Search

Abstract The fabrication and development of high-entropy alloys (HEAs) with exceptional functionalities is a rapidly expanding field with numerous applications. When the role of entropy in HEAs is considered, the extrinsic factors, such as the existence of grains and different phases, need to be separated from the intrinsic configurations of the atomic lattice. Here, we fabricated the CoCrFeNi2Al0.5 HEA/muscovite heterostructures, and some were prepared as epitaxial bilayers and others were prepared as an amorphous system. These two systems are classified into atomic-site disordered (ASD) and structurally disordered (SD) states, respectively, without the extrinsic effects for the determination of the crystal lattice role in high-entropy states. In this study, we determined the role of the structure order in correlation with the structural, electronic, and magnetic properties of HEAs using a combination of energy-dispersive X-ray spectrometry, X-ray diffraction, transmission electron microscopy, magneto-transport, ac magnetometry, and X-ray absorption spectroscopy with magnetic circular dichroism. The ASD state showed fully metallic behavior. In contrast, the SD state showed a metallic behavior with intense magnetic saturation, which was called Kondo-like behavior, under 50 K with a low-temperature coefficient of resistivity of ~64 ppm/°C. The difference between the saturation magnetic moment and the electron relaxation behavior in the ASD and SD states resulted from the existence of the structural order affecting the atomic distance and periodicity to modify the exchange interaction and tune the electron-phonon interaction for scattering. The ferromagnetic behavior contributed by Co, Fe, and Ni atoms was probed by X-ray absorption and magnetic circular dichroism to understand the magnetic interactions in the ASD and SD states.

Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan–Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.

In ethnographic research, data collected through surveys, interviews, or questionnaires in the fields of sociology and anthropology often appear in diverse forms and languages. Building a powerful database system to store and process such data, as well as making good and efficient queries, is very challenging. This paper extensively investigates modern database technology to find out what the best technologies to store these varied and heterogeneous datasets are. The study examines several database categories: traditional relational databases, the NoSQL family of key-value databases, graph databases, document databases, object-oriented databases and vector databases, crucial for the latest artificial intelligence solutions. The research proves that when it comes to field data, the NoSQL lineup is the most appropriate, especially document and graph databases. Simplicity and flexibility found in document databases and advanced ability to deal with complex queries and rich data relationships attainable with graph databases make these two types of NoSQL databases the ideal choice if a large amount of data has to be processed. Advancements in vector databases that embed custom metadata offer new possibilities for detailed analysis and retrieval. However, converting contents into vector data remains challenging, especially in regions with unique oral traditions and languages. Constructing such databases is labor-intensive and requires domain experts to define metadata and relationships, posing a significant burden for research teams with extensive data collections. To this end, this paper proposes using Generative AI (GenAI) to help in the data-transformation process, a recommendation that is supported by testing where GenAI has proven itself a strong supplement to document and graph databases. It also discusses two methods of vector database support that are currently viable, although each has drawbacks and benefits.

Abstract Background Dysregulated long noncoding RNA (lncRNA) expression with increased apoptosis has been demonstrated in systemic lupus erythematosus (SLE) patients with alveolar hemorrhage (AH). SNHG16, a lncRNA, can enhance pulmonary inflammation by sponging microRNAs, and upregulate toll-like receptor 4 (TLR4) expression via stabilizing its mRNAs. TRAF6, a TLR4 downstream signal transducer, can induce autophagy and NETosis formation. In this study, we investigated whether SNHG16 could regulate TLR4-mediated autophagy and NETosis formation in SLE-associated AH. Methods Expression of SNHG16, TLR4 and TRAF6 and cell death processes were examined in lung tissues and peripheral blood (PB) leukocytes from AH patients associated with SLE and other autoimmune diseases, and in the lungs and spleen from a pristane-induced C57BL/6 mouse AH model. SNHG16-overexpressed or -silenced alveolar and myelocytic cells were stimulated with lipopolysaccharide (LPS), a TLR4 agonist, for analyzing autophagy and NETosis, respectively. Pristane-injected mice received the intra-pulmonary delivery of lentivirus (LV)-SNHG16 for overexpression and prophylactic/therapeutic infusion of short hairpin RNA (shRNA) targeting SNHG16 to evaluate the effects on AH. Renal SNHG16 expression was also examined in lupus nephritis (LN) patients and a pristane-induced BALB/c mouse LN model. Results Up-regulated SNHG16, TLR4 and TRAF6 expression with increased autophagy and NETosis was demonstrated in the SLE-AH lungs. In such patients, up-regulated SNHG16, TLR4 and TRAF6 expression was found in PB mononuclear cells with increased autophagy and in PB neutrophils with increased NETosis. There were up-regulated TLR4 expression and increased LPS-induced autophagy and NETosis in SNHG16-overexpressed cells, while down-regulated TLR4 expression and decreased LPS-induced autophagy and NETosis in SNHG16-silenced cells. Pristane-injected lung tissues had up-regulated SNHG16, TLR4/TRAF6 levels and increased in situ autophagy and NETosis formation. Intra-pulmonary LV-SNHG16 delivery enhanced AH through up-regulating TLR4/TRAF6 expression with increased cell death processes, while intra-pulmonary prophylactic and early therapeutic sh-SNHG16 delivery suppressed AH by down-regulating TLR4/TRAF6 expression with reduced such processes. In addition, there was decreased renal SNHG16 expression in LN patients and mice. Conclusions Our results demonstrate that lncRNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in the human and mouse AH lungs, and provide a therapeutic potential of intra-pulmonary delivery of shRNA targeting SNHG16 in this SLE-related lethal manifestation.

