even minute fluctuations in hydrostatic pressure. In this work, we present a novel versatile planar sensor chip design (QCM chip) for a microliter-scale on-line biosensor. By sealing the quartz resonator along its edges to a flat, solid support, we provide uniform support for the crystal face not exposed to solvent, greatly decreasing deformation of the crystal resonator under hydrostatic pressure. Furthermore, this cassette design obviates the need for direct handling when exchanging the delicate quartz crystal in the flow cell. A prototype 27-MHz sensor signal exhibited very low noise over a range of flow rates up to 100 microL/min. In contrast, signals obtained from a conventional QCM sensor employing an O-ring-based holder were less stable and deteriorated even further with increasing flow rate. Additional control designs with intermediate amounts of unsupported undersurface yielded intermediate levels of stability, consistent with the interpretation that deformation of the crystal resonator under fluctuating hydraulic pressure is the chief source of noise. As a practical demonstration of the design's high effective sensitivity, we readily detected interaction between myoglobin and surface-bound antibody.     

Fabrication of TiO2-based transparent conducting oxide on glass and polyimide substrates

We report on preparation and properties of anatase Nb-doped TiO₂ transparent conducting oxide films on glass and polyimide substrates. Amorphous Ti_0.96Nb_0.04O₂ films were deposited at room temperature by using sputtering, and were then crystallized through annealing under reducing atmosphere. Use of a seed layer substantially improved the crystallinity and resistivity (ρ) of the films. We attained ρ = 9.2 × 10^− 4 Ω cm and transmittance of ~ 70% in the visible region on glass by annealing at 300 °C in vacuum. The minimum ρ of 7.0 × 10^− 4 Ω cm was obtained by 400 °C annealing in pure H₂.     

Effect of Electron Correlation on Angular Dependence of Magnetoconductivity

We have measured the electrical resistivities and magnetoresistances (MR) of (EDT-DSDTFVO)₂X (X=FeCl₄, GaCl₄), where EDT-DSDTFVO stands for ethylenedithiodiselenadithiafulvalenothioquinone-1,3-dithiolemethide. These materials undergo gradual metal-insulator transitions at T_min=52 K for FeCl₄-salt and T_min=30 K for GaCl₄-salt, respectively. In spite of the similarity of the temperature dependence of the resistivity and its pressure effect, MR of both salts exhibit a clear contrast, i.e. FeCl₄-salt shows negative and GaCl₄, positive. Origin of the difference in the sign of MR between these salts are discussed in terms of the existence of π-d interaction.     

Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis

The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase β2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.     

Bone Tissue Engineering in Rat Calvarial Defects Using Induced Bone-like Tissue by rhBMPs from Immature Muscular Tissues In Vitro

This study aimed to induce bone-like tissue from immature muscular tissue (IMT) in vitro using commercially available recombinant human bone morphogenetic protein (rhBMP)-2, rhBMP-4, and rhBMP-7, and then implanting this tissue into a calvarial defect in rats to assess healing. IMTs were extracted from 20-day-old Sprague-Dawley (SD) fetal rats, placed on expanded polytetrafluoroethylene (ePTFE) with 10 ng/μL each of rhBMP-2, BMP-4, and BMP-7, and cultured for two weeks. The specimens were implanted into calvarial defects in 3-week-old SD rats for up to three weeks. Relatively strong radiopacity was observed on micro-CT two weeks after culture, and bone-like tissue, comprising osteoblastic cells and osteoids, was partially observed by H&E staining. Calcium, phosphorus, and oxygen were detected in the extracellular matrix using an electron probe micro analyzer, and X-ray diffraction patterns and Fourier transform infrared spectroscopy spectra of the specimen were found to have typical apatite crystal peaks and spectra, respectively. Furthermore, partial strong radiopacity and ossification were confirmed one week after implantation, and a dominant novel bone was observed after two weeks in the defect site. Thus, rhBMP-2, BMP-4, and BMP-7 differentiated IMT into bone-like tissue in vitro, and this induced bone-like tissue has ossification potential and promotes the healing of calvarial defects. Our results suggest that IMT is an effective tissue source for bone tissue engineering.     

