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We administered Ad26, modified vaccinia Ankara vectors containing mosaic HIV-1 antigens or placebo in 26 individuals who initiated antiretroviral therapy during acute human immunodeficiency virus infection as an exploratory study to determine the safety and duration of viremic control after treatment interruption. The vaccine was safe and generated robust immune responses, but delayed time to viral rebound compared to that in placebo recipients by only several days and did not lead to viremic control after treatment interruption (clinical trial NCT02919306).

Nutrient utilization and energy metabolism are critical for the maintenance of cellular homeostasis. A mutation in the C9orf72 gene has been linked to the most common forms of neurodegenerative diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we have identified an evolutionarily conserved function of C9orf72 in the regulation of the transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes that is negatively modulated by mTORC1. Loss of the C. elegans orthologue of C9orf72, ALFA-1, causes the nuclear translocation of HLH-30/TFEB, leading to activation of lipolysis and premature lethality during starvation-induced developmental arrest in C. elegans. A similar conserved pathway exists in human cells, in which C9orf72 regulates mTOR and TFEB signaling. C9orf72 interacts with and dynamically regulates the level of Rag GTPases, which are responsible for the recruitment of mTOR and TFEB on the lysosome upon amino acid signals. These results have revealed previously unknown functions of C9orf72 in nutrient sensing and metabolic pathways and suggest that dysregulation of C9orf72 functions could compromise cellular fitness under conditions of nutrient stress., Author summary An expansion of repeated nucleotides in the non-coding region of the C9orf72 gene has been linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion leads to a reduced expression of the C9orf72 gene and loss of function of the C9orf72 protein may contribute to the pathogenesis. In this study, we identified a new mechanism through which C9orf72 influences nutrient sensing, autophagy, and metabolism. In the multi-cellular organism Caenorhabditis elegans, the C9orf72 orthologue regulates the activity of TFEB, a crucial transcriptional regulator of autophagic and lysosomal genes, through which the lipid metabolism and survival are influenced especially under nutrient stress conditions. The regulatory effect of C9orf72 on TFEB is conserved in mammals, and this is mediated by the dynamic regulation of the Rag GTPases by C9orf72. Given the critical role of the Rag GTPases in nutrient sensing and autophagy, we propose that the C9orf72 function is important for metabolic homeostasis in the cell and its deficiency can lead to compromised fitness under stress conditions.

BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX® B/E administration over six months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunologic impact of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomized clinical trial conducted in three clinical sites in Thailand. HIV-uninfected volunteers aged 20–40 randomly received the primary RV144 vaccine series at months 0, 1, 3, and 6, with no additional boost (Group I), additional AIDSVAX® B/E and ALVAC-HIV (vcp1521) at month 12 (Group II), AIDSVAX® B/E alone at month 12 (Group III), AIDSVAX® B/E and ALVAC-HIV at month 15 or 18 (Groups IVa or IVb), or placebo and were followed for 24 months. A randomization schedule was centrally generated with fixed sized strata for RIHES Chiang Mai (n=60) and combined Bangkok clinics (n=300). Primary outcomes were to assess the safety and tolerability of these vaccination regimens and characterize and compare cellular and humoral immune responses between the RV144 series alone and late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. Primary immunogenicity outcomes were evaluated by comparing peak humoral responses (HIV-specific IgG and IgA ELISA) and cellular responses (HIV-specific intracellular cytokine staining and polyfunctionality) two weeks post final vaccination among per-protocol participants who completed all vaccinations. This trial is registered at (ClinicalTrials.gov (NCT01931358); clinical follow up is now complete. FINDINGS: Between 28 October 2013 and 29 April 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in Group I, 102 in Group II, 101 in Group III, 52 in Group IVa, 51 in Group IVb, and 34 combined placebo across all groups. Late boosting did not induce vaccine-related serious adverse events. There were no significant differences in the occurrence or severity of local or systemic reactogenicity across active groups. Groups with late boosts (Groups II, III, IVa, and IVb) had increased peak plasma IgG binding antibody levels against gp70 V1V2 relative to Group I vaccine recipients with no late boost (gp70V1V2 92TH023 adjusted p < 0·02 for each; gp70V1V2 Case A2 adjusted p month 15 (Group IVa) > month 12 (Groups II+III) > no late boost (Group I). Groups with late boosts had increased both functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p < 0·05, except for polyfunctionality score in Group I vs in Group IVb p < 0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and may improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of the Army.

