Review of Capacitive Touchscreen Technologies: Overview, Research Trends, and Machine Learning Approaches.

Touchscreens have been studied and developed for a long time to provide user-friendly and intuitive interfaces on displays. This paper describes the touchscreen technologies in four categories of resistive, capacitive, acoustic wave, and optical methods. Then, it addresses the main studies of SNR improvement and stylus support on the capacitive touchscreens that have been widely adopted in most consumer electronics such as smartphones, tablet PCs, and notebook PCs. In addition, the machine learning approaches for capacitive touchscreens are explained in four applications of user identification/authentication, gesture detection, accuracy improvement, and input discrimination.

Asymmetric Host Molecule Bearing Pyridine Core for Highly Efficient Blue Thermally Activated Delayed Fluorescence OLEDs.

In this study, two host materials, pCzBzbCz and pCzPybCz, are synthesized to achieve a high efficiency and long lifetime of blue thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs). The molecular design strategy involves the introduction of a pyridine group into the core structure of pCzPybCz as an electron-withdrawing unit, and an electron-donating phenyl group into the structure of pCzBzbCz. These host materials demonstrate good thermal stability and high triplet energy (T1 =3.07 eV for pCzBzbCz and 3.06 eV for pCzPybCz) for the fabrication of blue TADF-OLEDs. In particular, pCzPybCz-based OLED devices demonstrate an external quantum efficiency (EQE) of 22.7 % and an operational lifetime of 24 h (LT90 , time to attain 90 % of initial luminance) at an initial luminance of 1000 cd m-2 . This superior lifetime could be explained by the C-N bond dissociation energy (BDE) in the host molecular structure. Furthermore, a mixed-host system using the electron-deficient 2,4-bis(dibenzo[b,d]furan-2-yl)-6-phenyl-1,3,5-triazine (DDBFT) is proposed to inhibit the formation of the anion state of our host materials. In short, the device operational lifetime is further improved by applying DDBFT. The carbazole-based asymmetric host molecule containing a pyridine core realizes a high-efficiency blue TADF-OLED showing a positive effect on the operating lifetime, and can provide useful strategies for designing new host materials.

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects.

OBJECTIVE: The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. DESIGN: This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. PATIENTS: The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges. MEASUREMENTS: Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. RESULTS: There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. CONCLUSIONS: Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH.

Molecular Insights into the Adsorption Mechanism of Human ß-Defensin-3 on Bacterial Membranes.

Human ß-defensin-3 (hBD3) is an endogenous antimicrobial peptide that exhibits broad-spectrum antibacterial activity without eukaryotic cytotoxicity. In this work, we carried out molecular dynamics (MD) simulations to explore its adsorption mechanism on, and the structural and thermodynamic contributions of individual residues to its antibacterial activity with both Gram-negative (GN) and Gram-positive (GP) bacterial membrane. Due to the strong electrostatic interaction of hBD3 with POPG lipids, which are more prevalent on the GP membrane, its adhesion to the GP membrane is stronger than to the GN membrane and stabilized more rapidly. On the surface of both bacterial membranes, the orientation of hBD3 is dominated by an electric dipole. We next analyzed the binding free energy decompositions of the hBD3-membrane complex using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The results of both the GN and the GP membrane simulations show that Arg17, Arg36, and Arg38 form both polar and nonpolar interactions and are potentially the key residues for hBD3 antibacterial activity. On the other hand, there was a significant difference in the energy contribution of Arg12 between the GP and GN membrane simulations, suggesting that Arg12 is a key factor in the toxicity of hBD3 to specifically GP bacteria. Our findings shed light on the antibacterial activity of hBD3 on bacterial membranes and yield insights useful for the design of potent antimicrobial peptides targeting multidrug resistant bacteria.

Reduced Food-Effect on Intestinal Absorption of Dronedarone by Self-microemulsifying Drug Delivery System (SMEDDS).