Summary: Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants. ProT transgenic mice had reduced platelet counts with prolonged bleeding times. Upon treatment with DENV plus anti-CD41 antibody, they exhibited severe skin hemorrhage. Furthermore, overexpression of ProT suppressed megakaryocyte differentiation. Infection with DENV inhibited miR-126 expression, upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1), downregulated GATA-1, and increased ProT expression. Upregulation of ProT led to Nrf2 activation and reduced reactive oxygen species production, thereby suppressing megakaryopoiesis. We report the pathophysiological role of ProT in DENV infection and propose an involvement of the miR-126-DNMT1-GATA-1-ProT-Nrf2 signaling axis in DENV-induced thrombocytopenia.

The advancement of flexible technology, such as wearable devices, foldable mobile, and automobiles, has entered a new era. Recently, MICAtronics using flexible muscovite carriers has been introduced as a novel area for flexible technology. The muscovite substrate addresses challenges such as thermal budget and chemical stability, offering outstanding environmental stability and an alternative approach to the prevalent polymer-based soft technology. However, the role of muscovite in these studies has been limited to serving as substrates. We expand the scope of muscovite applications by proposing a new form called “intercalated muscovite.” In this study, we insert transition metal ions, creating a novel layout of muscovite substrates. Subsequent heat treatment and controlled atmospheres can generate various forms of inserted species. These intercalated systems reveal new physical properties of muscovite substrates, offering a fresh avenue for MICAtronics.

Abstract Background and aim World Health Organization sets up an ambitious and attainable goal to eliminate hepatitis C (HCV) by 2030. The previous diagnosed HCV patients lost to follow-up were considered as an important target group for HCV elimination. We conducted a call back program to retrieve the lost to follow-up HCV patients and link them to care in our hospital. By analyzing and comparing our result with that from other studies, we wish to improve our retrieval strategy and provide our experience to the general communities. Methods A list of the patients with a medical record showing seropositive for antibody to HCV (anti-HCV Ab) from 2004 to 2017 was retrieved by the department of intelligent technology of our hospital. Three dedicated staff members reviewed the patients’ electronic medical records (EMRs) and recruited the patient lost follow-up to the call back program. The staff members contacted the qualified patients by telephone and inquired about their opinions for treating their chronic HCV infection. We also informed the patients about the retrieval strategy and why we contact them. As our National Health Insurance request, we gave all patient one informed consent for hepatitis C treatment. Informed consents have been obtained from all patients. Referrals to our gastroenterology unit (GU) were arranged for the patients who would like to continue their chronic HCV care in our hospital. Results There were 31,275 anti-HCV positive patients. We included 11,934 patients (38.2%) into the call back system and contacted them by telephone. Based on the response to our call, we ascertained 1277 eligible cases (10.7%) for retrieval. The patients who were younger (

Abstract Background Influenza is one of the most important viral infections globally. Viral RNA-dependent RNA polymerase (RdRp) consists of the PA, PB1, and PB2 subunits, and the amino acid residues of each subunit are highly conserved among influenza A virus (IAV) strains. Due to the high mutation rate and emergence of drug resistance, new antiviral strategies are needed. Host cell factors are involved in the transcription and replication of influenza virus. Here, we investigated the role of galectin-3, a member of the β-galactoside-binding animal lectin family, in the life cycle of IAV infection in vitro and in mice. Methods We used galectin-3 knockout and wild-type mice and cells to study the intracellular role of galectin-3 in influenza pathogenesis. Body weight and survival time of IAV-infected mice were analyzed, and viral production in mouse macrophages and lung fibroblasts was examined. Overexpression and knockdown of galectin-3 in A549 human lung epithelial cells were exploited to assess viral entry, viral ribonucleoprotein (vRNP) import/export, transcription, replication, virion production, as well as interactions between galectin-3 and viral proteins by immunoblotting, immunofluorescence, co-immunoprecipitation, RT-qPCR, minireplicon, and plaque assays. We also employed recombinant galectin-3 proteins to identify specific step(s) of the viral life cycle that was affected by exogenously added galectin-3 in A549 cells. Results Galectin-3 levels were increased in the bronchoalveolar lavage fluid and lungs of IAV-infected mice. There was a positive correlation between galectin-3 levels and viral loads. Notably, galectin-3 knockout mice were resistant to IAV infection. Knockdown of galectin-3 significantly reduced the production of viral proteins and virions in A549 cells. While intracellular galectin-3 did not affect viral entry, it increased vRNP nuclear import, RdRp activity, and viral transcription and replication, which were associated with the interaction of galectin-3 with viral PA subunit. Galectin-3 enhanced the interaction between viral PA and PB1 proteins. Moreover, exogenously added recombinant galectin-3 proteins also enhanced viral adsorption and promoted IAV infection in A549 cells. Conclusion We demonstrate that galectin-3 enhances viral infection through increases in vRNP nuclear import and RdRp activity, thereby facilitating viral transcription and replication. Our findings also identify galectin-3 as a potential therapeutic target for influenza.