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality., Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

This paper studies platform ecosystems, which refer to a novel solution built upon a platform coordinating business interactions between suppliers and users, particularly in the IT service sectors....

The micronutrient selenium is incorporated via the selenocysteine biosynthesis pathway into the rare amino acid selenocysteine, which is required in selenoproteins such as glutathione peroxidases and thioredoxin reductases1,2. Here, we show that selenophosphate synthetase 2 (SEPHS2), an enzyme in the selenocysteine biosynthesis pathway, is essential for survival of cancer, but not normal, cells. SEPHS2 is required in cancer cells to detoxify selenide, an intermediate that is formed during selenocysteine biosynthesis. Breast and other cancer cells are selenophilic, owing to a secondary function of the cystine/glutamate antiporter SLC7A11 that promotes selenium uptake and selenocysteine biosynthesis, which, by allowing production of selenoproteins such as GPX4, protects cells against ferroptosis. However, this activity also becomes a liability for cancer cells because selenide is poisonous and must be processed by SEPHS2. Accordingly, we find that SEPHS2 protein levels are elevated in samples from people with breast cancer, and that loss of SEPHS2 impairs growth of orthotopic mammary-tumour xenografts in mice. Collectively, our results identify a vulnerability of cancer cells and define the role of selenium metabolism in cancer.

This study analyses the core changes in the entire industrial structure of China from 2002 to 2015. First, utilizing the input–output model (or interindustry relation model), we evaluate the production-inducing effects across the various manufacturing and service sectors. Employing standard centrality measures that are often used in network analysis, we identify the status of various industry sectors together with their structural roles on the input–output network and track the evolutionary paths as they change over time. Furthermore, the clustering analysis of industrial sectors also examines critical changes in the overall industrial structure. We will discuss the policy implications of these evolutionary paths and explore the trends and sources of Chinese economic development regarding manufacturing and service productions. As a result, it can be seen that the production-inducing effects in the manufacturing sectors—particularly, chemical, electric power, and primary metal products—play the core role in driving the economy. On the other hand, the distribution sector like the traditional wholesale and retail services still shows unstable connections with other industries. However, the sectors like finance and transportation, which constitute another axis of the service industry, have strengthened their connection with the manufacturing sectors since 2012. Moreover, the real estate and lease and the other business support services continue to absorb production resources, deepen their linkages with the key service industries (e.g., transportation), and the various manufacturing sectors. In conclusion, China still has manufacturing as a central driving force for economic development, but with the increasing integration with the service sectors, both manufacturing and service industries show an apparent convergence in their production activities.

This study explored the possibility of using reverse osmosis (RO) reject water as a mixing water for producing cementitious bricks using calcium sulfoaluminate (CSA) cement along with gypsum, and it investigated the changes in the properties of CSA cement pastes when RO reject water was used. The results were compared with those obtained using purified water and seawater. Overall, the use of RO reject water improved the cement paste&rsquo, s strength. Given that the use of RO reject water very slightly affected ettringite formation but more significantly influenced the Al2O3-Fe2O3-mono (AFm) phases (i.e., monosulfate, kuzelite, and Friedel&rsquo, s salt) and amorphous aluminum hydroxide (AH3), the strength improvement was likely mainly due to the formation of Friedel&rsquo, s salt rather than ettringite formation. This study also demonstrated that the use of RO reject water for brick production satisfied the Korean Standards (KS) F 4004 and toxicity characteristic leaching procedure (TCLP), thus, it is recommended to use RO reject water as a mixing water to produce CSA cement bricks for use in construction.

Attackers use the openness of the Internet to facilitate the dissemination of malware. Their attempts to infect target systems via the Web have increased with time and are unlikely to abate. In response to this threat, we present an automated, low-interaction malicious webpage detector, WebMon , that identifies invasive roots in Web resources loaded from WebKit2-based browsers using machine learning and YARA signatures. WebMon effectively detects hidden exploit codes by tracing linked URLs to confirm whether the relevant websites are malicious. WebMon detects a variety of attacks by running 250 containers simultaneously. In this configuration, the proposed model yields a detection rate of 98%, and is 7.6 times faster (with a container) than previously proposed models. Most importantly, WebMon ’s focus on extracting malicious paths in a domain is a novel approach that has not been explored in previous studies.