The oral absorption of dronedarone (DRN), a benzofuran derivative with anti-arrhythmic activity, is significantly affected by food intake. The absolute bioavailability of the marketed product (Multaq, Sanofi, U.S.) was about 4% without food, but increased to 15% when administered with a high fat meal. Therefore, to reduce the food-effect on the intestinal absorption of DRN, a novel self-microemulsifying drug delivery system (SMEDDS) was formulated and the comparative in vivo absorption studies with the marketed product were carried out using male beagle dogs either in the fasted or fed state. The SMEDDS consisted of the drug, Labrafil M 1944CS, and Kolliphor EL in a weight ratio of 1 : 1 : 2, rapidly formed a fine oil-in-water emulsion with a droplet size less than 50 nm. An in vivo absorption study revealed that the area-under-curve (AUC0-24 h) and maximal plasma concentration (Cmax) were 10.4-fold (p<0.05) and 8.6-fold (p<0.05) higher, respectively, after the marketed product was orally administered to beagles in the fed state when compared to those in the fasted state. This food-effect were remarkably alleviated by SMEDDS formulation, with AUC0-24 h and Cmax 2.9-fold (p<0.05) and 2.6-fold (p<0.05) higher in the fed state when compared to the fasted state, by facilitating intestinal absorption of DRN in the fasted state. The results of this study suggest that SMEDDS may decrease the differences in oral absorption of DRN between the prandial states, improving therapeutic efficacy as well as patient compliance.

Preparation of solid dispersion of dronedarone hydrochloride with Soluplus(®) by hot melt extrusion technique for enhanced drug release.

In order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a novel Soluplus(®) (polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer)-based solid dispersion (SD) was formulated using a hot melt extrusion technique. The physical characteristics determined using scanning electron microscopy and X-ray powder diffraction, revealed that the active compound was molecularly dispersed in the amphiphilic polymer in a stable amorphous form. The dissolution rate of DRN from the tablet dosage form of SD extrudate consisted of the drug and Soluplus(®) in a weight ratio of 1 : 1, and was obviously more rapid and higher than that of the intact drug and marketed product (Multaq(®), Sanofi, U.S.A.) at pH 1.2, 4.0 and 6.8. This suggests that Soluplus(®)-based SD formula can be a promising approach for enhancing the dissolution and oral absorption of DRN with a simple preparation process.

Designing Chemically Replaced Interfacial Layer via Unveiling the Influence of Zn Crystal Facets for Practical Zn-Metal Anodes.

Zn metal anodes (ZMAs) undergo irregular deposition and unfavorable side reactions, which hinders the practical application of aqueous rechargeable Zn metal batteries (ARZMBs). Chemical replacement reaction (CRR) strategies can achieve stable ZMAs, but the effect of the crystal facets of metallic Zn as reductants remains poorly understood. In this study, based on the observation that preferentially exposed Zn crystal facets affect the surface characteristics of chemically replaced layers in Sn-based CRR, a multifunctional Sn-based interfacial layer (ZnTCF@Sn) is designed on the Zn with textured crystal facets using a novel two-step CRR process. ZnTCF@Sn simultaneously provides abundant zincophilic sites and high surface energy and homogenizes the distribution of current/Zn2+ flux, resulting in fast electrochemical kinetics and dendrite-free deposition. Furthermore, the uniform Sn coverage on the ZnTCF@Sn surface inhibits side reactions and enhances reversibility during Zn deposition/dissolution. Thus, the ZnTCF@Sn achieves exceptional cyclability over 1200 h even under harsh operating conditions with a cumulative capacity of 24 Ah cm-2 . This study contributes to the development of practical ARZMBs by providing new insights into the effect of the Zn crystal facets on the surface modification of ZMAs through various CRRs.

Enhancement of polyhydroxybutyrate production by introduction of heterologous phasin combination in Escherichia coli.

