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For breast cancer treatment, hormone therapy is effective for hormone receptor-positive breast cancer but not for TNBC (triple-negative breast cancer). Thus, many researchers have attempted to identify more effective therapeutic candidates for all subtypes of breast cancer. In this study, we established an RNA-seq analytical pipeline to analyze the subtype-specific functions of EHMT2 in the MB231 and MCF7 cell lines. After EHMT2 knockdown, we identified subtype-specific DEGs (differentially expressed genes) and overlapping DEGs. Through GO (Gene Ontology) analysis, GSEA (gene set enrichment analysis), and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis using the DEGs, we identified the subtype-specific functions of EHMT2 in the MB231 and MCF7 cell lines. Therefore, herein, we suggest that EHMT2 is an attractive therapeutic target for the treatment of all types of breast cancer. • EHMT2 knockdown suppressed cell proliferation and migration/invasion in MB231 and MCF7. • In RNA-seq analysis, EHMT2 have cell type specific functions in MB231 and MCF7. • EHMT2 is an attractive therapeutic target for treating all types of breast cancer. [ABSTRACT FROM AUTHOR]

This paper investigates the crash-rate distribution of the freeway weaving segments with a buffer-separated high-occupancy-vehicle lane. For this purpose, crash, traffic and geometry data were extracted from various sources. These extracted data were either spatially or spatiotemporally matched with one another, and used for both descriptive and model-based analyses. The descriptive analysis revealed that crash-rate distributions of the weaving segments depend not only on the class of the subject highway but also on the presence of an access point. This finding was statistically confirmed by crash frequency models. Notably, both descriptive and model-based analyses showed that weaving segments with an access point tend to show lower crash-rates than the counterparts without one. One might attribute this counterintuitive phenomenon to a certain underlying tendency by which traffic engineers or planners generally follow in selecting locations of an access point along the freeway. Further research is required to resolve such a conjecture. [ABSTRACT FROM AUTHOR]

Percolated networks of silver nanowires (AgNWs) have attracted intensive attention because of their remarkable mechanical stability, along with their excellent optical and electrical performance for the fabrication of flexible transparent electrodes. Most prior research has mainly focused on fabricating transparent electrodes that can be used in optoelectronic devices such as touch sensors, light emitting diodes, and photovoltaics. However, fabrication of transparent and flexible transmission lines designed to conduct alternating current of high frequency has not been reported so far. Herein, we developed highly transparent, mechanically stable transmission line by employing inverted layer processing (ILP) in order to embed the AgNWs just below the surface of a free-standing transparent polymer. For this, we synthesized polyvinyl butyral (PVB), which can be prepared from polyvinyl alcohol by reaction with butyraldehyde, for AgNW support. AgNWs deposited on a preliminary substrate (glass) were plasmonically sintered to significantly enhance their conductivity, and then transferred to the surface of the cured PVB film by the ILP. Measurements and simulation of specially designed coplanar waveguide circuits comprising AgNWs and PVB revealed that the fabricated electrode can simultaneously provide impressive transmission performance as well as excellent mechanical flexibility and transparency. An interesting finding was that the transmission characteristics and mechanical stability are in a trade-off relationship, which needs to be carefully considered in the design and selection of materials for the flexible transmission lines. [ABSTRACT FROM AUTHOR]

Abstract Various modes of epigenetic regulation of breast cancer proliferation and metastasis have been investigated, but epigenetic mechanisms involved in breast cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers (E-cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells. Therefore, our findings demonstrate functions of EHMT2 in breast cancer metastasis and suggest that targeting EHMT2 may be an effective therapeutic strategy for preventing breast cancer metastasis. Highlights • EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues. • Knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers. • EHMT2 regulated EMT markers via up-regulation of MSK1-SNAIL1. [ABSTRACT FROM AUTHOR]

This paper proposes novel mixed-mode S-parameters, which are dubbed as “extended mixed-mode S-parameters.” The extended mixed-mode S-parameters were applied to three-conductor transmission lines, resulting in the independent differential and common modes using the current division factor of three-conductor transmission lines. By contrast to the conventional mixed-mode S -parameters, there are no cross-mode S-parameters in the extended mixed-mode S -parameters, even in the asymmetrical conductor transmission lines. In addition, two new mode conversion matrices, which contain the current division factor, are also proposed to convert the extended mixed-mode S -parameters to the standard S-parameters. The validity of the proposed extended mixed-mode S -parameters and the mode conversion method were confirmed by comparing the S-parameters from the theory, EM-simulation, and experiment as well. [ABSTRACT FROM PUBLISHER]

