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Manufacture of chimeric antigen receptor (CAR)‐T cells usually involves the use of viral delivery systems to achieve high transgene expression. However, it can be costly and may result in random integration of the CAR into the genome, creating several disadvantages including variation in transgene expression, functional gene silencing and potential oncogenic transformation. Here, we optimized the method of nonviral, CRISPR/Cas9 genome editing using large donor DNA delivery, knocked‐in an anti‐tumor single chain variable fragment (scFv) into the N‐terminus of CD3ε and efficiently generated fusion protein (FP) T cells. These cells displayed FP integration within the TCR/CD3 complex, lower variability in gene expression compared to CAR‐T cells and good cell expansion after transfection. CD3ε FP T cells were predominantly CD8+ effector memory T cells, and exhibited anti‐tumor activity in vitro and in vivo. Dual targeting FP T cells were also generated through the incorporation of scFvs into other CD3 subunits and CD28. Compared to viral‐based methods, this method serves as an alternative and versatile way of generating T cells with tumor‐targeting receptors for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Recent studies on osteosarcoma regimens have mainly focused on modifying the combination of antineoplastic agents rather than enhancing the therapeutic efficacy of each component. Here, an albumin nanocluster (NC)‐assisted methotrexate (MTX), doxorubicin (DOX), and cisplatin (MAP) regimen with improved antitumor efficacy is presented. Human serum albumin (HSA) is decorated with thiamine pyrophosphate (TPP) to increase the affinity to the bone tumor microenvironment (TME). MTX or DOX (hydrophobic MAP components) is adsorbed to HSA‐TPP via hydrophobic interactions. MTX‐ or DOX‐adsorbed HSA‐TPP NCs exhibit 20.8‐ and 1.64‐fold higher binding affinity to hydroxyapatite, respectively, than corresponding HSA NCs, suggesting improved targeting ability to the bone TME via TPP decoration. A modified MAP regimen consisting of MTX‐ or DOX‐adsorbed HSA‐TPP NCs and free cisplatin displays a higher synergistic anticancer effect in HOS/MNNG human osteosarcoma cells than conventional MAP. TPP‐decorated NCs show 1.53‐fold higher tumor accumulation than unmodified NCs in an orthotopic osteosarcoma mouse model, indicating increased bone tumor distribution. As a result, the modified regimen more significantly suppresses tumor growth in vivo than solution‐based conventional MAP, suggesting that HSA‐TPP NC‐assisted MAP may be a promising strategy for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Rivaroxaban (RIV; Xarelto; Janssen Pharmaceuticals, Beerse, Belgium) is one of the direct oral anticoagulants. The drug is a strong substrate of cytochrome P450 (CYP) enzymes and efflux transporters. This study aimed to develop a physiologically‐based pharmacokinetic (PBPK) model for RIV. It contained three hepatic metabolizing enzyme reactions (CYP3A4, CYP2J2, and CYP‐independent) and two active transporter‐mediated transfers (P‐gp and BCRP transporters). To illustrate the performance of the developed RIV PBPK model on the prediction of drug–drug interactions (DDIs), carbamazepine (CBZ) was selected as a case study due to the high DDI potential. Our study results showed that CBZ significantly reduces the exposure of RIV. The area under the concentration‐time curve from zero to infinity (AUCinf) of RIV was reduced by 35.2% (from 2221.3 to 1438.7 ng*h/ml) and by 25.5% (from 2467.3 to 1838.4 ng*h/ml) after the first dose and at the steady‐state, respectively, whereas the maximum plasma concentration (Cmax) of RIV was reduced by 37.7% (from 266.3 to 166.1 ng/ml) and 36.4% (from 282.3 to 179.5 ng/ml), respectively. The developed PBPK model of RIV could be paired with PBPK models of other interested perpetrators to predict DDI profiles. Further studies investigating the extent of DDI between CBZ and RIV should be conducted in humans to gain a full understanding of their safety and effects. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the association between the use of interdental cleaning devices and proximal caries experience. Methods: This study used a cross‐sectional data from the Sixth Korea National Health and Nutrition Examination Survey (2013‐2015). A total of 13 525 adults aged 19‐64 years who participated in both the nutrition survey and the health examination survey were included. Data on sociodemographic factors (age and sex), socioeconomic factors (level of education and household income) and personal health practices (frequency of toothbrushing, visits to dental clinic, frequency of snacking and self‐rated oral health status), and number of proximal caries were collected. Prevalence ratios (PRs) and 95% confidence intervals (95% CI) were calculated using the multivariable Poisson generalized linear model according to use of dental floss or an interdental brush. The risk of proximal caries for dental floss following the stratification of participants into various subgroups related to oral health was assessed. Results: While nonflossers had 1.46 times (PR 1.46, 95% CI: 1.16‐1.84) higher risk for proximal caries than flossers, the use of an interdental brush was not associated with proximal caries. In the nonflossers, the association for proximal caries was the strongest in those in their 40s (PR 2.28, 95% CI: 1.29‐4.03), followed by those in their 30s (PR 1.85, 95% CI: 1.18‐2.90). Although nonflossers with middle‐low household income had a 59% higher risk (PR 1.59, 95% CI: 1.24‐2.03) for proximal caries than those with high household income, there were no significant differences in household income in flossers. Conclusions: The findings of the study suggest that flossing at home along with toothbrushing is one of the easiest ways to prevent proximal caries. Therefore, dental floss should not be excluded from oral healthcare products. [ABSTRACT FROM AUTHOR]