This paper presents a pulse radar system to detect drones based on a target fluctuation model, specifically the Swerling target model. Because drones are small atypical objects and are mainly composed of non‐conducting materials, their radar cross‐section value is low and fluctuating. Therefore, determining the target fluctuation model and applying a proper integration method are important. The proposed system is herein experimentally verified and the results are discussed. A prototype design of the pulse radar system is based on radar equations. It adopts three different pulse modes and a coherent pulse integration to ensure a high signal‐to‐noise ratio. Outdoor measurements are performed with a prototype radar system to detect Doppler frequencies from both the drone frame and blades. The results indicate that the drone frame and blades are detected within an instrumental maximum range. Additionally, the results show that the drone's frame and blades are close to the Swerling 3 and 4 target models, respectively. By the analysis of the Swerling target models, proper integration methods for detecting drones are verified and can thus contribute to increasing in detectability.

This paper presents a novel polyphase-basis discrete cosine transform that can be used for challenges to observe heart rate (HR) variability and sudden changes of HR in short time. To succeed in the challenges, real-time measurement which requires a short window length is needed. As the window length decreases, however, increased main-lobe width (MLW) and sidelobe width (SLW) result errors in measuring HR. Unlike commonly used discrete Fourier transform (DFT), the proposed method is based on DCT, which improves the accuracy of measured HR even though the short window length is used for the real-time measurement of HR. We demonstrate that the DCT can give 2 times shorter MLW and SLW than the DFT can. To verify the proposed method, it is compared with well-known existing methods, arctangent demodulation and complex signal demodulation, which use the DFT. We measured HR using a 10.225-GHz continuous-wave Doppler radar. In each experiment, the window lengths of 3, 2, and 1.5 s were used to measure HR in real time. Experimental results show that the proposed method has lower mean and standard deviation of errors than the existing methods have.

Rural labor force has been gradually decreased due to decreasing of farm population and increasing of aging population. Therefore, the study of unmanned technology is needed to overcome labor shortage in agriculture. These days most research on unmanned autonomous tractors has been carried out through field tests; however, field tests require lots of cost and time. Therefore, in this study, a simulation platform model was developed for the driving performance evaluation of unmanned tractors. Simulation was conducted by using analysis tools which used widely in the testing of unmanned vehicle simulation and vehicle dynamic behavior. Tractor model used in the simulation was a 71 kW-class (L7040, LS Mtron, Korea). Simulation was conducted to evaluate autonomous driving performance based on driving paths and field conditions. The results of the simulation showed that larger values in the error of tire force, tire kinematics, and slip were observed at the curved path than at the straight path. In the future study, it is determined that need for a method for reducing a positioning error through control algorithm developed at the curved paths.

Porous silicon nanowires (PSi NWs) responding to red, green and blue lights simultaneously are reported in this study. NWs with a diameter of 120 nm were prepared from p-type Si wafer by metal-catalyst-assisted etching. The NWs produced in this manner had an outer porous region consisting of Si nanocrystals small enough to ensure the quantum confinement effect. Hydrazine treatment passivated the porous region by reduction of the surface oxides and the formation of Si-H bonds. The energy band structure of the porous region was a direct transition type, while the emission/absorption energies corresponded to red (1.94 eV), green (2.24 and 2.44 eV) and blue (2.98 eV) light photons. A device structure prepared by suspending 10 PSi NWs between two Al electrodes by dielectrophoresis generated photocurrents upon exposure to red, green and blue lights. The rising and decay times were both 30 μs and the ratio of photocurrent to dark current was 92.0, 59.8 and 24.4 for the blue, green and red lights, respectively. The device could be bent down to the bending radius of 5 mm without any significant deterioration of the photoresponse performances. Further, the device survived repeated bending and unbending over 10 000 cycles with this bending radius, demonstrating its application potential as a flexible device with multiple-wavelength photosensing capabilities.

This study explored the influence of using copper slag as an alternative sand for producing cement mortar bricks and its effect on γ-ray attenuation property, strength, and consistency of mortar. The linear attenuation coefficients and mass attenuation coefficients were experimentally determined for mortar mixtures using the 60Co and 137Cs gamma-ray source, and, using the Phy-X program, attenuation parameters were theoretically calculated in 1 keV–100 GeV. Sample bricks with added copper slag were produced and tested. In the results, the added copper slag was greatly beneficial for increasing the flowability and strength of mortar, and, given all the results of attenuation parameters, the use of copper slag as aggregates was notably advantageous compared to silica sands for gamma-ray attenuation mainly due to the high Fe quantity in copper slag. The trial brick specimens using 100 wt% copper slag replacement for sand not only satisfied all requirements of cement brick in the Korean standard (KS) F 4004, but also the TCLP regulation.