In this paper, a high-precision rotary encoder based on a sinusoidal transmissive pattern (STP) is proposed for detecting shaft rotation. The STP disk can be realized by coating bell-shaped transmissive area on a transparent glass. We optimize the STP design shape and parameters to achieve sinusoidal transmissive characteristics. The STP-based encoder consists of a light-emitting diode, a STP disk, and a photodetector array. Experimentally, the produced STP disk had a diameter of 60 mm. 256 columns of STPs were arranged on the circumference of this disk to provide a detection pitch of 1.40625°. Each column consisted of 50 bell-shaped STPs. In principle, an incident beam from a blue-ray light emitting diode illuminates the STP of the disk, and the angle of rotation is decoded from the sinusoidal distribution of transmissive spots on the PD. Compared with a conventional incremental rotary encoder, the proposed STP-based encoder achieves a superior angular resolution.

Abstract. Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited. We aimed to explore the efficacy after 1-year TAF treatment. A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it is strongly associated with obesity. To combat obesity, artificial sweeteners are often used to replace natural sugars, and sucralose is one of the most extensively used sweeteners. It was known that sucralose exerted effects on lipid metabolism dysregulation, and hepatic inflammation; however, the effects of sucralose on hepatic steatosis were still obscure. In this study, we found that supplements of sucralose enhanced high-fat-diet (HFD)-induced hepatic steatosis. In addition, treatment of sucralose increased reactive oxygen species (ROS) generation and induced endoplasmic reticulum (ER) stress in HepG2 cells. Pretreatment of ROS or ER stress inhibitors reversed the effects of sucralose on lipogenesis. Furthermore, pretreatment of taste receptor type 1 membrane 3 (T1R3) inhibitor or T1R3 knockdown reversed sucralose-induced lipogenesis in HepG2 cells. Taken together, sucralose might activate T1R3 to generate ROS and promote ER stress and lipogenesis, and further accelerate to the development of hepatic steatosis.

Abstract Background The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS. Methods We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed. Results A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (all p > 0.05). Conclusions HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.

Background & aims: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) patients. Variceal bleeding is a life-threatening complication and may alter the initial treatment plan. This study was aimed to elucidate the risk factors for variceal bleeding in HCC patients receiving TACE treatment. Methods: From 2005 to 2016, a total of 1233 treatment-naive HCC patients receiving first time TACE treatment in Chang Gung Memorial Hospital, Linkou medical center were recruited. Pre-TACE status including baseline characteristics, prior history of ascites, and parameters for liver function evaluation were analyzed. All the variables were compared between patients with and without variceal bleeding. Results: Among the 1233 patients, the median age was 63.7 (range 25.8–91.5) years old, and 73.5% were male. Variceal bleeding events were documented in 19 patients (1.5%) within 3 months post TACE treatment. Patients with younger age, cirrhosis, pre-treatment ascites and advanced fibrosis status (higher MELD score, CTP score, ALBI grade, FIB-4 and APRI score) were more likely to encounter post-treatment variceal bleeding. Multivariate Cox regression analysis revealed existence of ascites (adjusted HR: 4.859 (1.947–12.124), p = 0.001), and higher FIB-4 score (adjusted HR: 4.481 (1.796–11.179), p = 0.001) were the independent predictive factors for variceal bleeding. Patients with post-TACE variceal bleeding are more likely to encounter tumor progression (42.1% vs. 20.3%, p = 0.039) and mortality owing to GI bleeding (15.8% vs. 3%, p = 0.032). Conclusion: The incidence of post-TACE variceal bleeding was 1.5%. Patients with post-TACE variceal bleeding have poorer TACE treatment response. The pre-treatment ascites and FIB-4 score are the independent predictors for post-TACE variceal bleeding. Keywords: Ascites, Gastrointestinal bleeding, Mortality, Portal hypertension, Treatment response

Gramicidin A (gA) is a linear antimicrobial peptide that can form a channel and specifically conduct monovalent cations such as H+ across the lipid membrane. The antimicrobial activity of gA is associated with the formation of hydroxyl free radicals and the imbalance of NADH metabolism, possibly a consequence caused by the conductance of cations. The ion conductivity of gramicidin A can be blocked by Ca2+ ions. However, the effect of Ca2+ ions on the antimicrobial activity of gA is unclear. To unveil the role of Ca2+ ions, we examined the effect of Ca2+ ions on the antimicrobial activity of gramicidin A against Staphylococcus aureus (S. aureus). Results showed that the antimicrobial mechanism of gA and antimicrobial activity by Ca2+ ions are concentration-dependent. At the low gA concentration (≤1 μM), the antimicrobial mechanism of gA is mainly associated with the hydroxyl free radical formation and NADH metabolic imbalance. Under this mode, Ca2+ ions can significantly inhibit the hydroxyl free radical formation and NADH metabolic imbalance. On the other hand, at high gA concentration (≥5 μM), gramicidin A acts more likely as a detergent. Gramicidin A not only causes an increase in hydroxyl free radical levels and NAD+/NADH ratios but also induces the destruction of the lipid membrane composition. At this condition, Ca2+ ions can no longer reduce the gA antimicrobial activity but rather enhance the bacterial killing ability of gramicidin A.