Phasin is a surface-binding protein of polyhydroxyalkanoate (PHA) granules that is encoded by the phaP gene. As its expression increases, PHA granules become smaller, to increase their surface area, and are densely packed inside the cell, thereby increasing the PHA content. A wide range of PHA-producing bacteria have phaP genes; however, their PHA productivity differs, although they are derived from the cognate bacterial host cell. Modulating phasin expression could be a new strategy to enhance PHA production. This study aimed to characterize the effect of heterologous phasins on the reconstitution of E. coli BL21(DE3) and determine the best synergistic phaP gene combination to produce polyhydroxybutyrate (PHB). We identified novel phasins from a PHB high-producer strain, Halomonas sp. YLGW01, and introduced a combination of phaP genes into Escherichia coli. The resulting E. coli phaP1,3 strain had enhanced PHB production by 2.9-fold, leading to increased cell mass and increased PHB content from 48 % to 65 %. This strain also showed increased tolerance to inhibitors, such as furfural and vanillin, enabling the utilization of lignocellulose biosugar as a carbon source. These results suggested that the combination of phaP1 and phaP3 genes from H. sp. YLGW01 could increase PHB production and robustness.

Real-time concealed-object detection and recognition with passive millimeter wave imaging.

Millimeter wave (MMW) imaging is finding rapid adoption in security applications such as concealed object detection under clothing. A passive MMW imaging system can operate as a stand-off type sensor that scans people in both indoors and outdoors. However, the imaging system often suffers from the diffraction limit and the low signal level. Therefore, suitable intelligent image processing algorithms would be required for automatic detection and recognition of the concealed objects. This paper proposes real-time outdoor concealed-object detection and recognition with a radiometric imaging system. The concealed object region is extracted by the multi-level segmentation. A novel approach is proposed to measure similarity between two binary images. Principal component analysis (PCA) regularizes the shape in terms of translation and rotation. A geometric-based feature vector is composed of shape descriptors, which can achieve scale and orientation-invariant and distortion-tolerant property. Class is decided by minimum Euclidean distance between normalized feature vectors. Experiments confirm that the proposed methods provide fast and reliable recognition of the concealed object carried by a moving human subject.

Real-time outdoor concealed-object detection with passive millimeter wave imaging.

Millimeter wave imaging is finding rapid adoption in security applications such as the detection of objects concealed under clothing. A passive imaging system can be realized as a stand-off type sensor that can operate in open spaces, both indoors and outdoors. In this paper, we address real-time outdoor concealed-object detection and segmentation with a radiometric imaging system operating in the W-band. The imaging system is equipped with a dielectric lens and a receiver array operating at around 94 GHz. Images are analyzed by multilevel segmentation to identify a concealed object. Each level of segmentation comprises vector quantization, expectation-maximization, and Bayesian decision making to cluster pixels on the basis of a Gaussian mixture model. In addition, we describe a faster process that adopts only vector quantization for the first level segmentation. Experiments confirm that the proposed methods provide fast and reliable detection and segmentation for a moving human subject carrying a concealed gun.

Protective effects of decursin and decursinol angelate against amyloid ß-protein-induced oxidative stress in the PC12 cell line: the role of Nrf2 and antioxidant enzymes.

The protective effects of decursin (D) and decursinol angelate (DA) purified from Angelica gigas Nakai on amyloid ß-protein (Aß)-induced neurotoxicity and the underlying mechanisms were investigated. Aß plays a major role in the pathogenesis of Alzheimer's disease (AD) by eliciting oxidative stress. It significantly increased cytotoxicity and lipid peroxidation, but decreased glutathione contents and antioxidant enzyme activities. All of these results were markedly reversed by pretreatment with D or DA. Nuclear transcription factor Nrf2, which regulates the expression of antioxidant enzymes, was significantly increased by D or DA pretreatment. Furthermore, D and DA suppressed Aß aggregation. These results suggest that D and DA increase cellular resistance to Aß-induced oxidative injury in the rat pheochromocytoma (PC12) cells, presumably through not only the induction of Nrf2 and related antioxidant enzymes, but also the anti-aggregation of Aß. Thus D and DA have therapeutic potential in treating AD and other oxidative stress-related diseases.