This paper proposes electrical and mechanical diagnostic methods to estimate the aging effects of 14 American wire gage (AWG) 600 V rated shielded twisted pair (STP) cables used in nuclear power plant. The cables were accelerated to be degraded in a dry oven using Arrhenius's equation, and the properties of healthy and degraded cables were estimated electrically and mechanically as well. S-parameters were measured using a vector network analyzer (VNA) and were used to assess the aging effects of the degraded cable. An effective modulus was also used as an aging indicator of the mechanical properties. An indenter was designed and fabricated to measure the effective modulus of aged cables. Both methods' results were compared and found to be effective for diagnosing the deterioration of the aging cables. Therefore, the proposed methods could be very useful for maintaining power cables in nuclear power plants. [ABSTRACT FROM PUBLISHER]

As the age of Internet of Things (IoT) has come, national-level cyber security measures should be prepared and concrete implementation plans should be established, so that critical infrastructure can be operated and maintained safely, protected from cyber attacks. In addition, IoT services for such infrastructure should be capable of closely obtaining and processing information in environments experienced by users. To provide reliable IoT services for critical infrastructure utilizing IoT devices, based on an understanding of the vulnerabilities of IoT technology and cutting-edge cyber threats, this paper proposes methods for predicting errors that may occur in physical situations, where things are connected to each other and analyzing and modeling the errors as a functional requirement. In addition to technical measures, security guidelines are presented for individual fields, such as policy, organization, manpower, budget, industry, R&D, and education. [ABSTRACT FROM AUTHOR]

This paper proposes a novel method that analyzes voltage transfer characteristics from the primary to the secondary side of an insulation transformer. Raw data of transfer characteristics were obtained from the S -parameter measurement using vector network analyzer. To characterize transfer characteristics of an insulation transformer, the proposed method uses ABCD parameters, which are transformed from the measured S-parameters. This method enables us to predict the transferred pulse voltage waveforms in the secondary side as well as to predict the frequency-dependent gain of the insulation transformer. It is confirmed that the predicted voltage waveforms and gains in the secondary side coincide to the measured voltage waveforms quite accurately, which shows the validness of the proposed method. [ABSTRACT FROM AUTHOR]

Spatiotemporal analyses of freeway sites in Part I have shown that special-lane access points are prone to become bottlenecks. These can degrade traffic flows, sometimes in all lanes. Part II explores select impacts of re-designing the means of entering and exiting a special lane, and of altering the policy governing its use. Parametric tests were conducted using a computer simulation model that was calibrated to one of the sites studied in Part I; one with a buffer-separated carpool lane. Though less reliable than what might have been observed via experiments in real settings, the simulated findings seem to offer useful insights nonetheless. The findings indicate that traffic conditions would improve at the site by elongating the carpool lane’s buffer opening beyond its present length of 400 m. Yet, only modest improvements were predicted, even when the opening was elongated to 1000 m or more. Greater benefits were predicted from disentangling the movements made into and out of the carpool lane. This was achieved by placing first a buffer opening to serve only ingress, followed by another immediately downstream to serve egress. The benefits of this treatment were again limited, even when each tandem opening was elongated to a length of 700 m. Fully removing the buffer that physically separates the carpool lane from the regular ones was predicted to bring the greatest improvements to traffic. Also examined was pending legislation that would leave the carpool-lane buffer in place, while limiting the times of day when the lane is reserved for special use. Simulations predict that this legislation would degrade travel conditions below those that presently occur at the site. The extent of this predicted degradation varied, depending upon the time of day when the lane-use restriction went into effect. [ABSTRACT FROM AUTHOR]

Most special-use freeway lanes in the US, whether reserved for carpools, toll-paying commuters or both, are physically separated from the adjacent regular-use lanes by some form of barrier. Vehicle movements in and out of a special lane of this type are permitted only at select access points along the route. The barrier at each select point might open for a distance of 400 m or so. Limiting access in this way is said to reduce the “turbulence” that might otherwise occur were the special lane not to have a barrier, such that vehicles could instead enter or exit that lane anywhere along its length. Yet, real freeway traffic studied in spatiotemporal fashion shows that access points are prone to become bottlenecks. The problem occurs when traffic in the regular lanes becomes dense, as commonly happens during a rush. Drivers then seek refuge in the special lane in greater numbers. Since the vehicular maneuvers through the access point are focused within a limited physical space, they can become disruptive and further degrade traffic. Degradation can occur both in the special lane and in the adjacent regular ones. The damage can be worse than when there is no barrier to limit special-lane ingress and egress. The problem is shown to be reproducible across sites and across days at each site. Policy implications are discussed. Select designs and policies to address the problem are thereafter explored in Part II of the paper using traffic simulation. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) can be categorized by particle size (PM10, PM2.5 and PM1.0), which is an important factor affecting the biological response. Exposure to PM in the air (dust, smoke, dirt and biological contaminants) is clearly associated with lung disease (lung cancer, pneumonia and asthma). Although PM primarily affects lung epithelial cells, the specific response of related cell types to PM remains to be elucidated. The present study performed Gene Ontology (GO) analysis programs (Clustering GO and Database for Annotation, Visualization and Integrated Discovery) on differentially expressed genes in lung epithelial cells (WI-38 VA-13) and fibroblasts (WI-38) following treatment with PM10 and evaluated the cell-specific biological responses related to cell proliferation, apoptosis, adhesion and extracellular matrix production. The results suggested that short- or long-term exposure to PM may affect cell condition and may consequently be related to several human diseases, including lung cancer and cardiopulmonary disease. [ABSTRACT FROM AUTHOR]