The robot sector in many countries has thrived recently thanks to government supports and innovations in various industries. This study, using the patent database to define the robot sector, reconfigures IO (Input-Output) data to analyze the relationships among various sectors. In particular, we consider the internal description of the robot sector (mesoscopic view) as well as the relationship between the robot and the non-robot sectors (macroscopic view), so that we can not only understand robot ecosystems in various dimensions, but also develop policy insights. For the sake of systematic analysis of the intra- and inter-sector relations as well as the meso-macro links, this study constructs network models and employs several network measures. Our model and analysis present a good case study of Korea to understand the nature of the robot sector and the overall business ecosystem there. This novel approach also contributes to finding out a promising path that leverages the strengths of intra-sector relations and spreads the impact of the robot sector across the macro relations.

This study investigated the role of crystallinity of added nanometer-sized Al2O3 (nano-alumina) (i.e., poorly crystalline nano-alumina (γ-alumina) vs. crystalline nano-alumina (α-alumina)) and the interaction of nano-aluminas with added gypsum in the CaO-activated ground granulated blast furnace slag (GGBFS) binder system. In the results, the use of γ-alumina evidently increased the dissolution degree of silicon (Si) from GGBFS regardless of adding gypsum, which was the main ingredient of calcium silicate hydrate (C-S-H), and thus led to a noticeable increase of C-S-H. However, the sole use of α-alumina without added gypsum barely affected the C-S-H formation, although the added α-alumina alongside gypsum also had a similar effect on the dissolution of Si. In addition, due to the amorphous nature of γ-alumina, the dissolution of γ-alumina was faster than that of α-alumina. Thus, the use of γ-alumina produced ettringite at the faster rate, as well achieving the greater and faster strength increase, although the added α-alumina was also slightly beneficial in accelerating the formation of ettringite. Thus, overall, the use of γ-alumina was significantly more advantageous in improving strength by increasing the quantities of reaction products (C-S-H and/or ettringite) than that of α-alumina.

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

Background: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX® B/E administration over six months resulted in a 31% efficacy in preventing HIV acquisition. Subsequent boosting of RV144 vaccine recipients 6 to 8 years later improved the magnitude and quality of immune responses, expanding subdominant memory B cells. Methods: RV306 is a double-blind, placebo-controlled, randomized clinical trial of the primary RV144 vaccine series with additional AIDSVAX® B/E with or without ALVAC-HIV boosting at months 12, 15, or 18 in healthy volunteers. Findings: Late boosting was safe, and improved antigen-specific plasma IgG responses to HIV-1 envelope and the first and second variable loops (V1V2), an inverse correlate of HIV risk in RV144, without increasing HIV-specific plasma IgA, a direct correlate of risk. Late boosting improved Tier 1 neutralization and HIV-1 envelope-specific CD4+ T cell polyfunctionality, an independent correlate contributing to RV144 vaccine efficacy. Late boosting was also required to maintain antigen-specific CD4+ T cell proliferation. Interestingly, increasing the interval between priming and boosting improved several humoral and cellular immune responses. Interpretation: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and may improve the efficacy of preventing HIV acquisition. Funding Statement: Cooperative Agreement # W81XWH-18-2-0040 in collaboration with the US Army and DAIDS/NIAID/NIH. Declaration of Interests: J. T., and C. D. are employees of Sanofi Pasteur. S.P. was an employee of Sanofi Pasteur during the conduct of this study and analysis. F. S. is an employee of Global Solutions for Infectious Diseases. All other authors report no potential conflicts. The opinions expressed herein are those of the authors and do not represent the official position of the US Army or the Department of Defense. Trade names are used for identification purposes only and do not imply endorsement. Ethics Approval Statement: The study was approved by ethical review boards at the Walter Reed Army Institute of Research, Thai Ministry of Public Health, Royal Thai Army Medical Department, Faculty of Tropical Medicine, Mahidol University, Chiang Mai University, and Chulalongkorn University Faculty of Medicine. This study was conducted in accordance with Good Participatory Practice principles.