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.     

Super-vector coding features extracted from both depth buffer and view-normal-angle images for part-based 3D shape retrieval

We have witnessed 3D shape models abundant in many application fields including 3D CAD/CAM, augmented/mixed reality (AR/MR), and entertainment. Creating 3D shape models from scratch is still very expensive. Efficient and accurate methods for shape retrieval is essential for 3D shape models to be reused. To retrieve similar 3D shape models, one must provide an arbitrary 3D shape as a query. Most of the research on 3D shape retrieval has been conducted with a “whole” shape as a query (aka whole-to-whole shape retrieval), while a “part” shape (aka part-to-whole shape retrieval) is more practically requested as a query especially by mechanical engineering with 3D CAD/CAM applications. A “part” shape is naturally constructed by a 3D range scanner as an input device. In this paper, we focus on the efficient method for part-to-whole shape retrieval where the “part” shape is assumed to be given by a 3D range scanner. Specifically, we propose a Super-Vector coding feature with SURF local features extracted from the View-Normal-Angle image, or the image synthesized by taking account of the angle between the view vector and the surface normal vector, together with the depth-buffered image, for part-to-whole shape retrieval. In addition, we propose a weighted whole-to-whole re-ranking method taking advantage of global information based on the result of part-to-whole shape retrieval. Through experiments we demonstrate that our proposed method outperforms the previous methods with or without re-ranking.     

Immunological Pathomechanisms of Spongiotic Dermatitis in Skin Lesions of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic pruritic skin disease with a complex pathogenesis underlying its heterogeneous clinical phenotypes and endotypes. The skin manifestation of AD reflects the cytokine milieu of a type-2-dominant immunity axis induced by genetic predisposition, innate immunity dysregulation, epidermal barrier defects, and allergic inflammation. However, the detailed pathomechanism of eczematous dermatitis, which is the principal characteristic of AD, remains unclear. This review examines previous studies demonstrating research progress in this area and considers the immunological pathomechanism of “spongiotic dermatitis”, which is the histopathological hallmark of eczematous dermatitis. Studies in this field have revealed the importance of IgE-mediated delayed-type hypersensitivity, the Fas/Fas-ligand system, and cell-mediated cytotoxicity in inducing the apoptosis of keratinocytes in spongiotic dermatitis. Recent studies have demonstrated that, together with infiltrating CD4 T cells, IgE-expressing dendritic cells (i.e., inflammatory dendritic epidermal cells and Langerhans cells) that capture specific allergens (i.e., house dust mites) are present in the spongiotic epidermis of lichenified eczema in patients with IgE-allergic AD. These findings suggest that IgE-mediated delayed-type hypersensitivity plays a pivotal role in the pathogenesis of spongiotic dermatitis in the skin lesions of AD.     

Experimental examination of the characteristics of bright-field scanning confocal electron microscopy images

We experimentally examined the characteristics of bright-field (BF) scanning confocal electron microscopy (SCEM) images by changing the observation conditions and comparing the images with those obtained by BF transmission electron microscopy (TEM) and BF scanning TEM (STEM) modes. The observation of 5-nm-diameter Au nanoparticles demonstrated that BF-SCEM produces object elongation of more than 2000?nm along the optical axis, as do BF-TEM and BF-STEM. We demonstrated the relationship between elongation length and geometric effects such as convergence and collection angles of a probe and the lateral size of an object; the relationship is consistent with previous theoretical prediction. Further, we observed interesting features that are seen only in the BF-SCEM images; the film contrast was strongly enhanced, compared with that of BF-STEM. In addition, a bright contrast appeared around the object position in the elongated images. Using this characteristic, we could determine the object position and structure.