Background: Secondary prevention of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC) who achieve sustained virologic response (SVR) with interferon-based therapy has been proved effective. However, tertiary prevention with PegIFN/RBV therapy of HCC recurrence seems limited effect in CHC-HCC patients post curative therapies. This study aims to investigate the timing and impact of PegIFN/RBV treatment on prevention of HCC recurrence in patients after RFA treatment. Methods: From 2013 to 2016, a total of 137 CHC-HCC patients from a 508 patient based cohort receiving complete RFA treatment in Chang Gung Memorial Hospital, Linkou Medical Center were retrospectively recruited. Pre-RFA patient demographics were analyzed by cox regression analysis for prediction on tumor recurrence. Statistics analysis was performed with SPSS V.20 (IBM, USA). Results: The mean age of the 137 patients were 69.6 year-old and 71.5% of patients were cirrhotic. After propensity score matching, one hundred and two patients were enrolled into the analysis. Fifty-one patients (50%) received PegIFN/RBV therapy and twenty-seven patients (52.9%) achieved SVR. Patients who could achieve SVR had lower tumor recurrence rate than non-SVR and untreated groups (29.6% vs. 66.7% vs. 49.0%, P = 0.030). The effect is more prominent in those achieve SVR prior to compared with after RFA despite not reach statistically significant (26.1% vs. 50.0%, P = 0.334). Conclusion: Timely treatment with SVR achievement has the lowest tumor recurrence rate in CHC-HCC patients. Secondary prevention might be even more important than tertiary prevention in CHC patients, especially regarding prevention of post RFA HCC recurrence. Keywords: Radiofrequency ablation, Haptocellular carcinoma, Peginterferon and ribavirin, Prognosis

Technology has reshaped the workplace and the rapid improvements have transformed how we work nowadays. In the pursuit of industry 4.0, we build smart machines and robots to replace manual labor. While the manual labor is replaced by machines, in many cases, humans are trans-formed into desktop software users. Jobs such as testing, quality inspection, data monitoring, data entry, and routine editing remain to be done by humans in front of desktop computers. The operations to software applications in principle can be reduced to screen output understanding and mouse and keyboard operations. When the characteristics of these jobs are repetitive, tedious, and monotonous, they can be replaced by GUI automation techniques. GUI automation can be achieved by different un-derlying technologies, each has its pros and cons. In this paper, we describe a tool-Korat, which uses computer-vision to achieve maximum cross-platform capability for industrial applications, including test automation and robotic process automation. Although Korat has been successfully adopted by several industrial customers, difficult problems remain to be addressed. The problems and difficulties in applying computer vision for GUI automation are discussed and studied in this paper, particularly the experiences of applying open source OCR to GUI automation over color screenshots. By intro-ducing critical pre-processing stages and algorithms, the recognition rate is significantly increased and becomes feasible for practical usage.

This study proposed a novel methodology for reducing the vibration of a high-speed spur gear pair (up to 30,000 rpm) by performing multi-objective optimization of the peak-to-peak loaded transmission error (PPLTE) under three assembly conditions. The optimum tip relief parameters for the high-speed spur gear set were studied by considering the practical manufacturing tolerances on the gear shaft and bearing bores. First, the PPLTE under three assembly conditions was determined by loaded tooth contact analysis. Multi-objective optimization with a genetic algorithm was used to determine the optimum linear tip relief parameters, minimizing the PPLTE under three assembly conditions by 70%. Moreover, the dynamic characteristics of the original and optimum designs were simulated and compared under ideal conditions as well as axial misalignments. The optimum design exhibited a >50% reduction in the peak RMS of acceleration at the natural frequency. Finally, dynamic experiments were performed and the RMS values of the acceleration at various speeds were computed for comparison. The results from both dynamic simulation and experiment indicated that the optimum design exhibits superior dynamic characteristics to the original design.

This study proposed an energy harvester that combines an eccentric pendulum with Wiegand wires to harvest the kinetic energy of a rotating plate. The energy harvester converts the kinetic energy into electrical energy to power sensors mounted on the rotating plate or wheel. The kinetic model is derived from the Euler–Lagrange equation. The eccentric pendulum generates a swing motion from the direction variation of the centrifugal force and the gravitational force. The magnetic circuit is designed such that, during the swing motion, an alternating magnetic field is formed to induce the output voltage of the Wiegand wire. COMSOL software was used to simulate magnetic flux density and optimize the geometric parameters of magnets. Response surface methodology was used to formulate the output voltage model. Magnetic flux density affects output voltage dramatically. However, the output voltage is not sensitive to the gradient of magnetic flux density. The experimental results indicate that when the Wiegand wire is 14.2 mm from the magnet, the generation power is 0.118–1.15 mW, in a speed range of 240–540 rpm. When the Wiegand wire is 7.0 mm from the magnet, the generation power is 0.741–1.06 mW, in a speed range of 480–660 rpm.

In this study, static and dynamic analyses of a spur gear pair with linear tip relief and longitudinal crowning were performed. Dynamic experiments were conducted to compare and verify the dynamic analysis results. On the basis of the theory of gearing, the mathematical model of a modified spur gear pair was established. In addition, a finite element mesh generation program was developed according to the mathematical model. Finite element analysis was applied to calculate the contact stress, contact patterns, and mesh stiffness of the gear pair. Moreover, a dynamic analysis was performed to predict the dynamic transmission error (DTE) at various speeds and loads. Dynamic experiments were performed on the spur gear pair by using a gear dynamic tester. Accelerometers were mounted on the gear pair to record the vibrations during gear meshing. The experimental DTE was calculated and compared with the simulated DTE to verify the prediction of the vibration performance of the spur gear pair under different rotational conditions.