To test whether sulpiride (SP), an anti-psychotic and prokinetic drug, shows beneficial effects on experimental murine colitis, a colon-targeted prodrug of SP, 5-(aminoethanoylsulfamoyl)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxybenzamide (glycylsulpiride (GSP)), was synthesized and its colonic delivery and therapeutic activity against 2,4-dinitrobenzenesulfonic acid (DNBS)–induced rat colitis were assessed. Synthesis of GSP was verified by infrared and proton nuclear magnetic resonance spectroscopy. GSP was converted to SP when incubated with the cecal contents but not when incubated with the small intestinal contents. The percent conversion was about 50.5% at 6 h and 67.7% at 10 h. Colonic delivery of GSP was examined by comparison with sulfasalazine (SSZ), a colon-specific prodrug of 5-aminosalicylic acid currently used for the treatment of inflammatory bowel disease. The two prodrugs accumulated similar concentrations of the corresponding parent drugs in the cecum at 2, 4, and 6 h after oral gavage. Although oral gavage of GSP released millimolar level of SP in the large intestine, SP was hardly detected in the blood. GSP improved colonic damage score and reduced myeloperoxidase activity up to 80.5% in the inflamed colon in a dose-dependent manner. Moreover, GSP was able to reduce the levels of inflammatory mediators in the inflamed colon. Overall, the anti-colitic effectiveness of GSP and SSZ was similar. In conclusion, colonic delivery of SP ameliorates DNBS-induced colitis in rats with no significant systemic absorption of SP. Thus, colon-targeted SP may be therapeutically switched to an anti-colitic drug.

CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

The ionic crystals of perovskites have been widely studied for light-emitting diodes (LEDs) applications because their optical bandgap can be adjusted by changing the composition of the halide anions. However, the small ion size of Cs+ in inorganic perovskite causes poor crystallinity and a low exciton binding energy owing to the inherent defects in the bulk perovskite, which hinder the luminescence efficiency of perovskite LEDs (PeLEDs). Moreover, cesium lead iodide (CsPbI3), which is studied as an emitter of red PeLEDs, is not only required to be heat-treated at a high temperature of 300 °C for phase stabilization but also vulnerable to O2 and moisture in the air. To solve these problems, high performance red PeLED based on CsPbBr0.6I2.4 perovskites were fabricated by using poly(2-ethyl-2-oxazoline) (PEOXA) as a hydrophilic polymer. This method reduced the transition temperature of CsPbBr0.6I2.4 from the δ–phase (tilted octahedral) to the α–phase (cubic) and stabilized the perovskite phase. Thus, an exceptionally efficient and stable PeLED based on a CsPbBr0.6I2.4–45% PEOXA film with a maximum external quantum efficiency (EQE) of 5.4%, luminance of 201.2 cd/m2, and current efficiency (CE) of 3.2 cd/A was fabricated. Moreover, the PeLED exhibited a low turn-on voltage (1.5 V) and CIE coordinates of (0.726, 0.274), with pure-red emission.

Escherichia coli cells with autodisplayed Z-domains have been used for immunoassays of specific target analytes. In this study, a magnetite suspension was used for the washing step in immunoassays of E. coli cells with autodisplayed Z-domains. This approach enhanced the washing conditions for these immunoassays by determining (1) the optimal concentration of the magnetite suspension, (2) the capacity of the magnetite suspension-based washing method to recover E. coli cells, and (3) the level at which the activity of autodisplayed Z-domains is maintained. In immunoassays of C-reactive protein (CRP), the immunoassay incorporating the magnetite suspension-based washing method showed a sensitivity and limit of detection considerably higher than those of the conventional centrifugation-based washing method. The results indicated that immunoassays incorporating the magnetite suspension-based washing method are effective for medical diagnoses based on CRP assay.

In this work, the selenization of Mo/CuGa/In/Se (Se layer thickness: 1 μm) precursors followed by sulfurization was investigated. Particular emphasis was placed on the effect of the variation of the selenization temperature and sulfurization time on the morphology and compositional depth profiles of the resulting Cu(InGa)(SeS)2 (CIGSS) absorber; in addition, the current-voltage characteristics of the corresponding devices were investigated. The selenization of the precursors was achieved by using a tube-type rapid thermal annealing system at various temperatures (500, 550, and 600 °C). Post-sulfurization of Cu(InGa)Se2 (CIGS) was performed in the same system by flowing H2S/He gas at 600 °C for different periods of time (5, 10, and 15 min). Post-sulfurization can improve the open-circuit voltage of a solar cell by attracting Ga toward the surface region of the light absorber and incorporating S into the absorber to yield quinary CIGSS compounds. In addition, the voids at the Mo/CIGS interface, produced during the selenization of the CuGa/In/Se precursors, were effectively removed after post-sulfurization. Among the process conditions explored in this study, the selenization of Mo/CuGa/In/Se at 550 °C for 7 min followed by sulfurization at 600 °C for 10 min produced the device with the best performance, providing also good material properties in terms of morphology and compositional homogeneity.