Abstract: A library of approximately 40 N 1-acylated (aza)indole alkanoic esters and acids was prepared employing a microwave-assisted approach. The optimized synthetic route allows for parallel synthesis, variation of the indole substitution pattern, and high overall yield. Additionally, the procedure has been scaled up to yield multi-gram amounts of preferred indole compounds, e.g.: 2′-des-methyl indomethacin 2. The reported compounds were designed as biomedical tools for primary and secondary in vitro and in vivo studies at relevant molecular targets. [Copyright &y& Elsevier]

Abstract: A reason is unveiled for the time-varying pattern in discharge flow that is commonly observed at freeway bottlenecks. We hypothesize that four known effects in freeway traffic can interact upstream of a bottleneck in ways that trigger periodic bursts in its discharge flow. Repeated observations of a 3-km freeway stretch support the hypothesis. Controlled experiments show that the capacity-increasing mechanism can be favorably modulated by metering the site’s on-ramps in an unconventional manner. The unconventional strategy repeatedly produced higher average discharge flows and shorter on-ramp queues than did a more traditional metering policy. [Copyright &y& Elsevier]

Abstract: In South Korea, enclosed arcades have been applied to traditional markets in order to improve the physical environment of the markets. However, in some enclosed-arcade markets, occupants suffer from thermal discomfort during summer due to solar radiation overheating the indoor space. This discomfort level varies according to the market structure and arcade form. This paper presents the results of thermal surveys and temperature/humidity measurements carried out on four enclosed-arcade markets, each having a different market structure and arcade form. The paper then presents analyses of the thermal effect of the market structure and arcade form on the indoor climate. During the summers of 2003, 2004 and 2006, thermal surveys were conducted which polled responses from 156 market occupants while air temperatures and humidity levels were measured simultaneously. Numerical simulations were performed in order to evaluate eighteen different design approaches in relation to the enclosed-arcade market. The results from the temperature/humidity measurements revealed that the indoor temperature was affected by roof transmittance. In particular, in one of the four markets, where the roof transmittance was 0.7, the difference between indoor and outdoor temperatures was recorded as +4.3°C. The occupants complained of the thermal discomfort and that much of their goods had become spoiled and discolored by solar radiation. To solve this problem, the arcade roof was eventually covered with an opaque plastic material. The results from the numerical analyses using computer simulations revealed that the transmittance of the roof material was the primary design element that thermally affected the indoor climate, followed by the ventilation opening, the roof height, and the roof type. However, the effect of the ventilation opening on the indoor climate increased as the roof transmittance increased, which created a greater temperature difference between the indoor and outdoor climates on sunny summer days. [Copyright &y& Elsevier]

Abstract: General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization. [Copyright &y& Elsevier]

Abstract: An architect applies glazing to a building envelope to express an expansiveness and hi-tech quality through transparency. However, in small over-glazed buildings, the glazed envelopes often lead to an inadequate comfort level in summer, when much cooling energy is needed to improve the comfort level and occupants are forced to avoid the use of glazed envelopes. This paper presents the results of comfort survey and measurements on the indoor environment of an architecturally significant small glazed-envelope building that has received many awards for its architectural design quality, and analyzes design approaches to improve the comfort level of its occupants. During the late summer of 2002, the comfort survey was conducted, polling responses from 57 office workers, while simultaneously measuring air/surface temperatures and daylight factors. Numerical simulations were performed to investigate 13 design approaches for the improvement of the comfort level. From the temperature/daylight factor measurements, the indoor air temperature did not maintain the set-point temperature of 24.0°C even with the operation of the air-conditioning system. When using the roller shades, the intensities of illumination and luminance on each measured desk surface were unevenly distributed from 650 Lux and 51cd/m2 to 6291 Lux and 310cd/m2. From the survey, office workers suffered thermal discomfort and uncomfortable glare from high or non-uniform brightness distributions in the working areas. From the numerical analyses using computer simulations, the double-skin envelopes with the sufficient intermediate space and shading devices were suggested to improve the comfort level. [Copyright &y& Elsevier]

[Display omitted] Lactate dehydrogenase (LDH) is a critical enzyme in the glycolytic metabolism pathway that is used by many tumor cells. Inhibitors of LDH may be expected to inhibit the metabolic processes in cancer cells and thus selectively delay or inhibit growth in transformed versus normal cells. We have previously disclosed a pyrazole-based series of potent LDH inhibitors with long residence times on the enzyme. Here, we report the elaboration of a new subseries of LDH inhibitors based on those leads. These new compounds potently inhibit both LDHA and LDHB enzymes, and inhibit lactate production in cancer cell lines. [ABSTRACT FROM AUTHOR]

Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions. The studies described here characterize a G6PC2 inhibitor, designated VU0945627, previously identified as Compound 3. We show that VU0945627 preferentially inhibits human G6PC2 versus human G6PC1 but activates human G6PC3. VU0945627 is a mixed G6PC2 inhibitor, increasing the Km but reducing the Vmax for G6P hydrolysis. PyRx virtual docking to an AlphaFold2-derived G6PC2 structural model suggests VU0945627 binds two sites in human G6PC2. Mutation of residues in these sites reduces the inhibitory effect of VU0945627. VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2. Mutagenesis studies suggest this lack of inhibition of mouse G6PC2 is due, in part, to a change in residue 318 from histidine in human G6PC2 to proline in mouse G6PC2. Surprisingly, VU0945627 still inhibited glucose cycling in the mouse islet-derived βTC-3 cell line. Studies using intact mouse liver microsomes and PyRx docking suggest that this observation can be explained by an ability of VU0945627 to also inhibit the G6P transporter SLC37A4. These data will inform future computational modeling studies designed to identify G6PC isoform-specific inhibitors. • GWAS, mouse and molecular data show that G6PC2 regulates fasting blood glucose (FBG) levels. • Elevated FBG levels are associated with increased risk for type 2 diabetes and various cancers. • We characterized the specificity of a previously described G6PC2 inhibitor, called Compound 3. • Compound 3 was shown to inhibit both G6PC1 and G6PC2 but also block G6P transport. • The data will help direct the future development of G6PC2-specific inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: This Letter describes a new multi-gram synthetic protocol for the preparation of the classic tosylate labeling precursor for the D2/3 PET agent [18F]fallypride. In the course of our studies, we also discovered two novel labeling precusors, the previously undescribed mesylate and chloro congeners of fallypride. [Copyright &y& Elsevier]

The optically active lactone 1 can be transformed to a chiral building block or intermediate for constructing carbon skeletons containing either a tertiary or quaternary stereogenic center by taking advantage of the steric bulk as well as the reactivity of a trimethylsilyl group at the β-position of 1. [Copyright &y& Elsevier]

This paper proposes a novel way for the estimation of the system level electrostatic discharge (ESD) coupling using the frequency-domain measurements. $ABCD$ parameters are calculated from the measured (simulated) $S$ -parameters of the equipment under test (EUT). The transfer function of the system level ESD coupling is derived from the $ABCD$-parameters. The derived transfer function estimates the induced coupling to the EUT quite well for the input ESD stressing. For the ESD source modeling, a novel simple and efficient circuit model of ESD generator is also presented. A good agreement is obtained between the measured and simulated results based on derived coupling transfer impedance function. The proposed method permits the efficient ESD coupling analysis without the need of additional electromagnetic modeling of EUT and ESD generator for various ESD input voltage levels. [ABSTRACT FROM PUBLISHER]

The indole precursors for the acylation reaction are synthesized by esterification of commercially available indole substrates or by Fischer indole synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The hetero-structural design of Ni/NiO on silica exhibits high activity for hydrogenation. • High solubility of in-situ generated H 2 benefits to its excellent interaction with catalyst. • The activity of SiO 2 @Ni/NiO was preserved well after the reuse examination. • The wide application scope was certified among various substrates. • SiO 2 @Ni/NiO shows comparable hydrogenation performance to commercial Ru/C. Selective hydrogenation is of growing interest in biomass upgrading to be performed over non-precious metal-based catalyst in aqueous phase. Herein, a nickel/nickel oxide hetero-structural catalyst to reducing sugars hydrogenation is designed based on the tailored interfacial synergy and structural composition. Such synergistic silica @ nickel/nickel oxide (SiO 2 @Ni/NiO) with core–shell structure features in i) interconnected tubes on the shell offering spatial restriction to hydrogen attraction and reactant diffusion, ii) hetero-interfaced Ni/NiO shell balancing the H 2 and glucose adsorption chemically, iii) the core shell catalyst providing nano-reactor for reactant enrichment, furthering improving the utilization of nickel active sites. Furthermore, the high solubility of in-situ generated H 2 driven by Mg in this aqueous phase hydrogenation system greatly assist the interaction among the reactants. The SiO 2 @Ni/NiO catalyst exhibits high activity in glucose hydrogenation, under which the conversion rate and sorbitol selectivity can achieve 99 % and 90 % under mild condition of 393 K for 3 h, respectively. It also shows remarkable reuse ability and wide application scope to sugars hydrogenation in this in-situ hydrogen generation process. This proposal gains insights to cooperative catalyst design on chemical composition and nanostructure for advancing biomass-based sugars hydrogenation process. [ABSTRACT FROM AUTHOR]

This study experimentally and numerically investigated the endurance life and mechanical behavior of the ball grid array (BGA) packages according to the presence of underfill and the properties of underfill materials. Using non-underfill, medium T g underfill (120 °C) and high T g underfill (165 °C), we thoroughly investigated which underfill determines the reliability of BGA package structures. The presence or absence of the underfill fundamentally determines the reliability of the BGA package. • Reliability of BGA package/board determined by the properties of the underfill • Properties of underfill affectting the location of damage in solder joints • Providing the guidelines on underfill properties in BGA package for EV systems [ABSTRACT FROM AUTHOR]