The surface of fumed nano‐silica (nano‐SiO2) was treated with an alkyl silazane to change from hydrophilic surface to hydrophobic, and the surface of aluminum trihydroxide (nano‐ATH) was treated with a vinyl silazane to improve electrical properties (high voltage direct current [HVDC] breakdown strength and tracking resistance) in silicone nanocomposites. They were prepared by mixing liquid silicone resin with the modified nano‐SiO2 and the modified nano‐ATH, and the effects of the modified nano‐ATH particles on the electrical properties were studied in order to apply them to heavy electric equipment. The surface modifications were confirmed by thermogravimetric analysis and contact angle analysis. As the nano‐ATH content increased, (±)HVDC breakdown strength increased and tracking resistance was greatly improved. As the nano‐ATH content increased, the initial generation of leakage current was delayed, and the occurrence frequency and the intensity of the leakage current decreased. The erosion weight due to the tracking also decreased. [ABSTRACT FROM AUTHOR]

Objective: The objective of this case/non‐case study was to detect rebamipide‐related pulmonary adverse events (AE) compared with other drugs for acid‐related disorders based on population‐level data. Methods: From 2009 to 2018, AE reports on drugs for acid‐related disorders, which are anatomical therapeutic chemical code A02B drugs, in the Korea Adverse Events Reporting System (KAERS) database were examined. The reporting odds ratio (ROR) was calculated, and the odds of reporting pulmonary AE for rebamipide and all other A02B drugs were compared. Furthermore, a stratified analysis according to patients' age and sex was conducted. Results: Altogether 13 (0.05%) and 157 (0.11%) cases of pulmonary AE were reported for rebamipide and all other A02B drugs, respectively. The risk of reporting pulmonary AE was significantly lower for rebamipide than for all other A02B drugs (ROR 0.49, 95% confidence interval [CI] 0.28–0.87). The number of reports of pulmonary AE for rebamipide was significantly higher among patients aged ≥65 years than those aged <65 years (ROR 19.36, 95% CI 2.50–149.97). Conclusions: Rebamipide was less often reported for pulmonary AE. However, healthcare professionals need to be aware of the risk of pulmonary AE in elderly patients. [ABSTRACT FROM AUTHOR]

This paper theoretically and empirically explores the reliability gain that can be obtained by installing multiple antennas in on‐vehicle broadcasting receivers. Analytical derivations reveal that maximal‐ratio‐combining‐based diversity allows a multi‐antenna receiver (MR) to achieve significantly better coverage probability than a single‐antenna receiver (SR). In particular, the notable MR gains for low‐power reception and high‐throughput services are highlighted. We also discuss various aspects of mobile MRs, including geometric coverage, volume of the users served, and impact of receiver velocity. To examine the feasibility of MRs in the real world, extensive field experiments were conducted, particularly with on‐air ATSC 3.0 broadcast transmissions. Relying on the celebrated erroneous second ratio criterion, MRs with two and four antennas were verified to achieve notable reliability gains over SRs in practice. Furthermore, our results also prove that layered‐division multiplexing can cope better with receiver mobility than traditional time‐division multiplexing when multiple services are intended in the same radio frequency channel. [ABSTRACT FROM AUTHOR]

To develop silicone/nanosilica insulation materials for high voltage direct current (HVDC), hydrophilic surface of fumed nanosilica was changed to hydrophobic by modifying with various ratios of alkylsilane and alkylsilane/vinylsilane coupling agents and the effects of the modified nanosilicas on the HVDC breakdown strength under negative or positive polarities were studied. Dielectric and tensile properties were also studied. The surface modification was confirmed by Fourier‐transform infrared spectroscopy (FT‐IR) analysis and the weights of the alkyl and alkyl/vinyl groups on the modified nanosilicas were measured by thermogravimetric analysis (TGA). Silicone rubber nanocomposites were prepared by mixing a liquid silicone rubber (LSR) and the modified nanosilicas, in which the mixing ratio of the LSR to the nanosilicas was fixed to be 20 wt%. Transmission electron microscopy (TEM) was used to observe the even dispersion of the nanosilica particles in the LSR matrix, and it was found that the surface‐modified nanosilicas were well dispersed in the form of nano‐clusters with 20–60 nm in size. Electrical properties (±HVDC breakdown strength and dielectric properties) and mechanical properties (tensile strength and elongation‐at‐break) were estimated, and it was found that ±HVDC breakdown strength and tensile strength were maximal when the surface modification ratio of alkyl: alkyl/vinyl groups was 50: 50 wt%. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin‐methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1‐ and 1.4‐fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro‐conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration. [ABSTRACT FROM AUTHOR]

Abstract: BN 2‐vinylnaphthalene, a BN aromatic vinyl monomer, is copolymerized with styrene under free radical conditions. Oxidation yields styrene–vinyl alcohol (SVA) statistical copolymers with tunable hydroxy group content. Comprehensive spectroscopic investigation provides proof of structure. Physical properties that vary systematically with hydroxy content include solubility and glass transition temperature. BN aromatic polymers represent a platform for the preparation of diverse functional polymeric architectures via the remarkable reaction chemistry of C−B bonds. [ABSTRACT FROM AUTHOR]