A simple strategy, based on the Al-doped ZnO nanorods (NRs), to get an antireflective, self-cleanable and electrical conductive window layer for the thin film solar cell was demonstrated. The length and diameter of Al-doped ZnO NRs were optimized by controlling Al precursor concentration and growth time and an average reflectance of 2.9% was achieved. Al-doped ZnO NRs simultaneously having the rugged surface morphology with the micrometer- and nanometer-scale roughness also exhibited superhydrophobicity and extremely small water contact angle (WCA) hysteresis below Δ1° after treatment of hydrophobic self-assembled monolayer (SAM). Finally, in spite of the existence of the SAM, the enhancement of the electrical contact with silver from Schottky to Ohmic for various Al doping concentrations was confirmed. Self-cleanable and electrically conductive antireflecting layer introduced in this work would be expected to increase photovoltaic efficiency in a thin film solar cell.

The Z-domain has the potential to control the orientation of immobilized antibodies because of its binding affinity to the Fc regions of antibodies (IgGs). In this work, Z-domains were autodisplayed on the outer membrane (OM) of Escherichia coli. OM particles were isolated and coated onto microbeads with positive, neutral, or negative surface charges. Other conditions such as incubation time and initial OM concentration were also optimized for the OM coating to obtain maximum antibody-binding. Using three kinds of model proteins with different isoelectric points (pI), streptavidin (pI = 5, negative charge at pH 7), horseradish peroxidase (pI = 7, neutral charge at pH 7), and avidin (pI = 10, positive charge at pH 7), protein immobilization onto the microbeads was carried out through physical adsorption and electrostatic interactions. Using fluorescently labeled antibodies and fluorescence-activated cell sorting, it was determined that the neutral and the positively charged microbeads effectively bound antibodies while minimizing non-specific protein binding. The OM-coated microbeads with autodisplayed Z-domains were applied to C-reactive protein immunoassay. This immunoassay achieved 5-fold improved sensitivity compared to conventional immunoassay based on physical adsorption of antibodies at the cutoff concentration of medical diagnosis of inflammatory diseases (1000 ng/ml) and cardiovascular diseases (200 ng/ml).

Flexible multi-channel Si nanowire (NW) field-effect transistors (FETs) were investigated to determine the effect of the number of Si NWs. The Langmuir-Blodgett method was applied for the formation of well-aligned Si NW monolayers, and an ion-gel with a high dielectric constant was used as a gate insulator in a top-gate TFT structure to secure flexibility. Like typical nanoelectronic devices, the drain current changed with the number of Si NWs. However, unlike previous reports, the mobility of the multi-channel Si NW FETs increased from 42.8 to 124.6 cm(2) V(-1) s(-1) as the number of Si NWs was increased from 1 to 58. To verify the feasibility of our approach, the electrical performance of the TFTs fabricated on a flexible polyimide (PI) substrate was analyzed in respect of the bending strain (0.08-1.51%) and bending cycle (up to 12 000 cycles). As the number of Si NWs was increased, the trade-off between electrical and mechanical properties during bending tests was confirmed, and the appropriate number of Si NWs was optimized for a flexible FET with excellent performance.

This study sought to evaluate the effects of Phaseolus multiflorus var. albus Bailey extract (PM extract) and Pleurotus eryngii var. ferulae extract (PF extract) on the inhibition of digestive enzymes and to confirm the anti-obesity effect of DKB-117 (a mixture of PM extract and PF extract) in digestive enzyme inhibition in a mouse model of obesity induced by a high-fat diet. In in vitro studies, PM extract and PF extract have increased dose-dependent inhibitory activity on &alpha, amylase (Inhibitory concentration (IC50 value: 6.13&thinsp, mg/mL)) and pancreatic lipase (IC50 value, 1.68&thinsp, mg/mL), respectively. High-fat diet&ndash, induced obese mice were orally administered DKB-117 extracts at concentrations of 100, 200, and 300 mg/kg/day, while a positive control group was given orlistat (pancreatic lipase inhibitor) and Garcinia cambogia (inhibiting the enzymes needed to synthesize carbohydrates into fat) at concentrations of 40 and 200 mg/kg/day, respectively, for eight weeks. As a result, body weight, fat mass (total fat mass, abdominal fat, and subcutaneous fat) detected with microcomputed tomography, fat mass (abdominal fat and inguinal fat) after an autopsy, and liver triglyceride levels were decreased significantly in the DKB-117 (300 mg/kg/day) group compared to those in the HFD control group. Additionally, we obtained results indicating that the presence of carbohydrates was found more in the DKB-117-300 (300 mg/kg/day) group than in the HFD control group. These data clearly show that DKB-117 extracts are expected to have an anti-obesity effect through a complex mechanism that promotes carbohydrate release through the inhibition of carbohydrate-degrading enzymes while blocking lipid absorption through lipase inhibition.