In this paper, a high-precision digital rotary encoder based on dot-matrix gratings (DMGs) is proposed for detecting shaft rotation. The DMG-based encoder is composed of a laser diode, a beam-shaping lens, a code disc, and a detector. In principle, a shaped rectangular beam illuminates a stripe of DMGs on the disc, and from the distribution of diffractive spots on the detector, the position of rotation is then decoded. Compared with a conventional geometric rotary encoder, this diffractive rotary encoder can achieve a fourfold resolution improvement.

The embryonic stem cell marker Oct4 is expressed in several human cancers and is positively correlated with a poor outcome in cancer patients. However, its physiological role in cancer progression remains poorly understood. Tumor cells block apoptosis to escape cell death so that they can proliferate indefinitely, leading to ineffective therapy for cancer patients. In this study, we investigated whether Oct4 regulates the apoptosis pathway and contributes to poor prognosis in patients with lung adenocarcinoma. Our results revealed that Oct4 expression is correlated with Stat1 expression in lung adenocarcinoma patients and Oct4 is directly bound to the Stat1 promoter to transactivate Stat1 in lung adenocarcinoma cells. Expression of the Stat1 downstream gene Mcl-1 increased in Oct4-overexpressing cancer cells, while Stat1 knockdown in Oct4-overexpressing cancer cells sensitized them to cisplatin-induced apoptosis. Furthermore, Oct4 promoted Stat1 expression and tumor growth, whereas silencing of Stat1 reduced Oct4-induced tumor growth in human lung tumor xenograft models. Taken together, we demonstrate that Oct4 is a pro-survival factor by inducing Stat1 expression and that the Oct4/Stat1/Mcl-1 axis may be a potential therapeutic target for lung adenocarcinoma.

Abstract Background Chemokines/cytokines play important roles in the pathogenesis of chronic hepatitis C (CHC). However, their clinical characteristics and implications in treatment responses to pegylated interferon plus ribavirin treatment (PegIFN/RBV) have not been fully illustrated yet. In this study, we intended to investigate the possible predictability of serum chemokines/cytokines on the treatment response in Taiwanese of CHC, genotype-1 (GT-1). Methods 60 Patients with GT-1 CHC infection who had been treated with PegIFN/RBV were enrolled, including 27 (45%) with sustained virological response (SVR), 11 (18%) with relapse after 48 weeks of treatment and 22 (37%) non-response (NR). Clinical parameters, seven chemokines/cytokines, CCL3, CCL4, CXCL9, CXCL10, CXCL11, IL-10 and IFN-γ, and genotypes of rs12979860, the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were analyzed for their relationship to treatment response. Results Baseline serum levels of CXCL10, CXCL11, CCL3 and CCL4 were significantly higher in NR group while comparing with non-NR group. (CXCL10: p = 0.001; CXCL11: p

The pathological role of vitamin K2 in Alzheimer’s disease (AD) involves a definite link between impaired cognitive functions and decreased serum vitamin K levels. Vitamin K2 supplementation may have a protective effect on AD. However, the mechanism underlying vitamin K2 protection has not been elucidated. With the amyloid-β (Aβ) cascade hypothesis, we constructed a clone containing the C-terminal fragment of amyloid precursor protein (β-CTF/APP), transfected in astroglioma C6 cells and used this cell model (β-CTF/C6) to study the protective effect of vitamin K2 against Aβ cytotoxicity. Both cellular and biochemical assays, including cell viability and reactive oxygen species (ROS), assays assay, and Western blot and caspase activity analyses, were used to characterize and unveil the protective role and mechanism of vitamin K2 protecting against Aβ-induced cytotoxicity. Vitamin K2 treatment dose-dependently decreased the death of neural cells. The protective effect of vitamin K2 could be abolished by adding warfarin, a vitamin K2 antagonist. The addition of vitamin K2 reduced the ROS formation and inhibited the caspase-3 mediated apoptosis induced by Aβ peptides, indicating that the mechanism underlying the vitamin K2 protection is likely against Aβ-mediated apoptosis. Inhibitor assay and Western blot analyses revealed that the possible mechanism of vitamin K2 protection against Aβ-mediated apoptosis might be via regulating phosphatidylinositol 3-kinase (PI3K) associated-signaling pathway and inhibiting caspase-3-mediated apoptosis. Our study demonstrates that vitamin K2 can protect neural cells against Aβ toxicity.

The purpose of signal restoration is to acquire a clean signal from the degraded signal which contains blur and noise. In this paper, a modified Tikhonov regularization method based on the standard Tikhonov regularization matrix is proposed, and the corresponding preconditioner is designed to accelerate the convergence of the proposed algorithm. The proposed method shows the best performance than several competitive methods. In addition, the convergence speed is improved significantly.

Magnetic Weyl semimetals are newly discovered quantum materials with the potential for use in spintronic applications. Of particular interest is the cubic Heusler compound Co2MnGa due to its inherent magnetic and topological properties. This work presents the structural, magnetic and electronic properties of magnetron co-sputtered Co2MnGa thin films, with thicknesses ranging from 10 to 80 nm. Polarized neutron reflectometry confirmed a uniform magnetization through the films. Hard x-ray photoelectron spectroscopy revealed a high degree of spin polarization and localized (itinerant) character of the Mn d (Co d) valence electrons and accompanying magnetic moments. Further, broadband and field orientation-dependent ferromagnetic resonance measurements indicated a relation between the thickness-dependent structural and magnetic properties. The increase of the tensile strain-induced tetragonal distortion in the thinner films was reflected in an increase of the cubic anisotropy term and a decrease of the perpendicular uniaxial term. The lattice distortion led to a reduction of the Gilbert damping parameter and the thickness-dependent film quality affected the inhomogeneous linewidth broadening. These experimental findings will enrich the understanding of the electronic and magnetic properties of magnetic Weyl semimetal thin films.