Coupling between iso(thio)cyanates and amines, alcohols, and thiols to yield (thio)urea/urethane in the gas phase is important for the vacuum deposition processes of functional organic thin films such as molecular layer deposition or chemical vapor deposition. In this study, the kinetics and thermodynamics of 12 reactions between bifunctional reactants containing NCO/NCS and NH2/OH/SH moieties were calculated using double-hybrid density functional theory to find systematic structure-reactivity relationships. The activation energy for the proton-transfer step was correlated with the basicity of the nucleophile/Brønsted acid reactants, while the exothermicity of the coupling reaction depends on whether the other functionality is NCO or NCS. Analysis of the transition states revealed that the location of the transition state is affected by the basicity of the reactants. Vibrational and electronic spectra of the product were obtained to help future experimental investigations. [ABSTRACT FROM AUTHOR]

NOD-like receptor family protein 3 (NLRP3)-mediated inflammasome activation promotes caspase-1-dependent production of interleukin-1β ( IL-1β) and requires the adaptor protein ASC. Compared with the priming and activation mechanisms of the inflammasome signaling pathway, post-translational ubiquitination/deubiquitination mechanisms controlling inflammasome activation have not been clearly addressed. We here demonstrate that the deubiquitinating enzyme USP50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63-linked polyubiquitination of ASC. USP50 knockdown in human THP-1 cells and mouse bone marrow-derived macrophages shows a significant decrease in procaspase-1 cleavage, resulting in a reduced secretion of IL-1β and interleukin-18 ( IL-18) upon treatment with NLRP3 stimuli and a reduction in ASC speck formation and oligomerization. Thus, we elucidate a novel regulatory mechanism of the inflammasome signaling pathway mediated by the USP50 deubiquitinating enzyme. [ABSTRACT FROM AUTHOR]

A helical rod-coil motif was employed to design water-soluble peptoid amphiphiles. Prior to this study, this approach was rarely exploited in the construction of amphiphilic peptoids. The helical rod-coil motif enabled complete dissolution of the peptoids 1 and 2 in water. The critical micelle concentration ( CMC) of the water-soluble peptoids was measured. Circular dichroism ( CD) analysis of each peptoid was performed to confirm the helical secondary structure in solution. Scanning electron microscopy ( SEM) revealed the surface morphology of the self-assembled peptoid structures. Water-soluble peptoids comprised helical rod-coil structures provide a variety of self-assembled architectures in aqueous solutions. [ABSTRACT FROM AUTHOR]

Recently, development of biocompatibility functional cosmetic agents as antioxidant or whitening agent has increased. In this study, synthetic cysteine derivatives ( DBLS-21, -24, and -33) were developed containing syringic acid and cysteine moieties ( l-cysteine ethyl ester, N-acetyl cysteine methyl ester, and N-acetyl cysteine ethyl ester), and their antioxidative and whitening activities were evaluated. The cellular protective effect (τ50) of DBLS-21 was 51.1 min at 50 μM on 1O2 -induced hemolysis of erythrocytes. This activity was slightly higher than that of α-tocopherol (43.6 min) as a lipophilic antioxidant. In the melanogenesis inhibitory effect, DBLS-21, -24, and -33 was 1.6-, 1.8-, and 2.5-fold higher than arbutin, respectively. In particular, DBLS-21 and -33 was 112.8- and 6.1-fold higher than arbutin, respectively (293.4 μM) on tyrosinase inhibition activity ( IC50 ). But DBLS-24 had no tyrosinase inhibitory activity. These results suggest that cysteine derivatives possess potential for use as an antioxidant agent ( DBLS-21) and whitening agents (all derivatives) in cosmetics. [ABSTRACT FROM AUTHOR]

Alantolactone (ALA) is a major bioactive sesquiterpene lactone present in the roots of Inula helenium L. (Asteraceae) which has been used widely in traditional medicine against various diseases such as asthma, cancer and tuberculosis. The pharmacologic activities of alantolactone have been well characterized, yet information on the physicochemical and pharmacokinetic properties of alantolactone and their mechanistic elucidation are still limited. Thus, this study aims to investigate the oral absorption and disposition of alantolactone and their relevant mechanisms. Log P values of alantolactone ranged from 1.52 to 1.84, and alantolactone was unstable in biological samples such as plasma, urine, bile, rat liver microsomes (RLM) and simulated gastrointestinal fluids. The metabolic rate of alantolactone was markedly higher in rat liver homogenates than in the other tissue homogenates. A saturable and concentration-dependent metabolic rate profile of alantolactone was observed in RLM, and rat cytochrome P450 (CYP) 1 A, 2C, 2D and 3 A subfamilies were significantly involved in its hepatic metabolism. Based on the well-stirred model, the hepatic extraction ratio (HER) was estimated to be 0.890-0.933, classifying alantolactone as a drug with high HER. Moreover, high total body clearance (111 ± 41 ml/min/kg) and low oral bioavailability (0.323%) of alantolactone were observed in rats. Taken together, the present study demonstrates that the extensive hepatic metabolism, at least partially mediated by CYP, is primarily responsible for the high total body clearance of alantolactone, and that the low oral bioavailability of alantolactone could be attributed to its low stability in gastrointestinal fluids and a hepatic first-pass effect in rats. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper introduces a new approach to teaching and learning finite element behavior through the interactive simulation of eigenmodes, using a finite element analysis program with functions specialized for this purpose. The eigenvalues and eigenvectors of the stiffness matrix are interpreted in terms of displacement and strain energy modes representing the basic characteristics of an element or an assembly of elements. The eigenmode simulation progresses in connection with actual finite element analysis. The eigenmodes and corresponding model behaviors are simultaneously visualized. Thus, the implication of eigenmodes in the model behaviors can be perceived in association with the practical application of the finite element method. The visualization is updated instantly in response to the change of model type, element order, integration rule, and boundary constraints, etc. Such interactivity is an essential feature of the simulation process for the experimental study of eigenmodes and associated model behaviors. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:872-886, 2015; View this article online at wiley ; DOI [ABSTRACT FROM AUTHOR]