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.

Recently, the combined use of calcium oxide (CaO) and calcium formate (Ca(HCOO)2) has been proposed as an alternative activator for ground granulated blast furnace slag (GGBFS) (referred to as CaO-Ca(HCOO)2-activated GGBFS system). However, this clinker-free binder system produces calcium aluminate hydrate (C2AH8), generally leading to the degradation of cementitious binder systems by its conversion to other phases. Thus, in this study, attempts to remove C2AH8 from this system without losing the strength are suggested by the use of two additives (i.e., calcium sulfate (CaSO4) and calcium nitrate (Ca(NO3)2), respectively). Results revealed that the above-mentioned additives completely remove C2AH8 in the initial curing stage via its conversion to ettringite or NO3- and NO2-AFm, respectively. In addition, the additives reduced the extent of the total shrinkage and the standard deviation of strength results of triplicate samples. However, CaSO4 exerted a beneficial effect on the strength, while Ca(NO3)2 exerted a marginal or detrimental effect on the strength. Therefore, this study suggested a new mixture form of an activator, comprising CaO, Ca(HCOO)2, and CaSO4, to activate GGBFS for maintaining strength without the conversion issue of C2AH8.

In this study, a new clinker-free white binder that exhibits whiteness comparable to that of white Portland cement was proposed by investigating the effects of an activator (i.e., CaO vs. NaOH) and added TiO2 (i.e., anatase vs. rutile, dosage) on the surface colors of activated ground granulated blast furnace slag (GGBFS). Overall, compared to the type or dosage of TiO2, the type of activator exhibited a more pronounced effect on the surface color although TiO2 was considerably beneficial for increasing whiteness. As determined by ASTM E313, the results revealed that all NaOH-activated samples are neither “white” nor “near white,” even with the highest dosage of the added TiO2, while all CaO-activated samples were nearly white even without the added TiO2. In addition, NaOH and CaO produced different tints (i.e., green by NaOH and red by CaO activation, respectively) regardless of the presence of TiO2. In CaO activation, rutile was more effective than anatase in improving all color indices and whiteness; however, in NaOH activation, the addition of anatase was better for reducing tints of yellowness and greenness. The whitest sample was obtained, which was whiter than white Portland cement on all days, by the addition of 16% rutile in CaO activation; however, if strength was considered in addition to whiteness, the same system with 4 wt% rutile would be the best candidate mixture.

Mucosal associated invariant T (MAIT) cells are an unconventional T cell subset with a semi-invariant TCR that recognizes microbially-derived riboflavin metabolites and elicit broad antimicrobial activity. MAIT cells are implicated in the control of bacterial infections, however, their role in enterotoxigenic E. coli (ETEC) infection, a common cause of traveler’s diarrhea, is unknown. Using multi-color polychromatic flow cytometry and RNA-seq on sorted peripheral MAIT cells of volunteers orally challenged with ETEC strains H10407 (CFA/I+LT+ST+; median time to first loose stool, mtFLS=47h; n=8) or B7A (CS6+ LT+ST+; mtFLS=13h; n=12), we observed that MAIT cells express higher levels of gut-homing molecules a4b7 and CCR9 7-days post-challenge. Moreover, MAIT cells also have an increase in expression of markers of activation CD38 (p=0.003) and cell proliferation Ki-67 (p=0.01) 7-days post-challenge, despite no change in overall frequency. RNA-seq revealed distinct transcriptional signatures 7-days post challenge in both challenge models. Gene set enrichment analysis (GSEA) showed that challenge with both ETEC strains elicit an upregulation of pathways involved in MAIT cell proliferation and division. Several pathways involving IL-1 secretion and the inflammasome were also upregulated after H10406 challenge. Meanwhile, B7A challenge upregulated innate-like pathways such as Natural Killer Cell Activation. These data suggest that MAIT cells are responding during ETEC challenge with upregulation markers of gut homing, activation and proliferation, but undergo differential means of activation after CHIMs with H10407 compared to the more fact-acting B7A ETEC strain.