Multiple-input-multiple-output (MIMO) radar has received much attention in recent years for its great ability in imaging. However, the essence of MIMO radar has not been fully implemented due to the lack of proper transmission waveforms. In MIMO radar, the transmission waveform of each channel has to be uncorrelated with one another to avoid cross-interference between channels. To achieve this, we investigate the generation of uncorrelated multichannel chaos using electrical heterodyning for MIMO chaos radar (MIMO CRADAR) application. By electrically heterodyning a seed chaos source with multiple single-frequency local oscillators, chaos with different heterodyned spectra can be extracted and converted into multiple chaos channels. In this paper, the correlations between different channels of chaos generated are analyzed both numerically and experimentally. The minimal frequency spacing of the local oscillators for generating the largest amount of uncorrelated chaos channels is discussed. In our analysis, thousands of uncorrelated chaos channels can be simultaneously generated with a correlation time of several microseconds. Moreover, compared with those conventional waveform-designing methods that require complicated optimization and digital-to-analog conversion (DAC), the proposed heterodyned technique shows, for the first time, that multiple uncorrelated channels can be generated in real-time while breaking the bandwidth limitation of the DAC devices. A proof-of-concept experiment is successfully demonstrated to show the feasibility of using multichannel heterodyned chaos in the MIMO CRADAR application.

The goal of this presented study was to determine the optimum parameters of secondary optical elements (SOEs) for concentrated photovoltaic (CPV) units with flat Fresnel lenses. Three types of SOEs are under consideration in the design process, including kaleidoscope with equal optical path design (KOD), kaleidoscope with flat top surface (KFTS), and open-truncated tetrahedral pyramid with specular walls (SP). The function of using a SOE with a Fresnel lens in a CPV unit is to achieve high optical efficiency, low sensitivity to the sun tracking error, and improved uniformity of irradiance distribution on the solar cell. Ray tracing technique was developed to simulate the optical characteristics of the CPV unit with various design parameters of each type of SOE. Finally, an optimum KOD-type SOE was determined by parametric design process. The resulting optical performance of the CPV unit with the optimum SOE was evaluated in both single-wavelength and broadband simulation of solar spectrum.

BACKGROUND AND AIM:Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD. METHODS:A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation. RESULTS:The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0-1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3-81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis. CONCLUSIONS:PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors.

Research on digital image processing has become quite popular and rapid in recent years, and scholars have proposed various image verification mechanisms. Similarly , blockchain technology has also become very popular in recent years. This paper proposes a new image verification mechanism based on the Merkle tree technique in the blockchain. The Merkle tree root in the blockchain mechanism provides a reliable environment for storage of image features. In image verification, the verification of each image can be performed by the Merkle tree mechanism to obtain the hash value of the Merkle tree node on the path. In addition, the method combines the Inter-Planetary File System (IPFS) to improve the availability of images. The main purpose of this paper is to achieve the goal of image integrity verification. The proposed method can not only verify the integrity of the image but also restore the tampered area in the case of image tampering. Since the proposed method employs the blockchain mechanism, the image verification mechanism does not need third party resources . The verification method is performed by each node in the blockchain network. The experimental results demonstrate that the proposed method successfully achieved the goal of image authentication and tampered area restoration.

The demand for rapid online optical inspection of gear tooth surfaces is increasing, especially for precision gears. In this study, a non-contact optical measurement method was established for the inspection of gear tooth surfaces. For the system architecture, a halogen lamp was selected as the light source, and a collimated beam was produced by an autocollimator. Subsequently, moiré fringes were formed as the collimated beam went through the two linear gratings. The moiré fringes projected on the gear tooth surface were recorded with a charge-coupled device (CCD) camera, and the contour of the gear tooth surface was estimated and reconstructed from the phase information of the fringes by our developed computer codes. To verify the accuracy of the system, a spur gear tooth surface measured by a commercial coordinate measuring machine (CMM) was defined as the reference tooth profile. The tooth topography, involute profile deviation, and axial-direction deviation were successfully calculated by measuring the deviation of the optically measured surface based on the reference gear tooth profiles measured using the CMM.

A novel multi-degree-of-freedom (MDOF) microactuator was developed using a symmetric piezoelectric plate and a Ni–Co alloy micro-pusher element. A LIGA-like technique was employed to manufacture a Ni–Co alloy micro-pusher, which was then attached at the midpoint of the long side of a piezoelectric plate with dual electrodes to construct a symmetric piezoelectric pusher element (SPPE). The proposed approach integratese the concept of bricks and three different SPPE vibration modes were designed to develop a MDOF motion platform able to rotate a spherical device along three perpendicular axes. This MDOF microactuator consisted of a stator and a rotor. The stator was created from two mutually orthogonal sets of parallel SPPEs to form a MDOF motion platform, and the rotor was a spherical device. Experiments demonstrated the MDOF microactuator with working frequencies along the X, Y, and Z axes of 223.4 kHz, 223.2 kHz, and 225 kHz, respectively, and the respective rotation speeds reached 50 rpm, 52 rpm, and 180 rpm. This MODF microactuator may be used in a number of applications, such as sun-tracking systems for green energy harvesters and devices which can – eyeball-like - simultaneously and autonomously rotate along three axes for use in the biomedical field.