Sonographic findings in Nicolau syndrome following intramuscular diclofenac injection: a case report.

Nicolau syndrome (also known as embolia cutis medicamentosa and livedoid dermatitis) is a rare but severe localized adverse drug reaction of intramuscular injection of various drugs. The typical presentation is pain around the injection site soon after injection, followed by erythema, livedoid patch, hemorrhagic patch, and finally necrosis of skin, subcutaneous fat, and muscle tissue. We report a case that occurred in a 34-year-old woman after intramuscular injection of diclofenac sodium. Sonography showed diffuse thickening with increased echogenicity of the skin and subcutaneous fat layer, while MRI revealed extensive edema involving gluteal and piriformis muscles and deep fascia, and fluid collection.

Heat shock augments angiotensin II-induced vascular contraction through increased production of reactive oxygen species.

A temporal increase in temperature triggers a series of stress responses and alters vascular smooth muscle (VSM) contraction induced by agonist stimulation. Here we examined the role of reactive oxygen species (ROS) in heat shock-dependent augmentation of angiotensin II (AngII)-induced VSM contraction. Endothelium-denuded rat aortic rings were treated with heat shock for 45 min at 42 degrees C and then subjected to assays for the production of force, ROS, and the expression of ROS-related enzymes. AngII-induced contraction was enhanced in heat shock-treated aorta. AngII-induced production of hydrogen peroxide and superoxide were elevated in response to the heat shock treatment. Pre-treatment with superoxide dismutases (SOD) mimetic and inhibitors for glutathione peroxidase and NADPH oxidase but not for xanthine oxidase eliminated an increase in the AngII-induced contraction in the heat shock-treated aorta. Heat shock increased the expression of p47phox, a cytosolic subunit of NADPH oxidase, but not Cu-Zn-SOD and Mn-SOD. In addition, heat shock increased contraction that was evoked by hydrogen peroxide and pyrogallol. These results suggest that heat shock causes an elevation of ROS as well as a sensitization of ROS signal resulting in an augmentation of VSM contraction in response to agonist.

Synthesis of Tungsten-Doped Vanadium Dioxide Using a Modified Polyol Method Involving 1-Dodecanol.

The doping of tungsten into VO2 (M) via a polyol process that is based on oligomerization of ammonium metavanadate and ethylene glycol (EG) to synthesize a vanadyl ethylene glycolate (VEG) followed by postcalcination was carried out by simply adding 1-dodecanol and the tungsten source tungstenoxytetrachloride (WOCl4). Tungsten-doped VEGs (W-VEGs) and their calcinated compounds (WxVO2) were prepared with varying mixing ratios of EG to 1-dodecanol and WOCl4 concentrations. Characterizations of W-VEGs by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and infrared and transmittance spectroscopy showed that tungsten elements were successfully doped into WxVO2, thereby decreasing the metal-insulator transition temperature from 68 down to 51 °C. Our results suggested that WOCl4 variously combined with 1-dodecanol might interrupt the linear growth of W-VEGs, but that such an interruption might be alleviated at the optimal 1:1 mixing ratio of EG to 1-dodecanol, resulting in the successful W doping. The difference in the solar modulations of a W0.0207VO2 dispersion measured at 20 and 70 °C was increased to 21.8% while that of a pure VO2 dispersion was 2.5%. It was suggested that WOCl4 coupled with both EG and 1-dodecanol at an optimal mixing ratio could improve the formation of W-VEG and WxVO2 and that the bulky dodecyl chains might act as defects to decrease crystallinity.

Cancer genetic markers according to radiotherapeutic response in patients with primary glioblastoma - Radiogenomic approach for precision medicine.