Background In high-income countries, inflammation has been associated with increased morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals despite treatment with antiretroviral therapy (ART). However, these findings may not be generalizable to low-income settings. Methods In this cross-sectional study, multivariable linear regression was used to compare 28 inflammatory biomarker levels in HIV-infected and -uninfected participants. Correlations between biomarkers and Veterans Aging Cohort Study (VACS) index, Fibrosis-4 (FIB-4) score, and Framingham risk score were assessed. Results Plasma samples from 304 Kenyans were analyzed. Compared to HIV-uninfected controls, virologically suppressed HIV-infected participants had higher levels of CCL5, CXCL10, fatty acid binding protein (FABP) 2, fas ligand (FASLG), matrix metalloproteinase (MMP) 1, MMP7, soluble CD14 (sCD14), and soluble CD163 (sCD163) and lower MMP9 (P < .01). CD4+/HLA-DR+CD38+ (ρ = 0.32; P < .001), sCD14 (ρ = 0.25; P = .004), and sCD163 (ρ = 0.24; P = .006) were correlated with the VACS index. FABP2 was positively correlated (ρ = 0.29; P = .002), whereas MMP1 (ρ = -.32; P < .001) and MMP2 (ρ = -0.28; P = .002) were inversely correlated with the FIB-4 score. Conclusions Differences in biomarker levels exist between well-controlled HIV-infected participants on ART and uninfected controls. Some biomarkers are correlated to scoring indices predictive of morbidity and mortality. These biomarkers could serve as prognostic indicators and inform therapeutic development.

Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge. Using our method, we discover “accelerating protrusion”, which is driven by the temporally ordered coordination of Arp2/3 and VASP activities. We validate our finding by pharmacological perturbations and further identify the fine regulation of Arp2/3 and VASP recruitment associated with accelerating protrusion. Our study suggests HACKS can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation and reveal how actin regulator dynamics are changed by the perturbation., Cell protrusion dynamics are heterogeneous at the subcellular level, but current analyses operate at the cellular or ensemble level. Here the authors develop a computational framework to quantify subcellular protrusion phenotypes and reveal the underlying actin regulator dynamics at the leading edge.

We present a practical cryptanalysis of WalnutDSA, a digital signature algorithm trademarked by SecureRF. WalnutDSA uses techniques from permutation groups, matrix groups and braid groups, and is designed to provide post-quantum security in lightweight IoT device contexts. The attack given in this paper bypasses the E-Multiplication\(^{\text {TM}}\) and cloaked conjugacy search problems at the heart of the algorithm and forges signatures for arbitrary messages in approximately two minutes. We also discuss potential countermeasures to the attack.

Recently, as the drones have become smaller and smarter, they are emerging as new threats to the military and the public. To prevent the threats, the development of the radar to detect the small drones is needed. The frequency modulated continuous wave (FMCW) radar is one of the radar types for the drone detection. The heterodyne architecture for the FMCW radar is often applied to resolve the dc offset problem. However, the leakage from a transmitter into a receiver, the notorious problem of the FMCW radar, is still a challenging problem. Especially, the phase noise of the leakage increases the noise floor and deteriorates the signal to noise ratio. In order to mitigate this problem, in this paper, the stationary point concentration technique is proposed. Without additional hardware, the proposed technique can be implemented through frequency planning and digital signal processing. The results show that the proposed technique significantly lowers the noise floor over the desired range domain., Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible. arXiv admin note: text overlap with arXiv:1807.06324

The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF), a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF) prolyl hydroxylase-2 (PHD-2) was tested by an in vitro von Hippel–Lindau protein (VHL) binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM) assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α), and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1.

It is well known that the cost of executing the sequential portion of a program will limit and sometimes even eclipse the gains brought by processing in parallel the rest of the program. This means that serious consideration should be brought to bear on accelerating the execution of this unavoidable sequential part. Such acceleration can be done by boosting the operating frequency in a symmetric multicore processor. In this paper, we derive a performance and power model to describe the implications of this approach. From our model, we show that the ratio of performance over energy during the sequential part improves with an increase in the number of cores. In addition, we demonstrate how to determine with the proposed model the optimal frequency boosting ratio which maximizes energy efficiency.