We examined the characteristic changes of hepatitis B virus (HBV) in antiviral drug treatment–naive patients referred for pretreatment evaluation in Taiwan during 2008–2012. Over time, we observed substantial decreases in the prevalence of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation and HBV-DNA levels in HBeAg-positive patients.

β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer's disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ.

Gramicidin A is an antimicrobial peptide that destroys gram-positive bacteria. The bactericidal mechanism of antimicrobial peptides has been linked to membrane permeation and metabolism disruption as well as interruption of DNA and protein functions. However, the exact bacterial killing mechanism of gramicidin A is not clearly understood. In the present study, we examined the antimicrobial activity of gramicidin A on Staphylococcus aureus using biochemical and biophysical methods, including hydroxyl radical and NAD+/NADH cycling assays, atomic force microscopy, and Fourier transform infrared spectroscopy. Gramicidin A induced membrane permeabilization and changed the composition of the membrane. The morphology of Staphylococcus aureus during gramicidin A destruction was divided into four stages: pore formation, water permeability, bacterial flattening, and lysis. Changes in membrane composition included the destruction of membrane lipids, proteins, and carbohydrates. Most interestingly, we demonstrated that gramicidin A not only caused membrane permeabilization but also induced the formation of hydroxyl radicals, which are a possible end product of the transient depletion of NADH from the tricarboxylic acid cycle. The latter may be the main cause of complete Staphylococcus aureus killing. This new finding may provide insight into the underlying bactericidal mechanism of gA.

The aim of this study was to develop a simple and reliable high-performance chromatographic (HPLC) method for simultaneous analysis of adapalene and benzoyl peroxide in pharmaceutical formulation by response surface methodology (RSM). An optimized mobile phase composed of acetonitrile, tetrahydrofuran and water containing 0.1% acetic acid at a ratio of 25:50:25 by volume was successfully predicted by using RSM. An isocratic separation was achieved by using the condition. Furthermore, the analytical method was validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentration. Finally, the method was successfully applied to the analysis of a commercial product.

This paper presents the results of a parametric design process used to achieve an optimal secondary optical element (SOE) in a noncoplanar solar concentrator composed of two reflectors. The noncoplanar solar concentrator comprises a primary parabolic mirror (M1) and a secondary hyperbolic mirror (M2). The optical performance (i.e., acceptance angle, optical efficiency, and irradiance distribution) of concentrators with various SOEs was compared using ray-tracing simulation. The parametric design process for the SOE was divided into two phases, and an optimal SOE was obtained. The sensitivity to assembly errors of the solar concentrator when using the optimal SOE was studied and the findings are discussed.

Inflammation has significant impacts on liver fibrosis measurement by ultrasound elastography. The interpretation requires further optimization in patients with or without anti-viral therapy. We prospectively enrolled a consecutive series of patients with chronic hepatitis B who received liver histology analysis and acoustic radiation force impulse (ARFI). 146 patients who underwent liver biopsy (50.9%) or tumor resection (49.1%) were enrolled. 34 patients (23.3%) had been receiving anti-hepatitis B therapy of various duration. The areas under the receiver-operating characteristic (AUROC) for the diagnosis of Metavir F4 by mean ARFI was 0.820 in the non-treatment group and 0.796 in the treatment group. The ARFI tended to be not lower (100%) than the corresponding Metavir grading in patients with treatment within 12 months, equal (75%) from 13 to 31 months, and lower (71.4%) after 32 months. We conclude that ARFI is a reliable tool for measurement of liver fibrosis in chronic hepatitis B patients with ALT (alanine aminotransferase)

Many properties of Aβ such as toxicity, aggregation and ROS formation are modulated by Cu2+. Previously, the coordination configuration and interaction of Cu2+ with the Aβ N-terminus has been extensively studied. However, the effect of Aβ C-terminal residues on related properties is still unclear. In the present study, several C-terminus-truncated Aβ peptides, including Aβ1-40, Aβ1-35, Aβ1-29, Aβ1-24 and Aβ1-16, were synthesized to characterize the effect of Aβ C-terminal residues on Cu2+ binding affinity, structure, aggregation ability and ROS formation. Results show that the Aβ C-terminal residues have effect on Cu2+ binding affinity, aggregation ability and inhibitory ability of ROS formation. Compared to the key residues responsible for Aβ aggregation and structure in the absence of Cu2+, it is more likely that residues 36-40, rather than residues 17-21 and 30-35, play a key role on the related properties of Aβ in the presence of Cu2+.

Collimator design is essential for meeting the requirements of high-precision telescopes. The collimator diameter should be larger than that of the target for alignment. Special supporting structures are required to reduce the gravitational deformation and control the surface deformation induced by the mounting force when inspecting large-aperture primary mirrors (M1). A ZERODURÂŽ mirror 620 mm in diameter for a collimator was analyzed using the finite element method to obtain the deformation induced by the supporting structures and adjustment mechanism. Zernike polynomials were also adopted to fit the optical surface and separate corresponding aberrations. The computed and measured wavefront aberration configurations for the collimator M1 were obtained complementally. The wavefront aberrations were adjusted using fine adjustment screws using 3D optical path differences map of the mirror surface. Through studies using different boundary conditions and inner ring support positions, it is concluded that the optical performance was excellent under a strong enough supporter. The best adjustment position was attained and applied to the actual collimator M1 to prove the correctness of the simulation results.