Bacillithiol (BSH) has been prepared on the gram scale from the inexpensive starting material, d-glucosamine hydrochloride, in 11 steps and 8–9% overall yield. The BSH was used to survey the substrate and metal-ion selectivity of FosB enzymes from four Gram-positive microorganisms associated with the deactivation of the antibiotic fosfomycin. The in vitroresults indicate that the preferred thiol substrate and metal ion for the FosB from Staphylococcus aureusare BSH and Ni(II), respectively. However, the metal-ion selectivity is less distinct with FosB from Bacillus subtilis, Bacillus anthracis, or Bacillus cereus. [ABSTRACT FROM AUTHOR]

• Chemical synthesis of prostaglandin E2 metabolite "tetranor PGE1". • Heck coupling with acrolein diethyl acetal leads to an ester. • Cuprate conjugate addition to a 2-substited-5-alkoxycylopentenone. • Deuterium labeling affords a standard for a prostaglandin urinary metabolite. Prostaglandin E 2 is produced in response to inflammation, often associated with human disease. As prostaglandins are rapidly metabolized, quantification of end urinary metabolites depend on chemical synthesis of isotopically labeled standards to support metabolite quantification. A concise synthesis of tetranor-PGE 1 is described including a late stage incorporation of an isotopically labeled side-chain. [ABSTRACT FROM AUTHOR]

Hydrophilicity of original carbon materials is a dominant factor on plasma sulfonation process and catalytic performance of cellulose conversion to glucose. • Hydrophilicity of carbon support is a dominant factor on plasma sulfonation process. • The SO 3 group density of hydrophilic CB was 2.1 mmol g−1 after sulfonation. • The SO 3 group density of hydrophobic CSCNT was 0.2 mmol g−1 after sulfonation. • Cellulose conversion of hydrophilic CB was 8 times higher than hydrophobic CSCNT. • The catalytic performance of plasma-sulfonated catalysts remained over 97% after recycling. The plasma sulfonation process has shown promising results on modifying carbon materials to solid acid catalysts for cellulose conversion under dilute acid solution. However, surface hydrophilic/hydrophobic properties have a great impact on interfacial interactions between a material and aqueous reaction media. In order to explore the effects of hydrophilic/hydrophobic properties during the plasma sulfonation process, we conducted sulfonation under a 1 M sulfuric acid solution on two different carbon materials: hydrophilic carbon black (CB) and hydrophobic cup-stacked carbon nanotube (CSCNT). The total acidic and sulfonate group densities were 4.4 and 2.1 mmol g−1, and 1.5 and 0.2 mmol g−1, in plasma-sulfonated CB and CSCNT, respectively. The degree of sulfonation was strongly related to the surface chemical properties of the original carbon materials. A hydrophilic surface provided better interactions between the water and carbon surface, which increased the kinetics of the sulfonation reactions. As a result, the total densities of the acidic groups on the hydrophilic CB were much higher compared to that on the hydrophobic CSCNT under similar plasma sulfonation conditions. The cellulose conversion and glucose selectivity of plasma-sulfonated CB were 40% and 80%, respectively, which was significantly greater than that of plasma-sulfonated CSCNT (cellulose conversion of 6% and glucose selectivity of 64%). Nevertheless, both catalysts exhibited over 97% of their original catalytic activities after recycling. The results indicate that the hydrophilicity of original carbon materials is a key factor in the plasma sulfonation process. [ABSTRACT FROM AUTHOR]

Deformation bands, especially shear bands were intentionally formed in supersaturated Cu-4 at.% Ti alloy by groove-rolling with 75% area reduction. Cold deformation prior to the ageing process changed the precipitation behaviour of the alloy. The deformed structure with shear bands was maintained, without showing recovery and recrystallisation, even after prolonged ageing at 450°C for more than one day. The thermally stable shear bands act as nucleation initiation sites and prevent the expansion of discontinuous cellular precipitates. The hardness reached a value of 305 Hv and an electrical conductivity of 15% IACS (IACS = International Annealed Copper Standard. 100% IACS is defined as the conductivity corresponding to a volume resistivity at 20°C of 17.241 nΩ), compared to 283 Hv and 13% IACS for conventional solid-solutioned and peak-hardened alloy. In addition, the ageing time to reach the highest hardness was shortened from 720 to 180 min at 450°C. [ABSTRACT FROM AUTHOR]