Phenylboronic acid-functionalized chondroitin sulfate A (CSA)-deoxycholic-acid (DOCA)-based nanoparticles (NPs) are prepared for tumor targeting and penetration. (3-Aminomethylphenyl)boronic acid (AMPB) is conjugated to CSA-DOCA conjugate via amide bond formation, and its successful synthesis is confirmed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Doxorubicin (DOX)-loaded CSA-DOCA-AMPB NPs with a mean diameter of ≈200 nm, a narrow size distribution, negative zeta potential, and spherical morphology are prepared. DOX release from NPs is enhanced at acidic pH compared to physiological pH. CSA-DOCA-AMPB NPs exhibit improved cellular uptake in A549 (human lung adenocarcinoma) cells and penetration into A549 multicellular spheroids compared to CSA-DOCA NPs as evidenced by confocal laser scanning microscopy and flow cytometry. In vivo tumor targeting and penetrating by CSA-DOCA-AMPB NPs, based on both CSA-CD44 receptor and boronic acid-sialic acid interactions, is revealed using near-infrared fluorescence (NIRF) imaging. Penetration of NPs to the core of the tumor mass is observed in an A549 tumor xenografted mouse model and verified by three-dimensional NIRF imaging. Multiple intravenous injections of DOX-loaded CSA-DOCA-AMPB NPs efficiently inhibit the growth of A549 tumor in the xenografted mouse model and increase apoptosis. These boronic acid-rich NPs are promising candidates for cancer therapy and imaging. [ABSTRACT FROM AUTHOR]

We have previously reported that Smad6, one of the inhibitory Smads of transforming growth factor-β ( TGF-β)/bone morphogenetic protein ( BMP) signaling, inhibits Toll-like receptor ( TLR) 4 signaling by disrupting the Pellino-1-mediated TLR4 signaling complex. Here, we developed Smaducin-6, a novel membrane-tethered palmitic acid-conjugated Smad6-derived peptide composed of amino acids 422-441 of Smad6. Smaducin-6 interacted with Pellino-1, located in the inner membrane, thereby disrupting the formation of IRAK1-, RIP1-, IKKε-mediated TLR4 signaling complexes. Systemic administration of Smaducin-6 showed a significant therapeutic effect on mouse TLR4-mediated inflammatory disease models, cecal-ligation-puncture ( CLP)-induced sepsis, and lipopolysaccharide-induced endotoxemia, by inhibiting pro-inflammatory cytokine production and apoptosis while enhancing neutrophil migration and bacterial clearance. Our findings provide clues to develop new peptide-based drugs to target Pellino-1 protein in TLR4 signaling pathway for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

This article introduces the educational functions of a computer program developed and put into practice for the computer-aided instruction of the finite element method. An interactive simulation with graphical visualization is used as a tool to teach and learn the concepts and procedures related to the construction and solution of finite element stiffness equations. The tool encompasses the stages of processing finite element equations from element modeling to equation solving. Any operation of this educational tool is not an emulation of computational processes, but an actual execution of finite element processing. Thus, instructors of the finite element method may use this educational program as a tool to present complex computational aspects in comprehensible graphic images. Students may experience and explore each stage of the computation using the interactive simulation, and attain a better understanding of the concepts and procedures of the stiffness method, bypassing manual calculation or computer programming. The instructional tool has been implemented as a part of a finite element analysis program. © 2013 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:157-169, 2015; View this article online at ; DOI [ABSTRACT FROM AUTHOR]

The arginine repressor (ArgR) is a transcriptional regulator which regulates genes encoding proteins involved in arginine biosynthesis and the arginine catabolic pathway. ArgR from the alkaliphilic bacterium Bacillus halodurans was cloned and overexpressed in Escherichia coli. ArgR (Bh2777) from B. halodurans is composed of 149 amino-acid residues with a molecular mass of 16 836 Da. ArgR was crystallized at 296 K using 1,2-propanediol as a precipitant. Crystals of N-terminally His-tagged ArgR were obtained by the sitting-drop vapour-diffusion method. Dehydrated crystals showed a dramatic improvement in diffraction quality and diffracted to 2.35 Å resolution. The crystals belonged to the cubic space group I23, with unit-cell parameters a = b = c = 104.68 Å. The asymmetric unit contained one monomer of ArgR, which generates a trimer by the threefold axis of the space group, giving a crystal volume per mass ( VM) of 2.98 Å3 Da−1 and a solvent content of 56.8%. [ABSTRACT FROM AUTHOR]