The paper aims at obtaining the optimum lightweight configuration for a primary mirror (M1) with honeycomb patterns for a space satellite. The finite element analysis and Zernike polynomial fitting based on the Taguchi Method are applied to the whole optimization process. Geometrical control factors and levels were selected to minimize the ratio of various mass reduction ratios (MRRs) to the product of the corresponding maximum mirror structural deflection and optical surface peak-to-valley wavefront aberrations under launch accelerations. The optimum lightweight M1 with a MRR of 0.5 and a mass of 9.72 kg is attained and a mirror blank based on this design was manufactured. The performance of the optimum lightweight mirror is simulated and the simulation results satisfy the requirements of space specifications.

Alzheimer's disease is the most common form of neurodegenerative disease. Beta-amyloid peptides (Aβ) are responsible for neuronal death both in vitro and in vivo. Previously, L17 and F19 residues were identified as playing key roles in the stabilization of the Aβ40 conformation and in the reduction of its neurotoxicity. In this study, the effects of L17A/F19A mutations on the neurotoxicity of Aβ genetic mutant Arctic-type Aβ40(E22G) were tested. The results showed that compared to Aβ40(E22G), Aβ40(L17A/F19A/E22G) reduced the rate of conformation conversion, aggregation, and cytotoxicity, suggesting that L17 and F19 are critical residues responsible for conformational changes which may trigger the neurotoxic cascade of Aβ. Aβ40(L17A/F19A/E22G) also had decreased damage due to reactive oxygen species. The results are consistent with the discordant helix hypothesis, and confirm that residues 17-25 are in the discordant helix region. Compared to Aβ40(L17A/F19A), reduction in aggregation of Aβ40(L17A/F19A/E22G) was less significantly decreased. This observation provides an explanation based on the discordant helix hypothesis that the mutation of E22 to G22 of Aβ40(E22G) alters the propensity of the discordant helix. Arctic-type Aβ40(E22G) aggregates more severely than wild-type Aβ40, with a consequential increase in toxicity.

BACKGROUND: Recent research shows that visible-light responsive photocatalysts have potential usage in antimicrobial applications. However, the dynamic changes in the damage to photocatalyzed bacteria remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Facilitated by atomic force microscopy, this study analyzes the visible-light driven photocatalyst-mediated damage of Escherichia coli. Results show that antibacterial properties are associated with the appearance of hole-like structures on the bacteria surfaces. Unexpectedly, these hole-like structures were preferentially induced at the apical terminus of rod shaped E. coli cells. Differentiating the damages into various levels and analyzing the percentage of damage to the cells showed that photocatalysis was likely to elicit sequential damages in E. coli cells. The process began with changing the surface properties on bacterial cells, as indicated in surface roughness measurements using atomic force microscopy, and holes then formed at the apical terminus of the cells. The holes were then subsequently enlarged until the cells were totally transformed into a flattened shape. Parallel experiments indicated that photocatalysis-induced bacterial protein leakage is associated with the progression of hole-like damages, further suggesting pore formation. Control experiments using ultraviolet light responsive titanium-dioxide substrates also obtained similar observations, suggesting that this is a general phenomenon of E. coli in response to photocatalysis. CONCLUSION/SIGNIFICANCE: The photocatalysis-mediated localization-preferential damage to E. coli cells reveals the weak points of the bacteria. This might facilitate the investigation of antibacterial mechanism of the photocatalysis.

BACKGROUND: The need for efficient algorithms to uncover biologically relevant phosphorylation motifs has become very important with rapid expansion of the proteomic sequence database along with a plethora of new information on phosphorylation sites. Here we present a novel unsupervised method, called Motif Finder (in short, F-Motif) for identification of phosphorylation motifs. F-Motif uses clustering of sequence information represented by numerical features that exploit the statistical information hidden in some foreground data. Furthermore, these identified motifs are then filtered to find "actual" motifs with statistically significant motif scores. RESULTS AND DISCUSSION: We have applied F-Motif to several new and existing data sets and compared its performance with two well known state-of-the-art methods. In almost all cases F-Motif could identify all statistically significant motifs extracted by the state-of-the-art methods. More importantly, in addition to this, F-Motif uncovers several novel motifs. We have demonstrated using clues from the literature that most of these new motifs discovered by F-Motif are indeed novel. We have also found some interesting phenomena. For example, for CK2 kinase, the conserved sites appear only on the right side of S. However, for CDK kinase, the adjacent site on the right of S is conserved with residue P. In addition, three different encoding methods, including a novel position contrast matrix (PCM) and the simplest binary coding, are used and the ability of F-motif to discover motifs remains quite robust with respect to encoding schemes. CONCLUSIONS: An iterative algorithm proposed here uses exploratory data analysis to discover motifs from phosphorylated data. The effectiveness of F-Motif has been demonstrated using several real data sets as well as using a synthetic data set. The method is quite general in nature and can be used to find other types of motifs also. We have also provided a server for F-Motif at http://f-motif.classcloud.org/, http://bio.classcloud.org/f-motif/ or http://ymu.classcloud.org/f-motif/.