Layered MnO 2 is very attractive cathode material for zinc-ion battery (ZIB) due to its large interlayer distance, high discharge capacity, low cost, and environmental benignity. However, layered MnO 2 exhibits capacity fading. Therefore, detailed studies of the structural transformation and electrochemical mechanism of layered MnO 2 during cycling are urgently required for performance improvement. In this contribution, we have utilized in situ synchrotron, ex situ X-ray diffraction, and ex situ synchrotron X-ray absorption spectroscopy analyses in order to evaluate the structural transformation of a layered MnO 2 during Zn-ion insertion. We found that during initial cycles, the electrode was able to maintain its layered structure; however, after prolonged cycles, it completely transformed into an irreversible spinel structure. We also observed the manganese dissolution from the electrode into the electrolyte during continuous cycling. The formation of irreversible spinel phase and manganese dissolution are responsible for capacity fading. Our findings provide the understanding for further improvement of layered MnO 2 as cathode material for next generation ZIB systems. [ABSTRACT FROM AUTHOR]

The energy demand of the commercial building sector is largely for cooling and heating and will eventually result in energy and environmental crises; therefore, enhancing the performance of the cooling and heating systems used in buildings is paramount. In response to this need, focus was set on the gas engine-driven heat pump-combined system (GHPC)—consisting of a gas engine, single-stage vapour compression system, and single-effect absorption system— that saves more energy as compared to a conventional gas engine-driven heat pump. However, so far, only the performance and transient characteristics of a fabricated GHPC have been investigated. Therefore, to ascertain the characteristics of the GHPC start-up dynamics under unsteady state operations so as to achieve efficient and stable start-up operation, experiments and simulations were attempted in this study. The transient behaviour from the start-up of this combined system in cooling and heating operating modes was also scrutinized. Accordingly, it was found that simulation results agreed well with experimental data. It was concluded that there were no large delayed responses in the absorption system during start-up operation when start-up of the absorption system is considered based on the system cooling capacity response after the solution pump starts. [ABSTRACT FROM AUTHOR]

This study examines, using actual driving and simulations, transient operation characteristics and control methods for a combined system. It consists of both single-stage compression-type and single-effect absorption-type refrigerators and is driven by the shaft power and waste heat from a gas engine. Given the complicated nature of the system, determining the unsteady-state performance and control characteristics of the entire system is difficult. Hence, it must be equipped with an adequate control system to maintain acceptable system performance. Our results reveal that this system is controlled, as predicted, under unsteady-state conditions by using a novel control method. The unsteady-state simulation model is validated by comparing the driving results with the simulated results. Thus, gas-engine-driven combined air-conditioning systems possess a response time similar to absorption-type refrigerators. This indicates that the transient response of the entire system is governed by the absorption-type refrigerator, although the cooling capacity of the absorption-type refrigerator is only 13% of the entire cooling capacity. Therefore, when designing the control system of the combined system, the fact that the entire combined system is mainly governed by the absorption-type refrigerator should be considered despite its low cooling capacity. [ABSTRACT FROM AUTHOR]

Background/Objectives Lichen planus (LP) is an inflammatory skin disorder characterized by discrete, violaceous, polygonal papules. The dermoscopic features of common inflammatory dermatoses are not well studied. Although previous studies have demonstrated the typical patterns of LP, we found some atypical dermoscopic findings without Wickham striae in patients who had been diagnosed with LP by histopathologic examination. Our aim was to assess the atypical dermoscopic patterns associated with LP. Methods We analyzed the dermoscopic features of seven LP lesions with atypical dermoscopic findings from seven patients who had been clinically and histopathologically diagnosed with LP. Results Dermoscopically, five of the seven patients showed the pigmented pattern. We observed the following diverse pigment patterns: dots/globules, diffuse peppering, perifollicular, and linear. We also observed vascular and erosive patterns of variant LP. Conclusion In this study, we emphasize the role of dermoscopy for identification of the clinical status of LP and its correlation to the results of histopathologic examinations. In addition to the typical dermoscopic patterns, dermoscopic recognition of variation in the morphology of LP could aid in the diagnosis of LP prior to histopathologic evaluation. [ABSTRACT FROM AUTHOR]

An optical spacer and a processing additive (PA) offer various advantages in the enhancement of the photocurrent in a polymer solar cell, but successful incorporation of both in one device has yet to be demonstrated. Indeed, an optical spacer is considered to conflict the use of a PA in the solar cell system. Here we demonstrate a significant enhancement of the photocurrent in a polymer solar cell via successful incorporation of a solution-processable titanium sub-oxide (TiO x ) optical spacer and a PA. By using a simple, non-material-specific, and effective vacuum treatment before deposition of the TiO x optical spacer, the conflict between the optical spacer and PA was resolved and remarkable enhancement in photocurrent was attained without any loss in the fill factor and open-circuit voltage. When the TiO x optical spacer was introduced together with the 1,8-diiodooctane additive, the power-conversion efficiencies were significantly improved from 7.63% to 9.33% for the PBDTTT-EFT:PC 70 BM device and from 5.5% to 6.46% for the P(BDT-TDPPDT-TPD)/PC 70 BM device, where PBDTTT-EFT stands for poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2- b ;4,5- b ′]dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4- b ]thiophene-)-2-carboxylate-2-6-diyl)], PC 70 BM stands for [6,6]-phenyl-C 71 -butyric acid methyl, and P(BDT-TDPPDT-TPD) stands for poly[benzodithiophene-4,6- bis (thiophen-2-yl)-2,5-dioctylpyrrolo[3,4-c]pyrrole-1,3(2H,5H)-dione-5-octylthieno[3,4-c]pyrrole-4,6-dione]. [ABSTRACT FROM AUTHOR]