Purpose: Registration between 2D ultrasound (US) and 3D preoperative magnetic resonance (MR) (or computed tomography, CT) images has been studied recently for US-guided intervention. However, the existing techniques have some limits, either in the registration speed or the performance. The purpose of this work is to develop a real-time and fully automatic registration system between two intermodal images of the liver, and subsequently an indirect lesion positioning/tracking algorithm based on the registration result, for image-guided interventions. Methods: The proposed position tracking system consists of three stages. In the preoperative stage, the authors acquire several 3D preoperative MR (or CT) images at different respiratory phases. Based on the transformations obtained from nonrigid registration of the acquired 3D images, they then generate a 4D preoperative image along the respiratory phase. In the intraoperative preparatory stage, they properly attach a 3D US transducer to the patient's body and fix its pose using a holding mechanism. They then acquire a couple of respiratory-controlled 3D US images. Via the rigid registration of these US images to the 3D preoperative images in the 4D image, the pose information of the fixed-pose 3D US transducer is determined with respect to the preoperative image coordinates. As feature(s) to use for the rigid registration, they may choose either internal liver vessels or the inferior vena cava. Since the latter is especially useful in patients with a diffuse liver disease, the authors newly propose using it. In the intraoperative real-time stage, they acquire 2D US images in real-time from the fixed-pose transducer. For each US image, they select candidates for its corresponding 2D preoperative slice from the 4D preoperative MR (or CT) image, based on the predetermined pose information of the transducer. The correct corresponding image is then found among those candidates via real-time 2D registration based on a gradient-based similarity measure. Finally, if needed, they obtain the position information of the liver lesion using the 3D preoperative image to which the registered 2D preoperative slice belongs. Results: The proposed method was applied to 23 clinical datasets and quantitative evaluations were conducted. With the exception of one clinical dataset that included US images of extremely low quality, 22 datasets of various liver status were successfully applied in the evaluation. Experimental results showed that the registration error between the anatomical features of US and preoperative MR images is less than 3 mm on average. The lesion tracking error was also found to be less than 5 mm at maximum. Conclusions: A new system has been proposed for real-time registration between 2D US and successive multiple 3D preoperative MR/CT images of the liver and was applied for indirect lesion tracking for image-guided intervention. The system is fully automatic and robust even with images that had low quality due to patient status. Through visual examinations and quantitative evaluations, it was verified that the proposed system can provide high lesion tracking accuracy as well as high registration accuracy, at performance levels which were acceptable for various clinical applications. [ABSTRACT FROM AUTHOR]

Instructional tools for the computer-aided education of structural analysis have been implemented as an extension of a finite element analysis program, VisualFEA. They are devised to promote understanding in structural analysis, and stimulate interest in the subject by substantiating the conceptual principles and visually exhibiting the complex computational processes with the aid of interactive computer graphics. In lieu of manipulation with pre-supplied conditions or the input of assumed data, the instructional tools are operated through a real and practical process of structural analysis from the creation of modeling data to the presentation of solution results. The basic principles, computing formulae, and methods of analysis in structural mechanics are simulated for instructional purposes on the basis of finite element technology. VisualFEA has a number of educational functions for use in teaching and learning structural analysis. Among them, only those related to frame analysis are introduced in this article. There are numerous programs for frame analysis. However, the educational features described in this article are not common in any other programs for similar purposes. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:387-409, 2014; View this article online at ; DOI [ABSTRACT FROM AUTHOR]

This article introduces a computer program for computer-aided education about Mohr's circle and its practical use. The instructional tool has been implemented as part of a finite element analysis program, VisualFEA. The proposed approach to teaching and learning Mohr's circle is distinguished from previous work by its association with practical analysis models. The Mohr's circle is displayed and operated on the basis of stress data obtained from finite element analysis whereas arbitrarily assumed numerical values are used in other programs. The analysis can be extended to elasto-plastic models with various yield criteria. Thus, the program can be regarded not only as an instructional module for studying Mohr's circle itself, but also as a training tool for exercising its practical application. This article describes the characteristics of the program's educational features and suggests important points for teaching and learning Mohr's circle and related subjects using VisualFEA. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:494-508, 2014; View this article online at ; DOI [ABSTRACT FROM AUTHOR]

Aim The problems of youth social withdrawal (or hikikomori) became a hot-button social issue in Japan in the 1990s. Unfortunately, current nosology in the DSM-IV may not adequately capture the concept of socially withdrawn youth ( SWY) or hikikomori. This study aimed to investigate core SWY issues, evaluate SWY's psychopathologies, and approach them therapeutically through a home visitation program. Methods Participants were 65 youth referred by community mental health centers and psychiatric clinics around Seoul and Kyongki- Do province. Among them, only 41 participants (31 male, 10 female, mean age 15 ± 3.6 years) fit our SWY criteria. In addition, 248 middle and high school students in Seoul were recruited as a baseline control group. Caseworkers interviewed the SWY participants and their parents in their homes, using our structured interview manual and a number of psychiatric scales. Caseworkers also approached the participants therapeutically. Results Participants' Depression Inventory, Trait Anxiety Inventory, Social Anxiety Scale, and Internet Addiction Scale scores were significantly higher than those of baseline controls. Participants' mean number of psychotherapeutic sessions was 2.8, and the mean number of parental interview sessions was 3.4. After the therapeutic sessions, Global Assessment Functioning scores and social activities had improved somewhat in 68.3% of participants. Conclusion These findings suggest that SWY is a complex phenomenon, so an individual psychopathologic process is very important for treatment. The most difficult problem in SWY treatment was therapeutic access. Hence, the home visit approach with a structured manual may be a good gateway for solving this problem. [ABSTRACT FROM AUTHOR]