BACKGROUND AND PURPOSE: To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GB) patients. MATERIALS AND METHODS: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GB were treated with surgery and adjuvant concurrent chemoradiotherapy with the Stupp's regimen, and then genomic research proceeded with their surgical specimens. Among the 161 patients, 49 with clinically measurable disease on postoperative MRI were analyzed. The response evaluation to RT was based on Response Assessment in Neuro-Oncology (RANO) criteria. For genomic analyses to compare between patients with progression and non-progression, Fisher test for DNA mutations and copy number alterations and the Gene Set Enrichment Analysis (GSEA) were performed. RESULTS: RT responses were non-progressive and progressive disease (PD) in 22 (44.9%) and 27 patients (55.1%), respectively. After three months, seven of PD exhibited pseudoprogression. For true response adjusting pseudoprogression from PD, 1-year progression-free survival for true Non-Responders (tNR-group) and true Responders (tR-group) were 0% and 45.4% (p < 0.001), and overall survival were 52.5% and 81.1% (p = 0.046), respectively. In genomic analyses, the tNR-group had more CDKN2A deletions (94.4% vs. 55.6%, p = 0.013), EGFR mutations (33.3% vs. 3.7%, p = 0.012) and less TP53 mutations (22.2% vs. 40.7%, p = 0.333) than the tR-group. In GSEA, immune-related gene sets were enriched in the tNR-group, and in contrast, some gene sets related with cell cycle were enriched in tR-groups. CONCLUSION: The RANO criteria were feasible for the short-term response evaluation from RT despite of pseudoprogression. Genomic differences such as CDKN2A deletion, EGFR mutation, and immune- or inflammation-related related gene sets enrichment were found to be potentially predictive markers of RT.

Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma.

Background: Despite extensive efforts on the genomic characterization of gliomas, very few studies have reported the genetic alterations of cerebellar glioblastoma (C-GBM), a rare and lethal disease. Here, we provide a systematic study of C-GBM to better understand its specific genomic features. Methods: We collected a cohort of C-GBM patients and compared patient demographics and tumor pathologies with supratentorial glioblastoma (S-GBM). To uncover the molecular characteristics, we performed DNA and mRNA sequencing and DNA methylation arrays on 19, 6, and 4 C-GBM cases, respectively. Moreover, chemical drug screening was conducted to identify potential therapeutic options for C-GBMs. Results: Despite differing anatomical origins of C-GBM and S-GBM, neither histological, cytological, nor patient demographics appeared significantly different between the 2 types. However, we observed striking differences in mutational patterns, including frequent alterations of ATRX, PDGFRA, NF1, and RAS and absence of EGFR alterations in C-GBM. These results show a distinct evolutionary path in C-GBM, suggesting specific therapeutic targeted options. Targeted-drug screening revealed that C-GBMs were more responsive to mitogen-activated protein kinase kinase (MEK) inhibitor and resistant to epidermal growth factor receptor inhibitors than S-GBMs. Also, differential expression analysis indicated that C-GBMs may have originated from oligodendrocyte progenitor cells, suggesting that different types of cells can undergo malignant transformation according to their location in brain. Master regulator analysis with differentially expressed genes between C-GBM and proneural S-GBM revealed NR4A1 as a potential therapeutic target. Conclusions: Our results imply that unique gliomagenesis mechanisms occur in adult cerebellum and new treatment strategies are needed to provide greater therapeutic benefits for C-GBM patients. Key Points: 1. Distinct genomic profiles of 19 adult cerebellar GBMs were characterized. 2. MEK inhibitor was highly sensitive to cerebellar GBM compared with supratentorial GBM. 3. Master regulator analysis revealed NR4A1 as a potential therapeutic target in cerebellar GBM.

Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations.