Acinetobacter nosocomialisis an important nosocomial pathogen that causes a variety of human infections. However, the specific virulence factors of this microorganism have not yet been determined. We investigated the role of outer membrane protein A (OmpA) in the pathogenesis ofA. nosocomialis. A ΔompAmutant of theA. nosocomialisATCC 17903Tstrain was constructed using markerless gene deletion. The ΔompAmutant displayed reduced biofilm formation in polystyrene tubes and reduced adherence to A549 cells in comparison to the wild-type strain. These virulence traits of the ΔompAmutant strain were restored when the ompA gene was complemented. Cytotoxicity was not significantly different between the wild-type strain and the ΔompAmutant when A549 cells were infected with bacteria or treated with outer membrane vesicles (OMVs). However, OMVs from the wild-type strain induced cytotoxicity in HEp-2 cells, whereas OMVs from the ΔompAmutant did not induce cytotoxicity. Proteomic analysis of OMVs revealed that OmpA influenced the distribution of envelope and periplasmic proteins. Overall, this study is the first report that links OmpA toA. nosocomialispathogenesis, and highlights OmpA as a putative target to develop anti-virulence agents or vaccines againstA. nosocomialisinfection. [ABSTRACT FROM AUTHOR]

The influence of precipitation morphology, including continuous precipitation (CP) and discontinuous precipitation (DP), on the mechanical behaviour of Cu–Ni–Si alloys was studied. The Cu–6Ni–1.5Si (in wt%) alloy was solution heat treated at 980 °C for 2 h and aged at 500 °C for 0.5 and 3 h to produce CP and DP structures. The DP specimen showed an abnormal increase in tensile ductility with increasing strain rate, unlike the CP counterpart. The impact toughness of the DP specimen was 1.6 times greater than that of CP specimen. The fracture mode in DP specimen was mostly dimpled rupture, while the mixed mode of cleavage fracture and dimpled rupture was noted on the CP specimen. [ABSTRACT FROM PUBLISHER]

The study and development of azole-based CYP51 inhibitors is an active area of research across disciplines of biochemistry, pharmacology and infectious disease. Support of in vitro and in vivo studies require the development of robust asymmetric routes to single enantiomer products of this class of compounds. Herein, we describe a scalable and enantioselective synthesis to VNI and VFV, the two potent inhibitors of protozoan sterol 14α-demethylase (CYP51) that are currently under consideration for clinical trials for Chagas disease. A key transformation is the Jacobsen Hydrolytic Kinetic Resolution (HKR) reaction. The utility of the synthetic route is illustrated by the preparation of >25 g quantities of single enantiomers of VNI and VFV. [ABSTRACT FROM AUTHOR]

This paper describes the results of the application of laser direct imaging (LDI) lithography for dimensional tolerance improvement through surface treatment of cutting edge in the flexible fine dies (FFD). Laser direct imaging lithography was successfully performed on AISI W1-8 substrates by a specifically designed laser system using UV 355 nm light source. The characteristics of patterned line width according to conditions such as scan speed and multi pass were investigated by optical microscope. The average line width of LDIed patterns was observed to be about 1 mm. The experimental results show that the line width of patterned samples was reduced with increasing scan speed and decreasing repetition number (R/N) of scanning. This conclusion proves the feasibility in the selectively application for manufacturing flexible fine die. [ABSTRACT FROM AUTHOR]

A Cu alloy with discontinuous precipitation (DP) presents a mechanically lower strength, but a higher conductivity compared to an alloy with continuous precipitation (CP). We controlled the partial distribution of DP in the Cu matrix of Cu-4Ni-1Si alloy by changing aging time. Successive cold-working of the alloy showed that by controlling the CP and DP fractions, considerably wide ranges of strength and electrical conductivity, from 500 to 1170 MPa, and from 23 to 50% IACS, respectively, could be achieved. After cold-working, the DP region in the alloy was heavily deformed in comparison with the CP region, showing a drastic increase in strength, with only a small decrease in conductivity. • A very wide conductivity-strength combination can be obtained after cold working by controlling DP fraction in only one alloy. • DP fraction can be changed just according to the change of the aging time. • The DP region is more deformed, and the strength is more quickly increased than CP region in alloy. [ABSTRACT FROM AUTHOR]

Abstract: The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure–activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a ‘mix-and-match’ strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification. [Copyright &y& Elsevier]

Abstract: Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC50 =537nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters. [Copyright &y& Elsevier]