Difficulty in the treatment of tuberculosis and growing drug resistance in Mycobacterium tuberculosis ( Mtb) are a global health issue. Carbapenems inactivate L,D-transpeptidases; meropenem, when administered with clavulanate, showed in vivo activity against extensively drug-resistant Mtb strains. LdtMt2 (Rv2518c), one of two functional L,D-transpeptidases in Mtb, is predominantly expressed over LdtMt1 (Rv0116c). Here, the crystal structure of N-terminally truncated LdtMt2 (residues Leu131-Ala408) is reported in both ligand-free and meropenem-bound forms. The structure of meropenem-inhibited LdtMt2 provides a detailed structural view of the interactions between a carbapenem drug and Mtb L,D-transpeptidase. The structures revealed that the catalytic L,D-transpeptidase domain of LdtMt2 is preceded by a bacterial immunogloblin-like Big_5 domain and is followed by an extended C-terminal tail that interacts with both domains. Furthermore, it is shown using mass analyses that meropenem acts as a suicide inhibitor of LdtMt2. Upon acylation of the catalytic Cys354 by meropenem, the `active-site lid' undergoes a large conformational change to partially cover the active site so that the bound meropenem is accessible to the bulk solvent via three narrow paths. This work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antituberculosis drugs against drug-resistant Mtb. [ABSTRACT FROM AUTHOR]

Abstract: Pyrococcus furiosus PF2050 is an uncharacterized putative protein that contains two DUF2666 domains. Functional and structural studies of PF2050 have not previously been performed. In this study, we determined the crystal structure of PF2050. The structure of PF2050 showed that the two DUF2666 domains interact tightly, forming a globular structure. Each DUF2666 domain comprises an antiparallel β-sheet and an α-helical bundle. One side of the PF2050 structure has a positively charged basic cleft, which may have a DNA-binding function. Furthermore, we confirmed that PF2050 interacts with circular and linear dsDNA. [Copyright &y& Elsevier]

A 2.4-GHz bandpass filter is implemented on a flexible printed circuit board with a thickness of 127 μm for wearable RF applications.The bandpass filter is realized in a double-sided structure, of which the top side provides the main filtering characteristics using two coupled resonators and the bottom side provides efficient signal feeding and coupling using mixed coupling scheme. The mixed coupling scheme combining the broadside- and cross-coupling structures is advantageous to improve the insertion loss. The filter characteristics when bended by up to 90° are simulated using a three-dimensional electromagnetic simulation tool and experimentally verified. Measurement results show that the insertion loss is less than 1 dB and the return loss is less than 26 dB across the total passband from 2.4 to 2.5 GHz. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 54:384-387, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26588 [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV-related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV-related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan-Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow-up duration was 28.9 months (range, 12.0-57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg-negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg-negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV-related HCC. [ABSTRACT FROM AUTHOR]

A broadband suspended substrate filter is proposed and implemented using dual-mode resonator aiming at transmitting the signals in the passband of 10-18 GHz. It is composed of two quarter-wavelength resonators and inductor. The inductor is a short-circuited stub. After optimization of this filter, a good bandpass behavior with 10 transmission poles is theoretically realized and experimentally confirmed. Within the whole BPF passband, the return loss is found better than 10 dB, and the insertion loss is less than 1.9 dB. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26070 [ABSTRACT FROM AUTHOR]

High glucose levels induce cell death in many cell types, including pancreatic β-cells. Although protective agents against glucotoxicity have been searched for extensively, so far none have been found. In this report, we tested silk fibroin (SF) as a candidate material for antiglucotoxicity in the pancreatic β-cell (HIT-T15 cell) line. Approximately 50% of cells were killed after treatment with 80 mg/mL glucose. This reduction of cell number was recovered by the addition of SF at 50 mg/mL. SF treatment also decreased cellular reactive oxygen species (ROS) and increased proliferating cellular nuclear antigen (PCNA) immunoreactivity. In addition, TUNEL assays demonstrated that SF protects against glucose-induced apoptosis of HIT-T15 cells, suggesting that SF might protect cells from cell death by lowering cellular ROS levels. SF also induced expression of the insulin-like growth factor-1 (IGF-1) gene, and IGF-1 expression may be the cause of SF-induced protection against glucose toxicity. Taken together, these results suggest that SF could serve as a potential therapeutic agent to treat the hyperglycemia-induced death of pancreatic β-cells. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:238-243, 2011; View this article online at . DOI 10.1002/jbt.20381 [ABSTRACT FROM AUTHOR]

In this letter, we present the 2 by 1 and 2 by 2 array microstrip patch antennas using the waveguide endwall coupler at 24 GHz. These antennas consist of a waveguide feed and two or four patches that are excited by the endwall coupler. As the measured results, the 2 by 2 array antenna has the gain of 10.7 dBi and the bandwidth of 1.3 GHz, and half power beamwidth is 31° on the E-plane and 35° on the H-plane. Because this transition technique is very simple and easy to fabricate, it can be used for low cost and high volume production for commercial millimeter-wave applications. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:630-633, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.25794 [ABSTRACT FROM AUTHOR]