Cannabinoid receptor 1 (CB1) is a promising therapeutic target for a variety of disorders. Distinct efficacy profiles showed different therapeutic effects on CB1 dependent on three classes of ligands: agonists, antagonists, and inverse agonists. To discriminate the distinct efficacy profiles of the ligands, we carried out molecular dynamics (MD) simulations to identify the dynamic behaviors of inactive and active conformations of CB1 structures with the ligands. In addition, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method was applied to analyze the binding free energy decompositions of the CB1-ligand complexes. With these two methods, we found the possibility that the three classes of ligands can be discriminated. Our findings shed light on the understanding of different efficacy profiles of ligands by analyzing the structural behaviors of intact CB1 structures and the binding energies of ligands, thereby yielding insights that are useful for the design of new potent CB1 drugs.

Water Pharmacophore: Designing Ligands using Molecular Dynamics Simulations with Water.

In this study, we demonstrate a method to construct a water-based pharmacophore model which can be utilized in the absence of known ligands. This method utilizes waters found in the binding pocket, sampled through molecular dynamics. Screening of compound databases against this water-based pharmacophore model reveals that this approach can successfully identify known binders to a target protein. The method was tested by enrichment studies of 7 therapeutically important targets and compared favourably to screening-by-docking with Glide. Our results suggest that even without experimentally known binders, pharmacophore models can be generated using molecular dynamics with waters and used for virtual screening.

Nitrogen Doping of Carbon Nanoelectrodes for Enhanced Control of DNA Translocation Dynamics.

Controlling the dynamics of DNA translocation is a central issue in the emerging nanopore-based DNA sequencing. To address the potential of heteroatom doping of carbon nanostructures and for achieving this goal, herein, we carry out atomistic molecular dynamics simulations for single-stranded DNAs translocating between two pristine or doped carbon nanotube (CNT) electrodes. Specifically, we consider the substitutional nitrogen doping of capped CNT (capCNT) electrodes and perform two types of molecular dynamics simulations for the entrapped and translocating single-stranded DNAs. We find that the substitutional nitrogen doping of capCNTs facilitates and stabilizes the edge-on nucleobase configurations rather than the original face-on ones and slows down the DNA translocation speed by establishing hydrogen bonds between the N dopant atoms and nucleobases. Due to the enhanced interactions between DNAs and N-doped capCNTs, the duration time of nucleobases within the nanogap was extended by up to ∼300%. Given the possibility to be combined with the extrinsic light or gate voltage modulation methods, the current work demonstrates that the substitutional nitrogen doping is a promising direction for the control of DNA translocation dynamics through a nanopore or nanogap, based of carbon nanomaterials.

Elucidating the Bacterial Membrane Disruption Mechanism of Human α-Defensin 5: A Theoretical Study.

Human α-defensin 5 (HD5) is a broad-spectrum antibacterial peptide produced by small intestinal Paneth cells. Despite considerable experimental evidence for the correlation between bacterial membrane destruction and the antibacterial activity of HD5, its membrane disruption mechanism remains unclear. Using all-atom molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area analysis, we demonstrate the membrane disruption mechanism of HD5 based on the intrinsic binding of HD5 to Gram-negative (GN) bacterial inner membrane. It was found that both monomer and dimer forms of HD5 bind to the surface of the GN membrane rather than embedding in the hydrophobic core region of the bilayer. Regardless of the form of HD5, the peptide orientated itself similarly on the membrane surface with an inward-pointing electric dipole moment and an outward-pointing hydrophobic dipole moment. We investigated its possible membrane disruption mechanisms and determined that anionic lipid clustering is a plausible mode of action for HD5. Relative binding free energy analysis revealed that electrostatic interactions play a major role in this mechanism. Our findings shed light on the biophysical phenomena of HD5-GN membrane binding and suggest a possible membrane disruption mechanism for HD5. This analysis of the fundamental binding properties of the monomeric HD5-GN membrane complex provides a useful guide for defensin-derived antibiotic design.