Purpose To compare gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) with gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI in preoperative living liver donors for the evaluation of vascular and biliary variations. Materials and Methods Sixty-two living liver donors who underwent preoperative MRI were included in this study. Thirty-one patients underwent MRI with Gd-EOB-DTPA enhancement, and the other 31 underwent MRI with Gd-BOPTA enhancement. Two abdominal radiologists retrospectively reviewed dynamic T1-weighted and T1-weighted MR cholangiography images and ranked overall image qualities for the depiction of the hepatic artery, portal vein, hepatic vein, and bile duct on a 5-point scale and determined the presence and types of normal variations in each dynamic phase. Semiquantitative analysis for bile duct visualization was also conducted by calculating bile duct-to-liver contrast ratios. Results No statistical differences were found between the two contrast media in terms of hepatic artery or bile duct image quality by the two reviewers, or in terms of portal vein image quality by one reviewer ( P > 0.05). Gd-BOPTA provided better image qualities than Gd-EOB-DTPA for the depiction of hepatic veins by both reviewers, and for the depiction of portal veins by one reviewer ( P < 0.01). The two contrast media-enhanced images had similar bile duct-to-liver contrast ratios ( P > 0.05). Regarding diagnostic accuracies with hepatic vascular/biliary branching types, no significant differences were observed between the two contrast media ( P > 0.05). Conclusion Gd-EOB-DTPA could be as useful as Gd-BOPTA for the preoperative evaluation of living liver donors, and has the advantage of early hepatobiliary phase image acquisition. J. Magn. Reson. Imaging 2011;33:149-159. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To retrospectively evaluate the MR imaging features of early bile duct cancer and to correlate them with the clinicopathologic findings. Materials and Methods This retrospective study was approved by our institutional review board, and informed consent was waived. Seventeen patients with surgically proven early bile duct cancer who had undergone preoperative MR cholangiopancreatography with gadolinium-enhanced MR imaging, were included in this study. Two, experienced radiologists evaluated the MR images in consensus regarding the following findings: tumor number and morphology; signal intensity of the tumor; sharpness of the outer border of the bile duct wall; enhancement pattern of the tumor; and the presence of enlarged peribiliary lymph nodes. Another radiologist measured the SNR of the tumor and bile duct wall on gadolinium-enhanced MRI during the dynamic phases to evaluate the tumor enhancement degree. Results In all patients, MR imaging demonstrated single or multiple intraluminal bile duct masses showing a sharply defined outer margin. The most common enhancement pattern of the biliary lesions showed heterogeneous amorphous enhancement or heterogeneous enhancement with central, dot-like structures or vascular structures (76.5%, 13/17 patients). The difference of SNR between bile duct and tumor was greatest in the equilibrium phase ( P < 0.05). Conclusion MRCP combined with dynamic contrast-enhanced MRI can be useful for detecting early bile duct cancers. Common MR findings of early bile duct cancer include one or more inhomogeneously enhancing intraductal masses with clear outer margins and preservation of the bile duct wall. J. Magn. Reson. Imaging 2008;28:1466-1475. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To compare the diagnostic accuracy of navigator-triggered isotropic three-dimensional (3D) MR cholangiopancreatography (MRCP) using parallel imaging for malignant biliary obstruction with direct cholangiography. Materials and Methods A total of 23 patients with malignant biliary obstruction underwent MRCP and endoscopic retrograde cholangiopancreatography (ERCP)/percutaneous transhepatic cholangiography (PTC). Two observers retrospectively evaluated 3D-MRCP and ERCP/PTC and recorded the level of obstruction and extent of tumor along with their confidence. The quality of images and morphologic appearance of stricture were also evaluated by two reviewers. The results of MRCP and ERCP/PTC were compared with surgical and histopathological data. Results 3D-MRCP was of diagnostic quality and free of artifacts in all patients, whereas ERCP/PTC examinations failed in three patients. For the evaluation of level of obstruction, there was no statistical significance between 3D-MRCP and ERCP/PTC. 3D-MRCP was superior to ERCP/PTC in the assessment of anatomical extent of hilar bile duct involvement, but did not show statistical significance. The accuracy of 3D-MRCP in determining tumoral extent of hilar cancer was higher than that of ERCP/PTC, but it was not statistically significant. The image quality of 3D-MRCP was superior to ERCP/PTC. There was good agreement between morphologic appearance at MRCP and those at ERCP/PTC. Conclusion 3D-MRCP can accurately assess the level of obstruction and extent of tumor in patients with malignant biliary obstruction. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether quantitative and qualitative analysis of intraoperative Doppler sonography data are predictive of vascular complications after living-related donor liver transplantation. Methods: Intraoperative sonograms of 81 transplanted livers (right lobe in 61 patients, left lobe in 20 patients) were analyzed for the presence of blood flow, resistance index, systolic acceleration time (SAT), peak systolic velocity, and morphologic characteristics of spectral waveform of the hepatic artery. Peak velocity and spectral waveforms of portal and hepatic veins were also analyzed. Intraoperative sonography results were compared with information obtained with multidetector-row CT (MDCT) angiography or conventional angiography. The time interval between operation and angiography ranged from 1 to 23 days (mean, 8.5 days). Results: Hepatic artery stenosis (HAS) was identified in 20 patients via MDCT angiography, conventional angiography, or both. The Doppler parameters found helpful for predicting HAS were tardus-parvus pattern and delayed SAT. The sensitivity, specificity, and negative predictive value (NPV) were 60.0%, 73.7%, and 84.9%, respectively, for tardus-parvus pattern and 40.0%, 83.6%, and 80.9%, respectively, for delayed SAT. Peak velocities of the portal and hepatic veins were not reliable indicators of vascular complication. Loss of triphasity of the hepatic vein had a 98.4% NPV for venous obstruction. Conclusions: Delayed SAT of the hepatic artery and loss of triphasity of the hepatic vein had a >80% for specificity for predicting vascular complications. Tardus-parvus pattern, delayed SAT of the hepatic artery, and loss of triphasity of the hepatic vein showed an acceptable NPV for identifying vascular complications. [ABSTRACT FROM AUTHOR]

Purpose To determine imaging criteria for the combined use of contrast-enhanced (CE)-MRI and MR cholangiopancreatography (MRCP) to differentiate malignant from benign biliary strictures. Materials and Methods A total of 44 patients with biliary stricture who had undergone unenhanced, MRCP, and dynamic MRI were identified from radiological and surgical databases. Two radiologists analyzed MR features for asymmetry, luminal irregularity, abrupt narrowing, outer margin, signal intensity (SI) on T2-weighted (T2W) images, and hyperenhancement relative to liver parenchyma during portal phase. The wall thickness and length of the narrowed segment were measured. MR findings relevant as predictors were identified using a Chi-square or Fisher's exact test and the odds ratio (OR). Results The presence of hyperenhancement relative to liver parenchyma, length > 12 mm, wall thickness > 3 mm, indistinct outer margin, luminal irregularity, and asymmetry of strictured bile duct were significant factors for malignancy ( P < 0.05). Malignant strictures were significantly thicker (5.0 ± 2.0 mm) and longer (27.0 ± 13.6 mm) than benign strictures. When any three or more of these six criteria were used in combination, we could identify 100% of malignant strictures and 87.0% of benign strictures. Conclusion The combined use of CE-MRI and MRCP helped to define the criteria for differentiating malignant from benign biliary strictures in our data. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of multirow-detector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the differentiation of intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic masses. Materials and Methods: A total of 53 patients with pathologically proven pancreatic cystic lesions who had undergone MDCT and MRI were included in this study. Two radiologists analyzed the morphologic features of the lesions and graded the lesion conspicuity on each examination. The readers assigned their confidence level regarding the differentiation of IPMN from other lesions and predicting ductal communication of the lesion. The radiologists' diagnostic confidence was compared using receiver operating characteristic (ROC) analysis. Results: The Az values for each observer for predicting ductal communication of the lesion and differentiating IPMN from other lesions were as follows: For MRI they were respectively 0.949 and 0.995 for reader 1, and 0.916 and 0.932 for reader 2. For MDCT they were respectively 0.790 and 0.875 for reader 1, and 0.774 and 0.850 for reader 2. In addition, for differentiating IPMNs from other lesions, MRI was significantly more accurate than MDCT (P < 0.05) for one observer, but for the other observer there was no significant difference between the two examinations (P = 0.059). For predicting ductal communication of the cystic lesions for both observers, MRI was significantly more accurate than MDCT (P < 0.05). The weighted kappa values indicate good agreement (kappa = 0.61) between observers for MDCT, and excellent agreement (kappa = 0.82) for MRI. Conclusion: Pancreatic MRI shows better diagnostic performance than MDCT for differentiating IPMNs from other cystic lesions of the pancreas. [ABSTRACT FROM AUTHOR]

This paper derives estimating equations from a model where individuals consume two classes of goods, and the degree of contract enforcement affects the transaction cost of trade in the two classes of goods differentially. Empirically, using Rauch's classification, internationally traded goods are classified into differentiated goods and those possessing a reference price, with the presumption that contract enforcement issues are more important for the former. It is verified that the measures of contract enforcement affect the volume of trade in both types of goods, but the impact is larger for differentiated goods. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether patient age is associated with the surgical outcome after endoscopic sinus surgery (ESS) with polypectomy. Study Design: A prospective, controlled case series. Materials and Methods: This study consisted of 60 patients who were diagnosed as having chronic rhinosinusitis (CRS) with nasal polyposis (NP) that was refractory to medical treatment. Three groups were classified according to patient age: pediatric (5-18 yr), adult (19-65 yr), and geriatric (over 65 yr). We collected 20 patients in each age group after applying the exclusion criteria. The extent of the polyps and the Lund-Mackay score were calculated for each patient, and they underwent ESS with polypectomy. We compared the objective endoscopic findings and subjective improvements in symptoms among the groups 6 months after the procedure. Results: There were no statistical differences in polyp extent or Lund-Mackay score between the three age groups. The objective surgical outcome based on the endoscopic findings was worst in the pediatric group (45%), whereas the geriatric group showed the best results (90%). The differences in objective outcome among the three groups were significant, and patient age was a predictive variable for surgical result based on multiple logistic regression analysis. No major complications occurred, and the overall improvement in subjective symptoms was statistically significant in all three age groups at 6 months postoperatively. The subjective surgical outcome did not differ statistically between the groups, with the exception of olfactory disturbance. Conclusions: The results of the present study suggest that patient age influences the objective postoperative outcome in the endoscopic treatment of CRS with NP, and that ESS is an effective and reliable method for improving the subjective symptoms in patients of all age groups despite the statistically different objective surgical outcomes between the groups. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of CT angiography (CTA) and MR angiography (MRA) for preoperative hepatic vascular evaluation in living liver donors. Materials and Methods: Twenty-eight living donor candidates underwent preoperative CTA and MRA. Two blinded radiologists evaluated the anatomic types of the hepatic artery (HA) and portal vein (PV), and the number of aberrant hepatic veins (HVs) on both CTA and MRA, independently. Four grades of confidence levels were used to indicate the clarity of depiction of the HA and PV. Surgical findings were used as a standard of reference. Results: For determining the anatomic types of the HA and PV, and the number of aberrant HVs, CTA and MRA did not significantly differ in terms of accuracy ([89%, 96%, and 68% on CTA] vs. [86%, 93%, and 68% on MRA] for reader 1, P>0.05; and [93%, 100%, and 86% on CTA] vs. [89%, 93%, and 79% on MRA] for reader 2, P>0.05). Confidence for the depiction of major branches of HA and PV did not differ between CTA and MRA, except for a better depiction of the left HA (LHA) on CTA (P<0.05) Conclusion: In living donor candidates, both CTA and MRA can provide a complete evaluation of the hepatic vascular anatomy. [ABSTRACT FROM AUTHOR]