Summary: We have developed a robust in vivo small-molecule screen that modulates heart size and cardiomyocyte generation in zebrafish. Three structurally related compounds (Cardionogen-1 to Cardionogen-3) identified from our screen enlarge the size of the developing heart via myocardial hyperplasia. Increased cardiomyocyte number in Cardionogen-treated embryos is due to expansion of cardiac progenitor cells. In zebrafish embryos and murine embryonic stem (ES) cells, Cardionogen treatment promotes cardiogenesis during and after gastrulation, whereas it inhibits heart formation before gastrulation. Cardionogen-induced effects can be antagonized by increasing Wnt/β-catenin signaling activity. We demonstrate that Cardionogen inhibits Wnt/β-catenin-dependent transcription in murine ES cells and zebrafish embryos. Cardionogen can rescue Wnt8-induced cardiomyocyte deficiency and heart-specific phenotypes during development. These findings demonstrate that in vivo small-molecule screens targeting heart size can reveal compounds with cardiomyogenic effects and identify underlying target pathways. [ABSTRACT FROM AUTHOR]

The inducible microsomal prostaglandin E2 synthase 1 (MPGES1) is an integral membrane protein coexpressed with and functionally coupled to cyclooxygenase 2 (COX-2) generating the pro-inflammatory molecule PGE2. The development of effective inhibitors of MPGES1 holds promise as a highly selective route for controlling inflammation. In this paper, we describe the use of backbone amide H/D exchange mass spectrometry to map the binding sites of different types of inhibitors of MPGES1. The results reveal the locations of specific inhibitor binding sites that include the GSH binding site and a hydrophobic cleft in the protein thought to accommodate the prostaglandin H2 substrate. In the absence of three-dimensional crystal structures of the enzyme-bound inhibitors, the results provide clear physical evidence that three pharmacologically active inhibitors bind in a hydrophobic cleft composed of sections of transmembrane helices Ia, IIb, IIIb, and IVb at the interface of subunits in the trimer. In principle, the H/D exchange behavior of the protein can be used as a preliminary guide for optimization of inhibitor efficacy. Finally, a comparison of the structures and H/D exchange behavior of MPGES1 and the related enzyme MGST1 in the presence of glutathione and the inhibitor glutathione sulfonate confirms the unusual observation that two proteins from the same superfamily harbor GSH binding sites in different locations. [ABSTRACT FROM AUTHOR]

Wnt/β-catenin signaling is critically involved in metazoan development, stem cell maintenance and human disease. Using Xenopus laevis egg extract to screen for compounds that both stabilize Axin and promote β-catenin turnover, we identified an FDA-approved drug, pyrvinium, as a potent inhibitor of Wnt signaling (EC50 of ∼10 nM). We show pyrvinium binds all casein kinase 1 (CK1) family members in vitro at low nanomolar concentrations and pyrvinium selectively potentiates casein kinase 1α (CK1α) kinase activity. CK1α knockdown abrogates the effects of pyrvinium on the Wnt pathway. In addition to its effects on Axin and β-catenin levels, pyrvinium promotes degradation of Pygopus, a Wnt transcriptional component. Pyrvinium treatment of colon cancer cells with mutation of the gene for adenomatous polyposis coli (APC) or β-catenin inhibits both Wnt signaling and proliferation. Our findings reveal allosteric activation of CK1α as an effective mechanism to inhibit Wnt signaling and highlight a new strategy for targeted therapeutics directed against the Wnt pathway. [ABSTRACT FROM AUTHOR]

Abstract: This letter describes the synthesis and SAR, developed through an iterative analogue library approach, of an mGluR4 positive allosteric modulator lead based on a pyrazolo[3,4-d]pyrimidine scaffold. Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described. [Copyright &y& Elsevier]

The discontinuous precipitation (DP) was known to mechanically detrimental mechanism compared to normal precipitation (continuous precipitation, CP), while the DP has the higher conductivity because of low solute content in matrix. To get the optimum balance of strength and conductivity, the bimodal-structured Cu-4Ni-1Si alloy composed of two regions with CPs and DPs was fabricated. Bimodal-structured alloy occupied by 50% of each region shows remarkable high strength and conductivity combination (1088 MPa / 38%IACS) beyond the expected values which summated in alloys with fully CP or DP. The accelerated strengthening of bimodal-structured alloy is caused by uni-directional alignment and enhanced plastic deformation of DPs in alloy after cold-working. • Bimodal structured Cu-Ni-Si alloy was composed of two regions with continuous and discontinuous precipitates. • Bimodal structured alloy had best combination of strength and conductivity compared to the alloys with fully continuous or discontinuous precipitates • The unidirectional alignment of discontinuous precipitates during cold-working drastically increased the strength of Cu-Ni-Si alloy. [ABSTRACT FROM AUTHOR]

Metal sulfide materials serve as environment-friendly, sustainable, and effective electrode materials for green-energy storage systems. However, their capacity-fading issues related to low electrical conductivity and drastic volume changes during electrochemical cycling have generally limited their application to sodium ion batteries. Here we show that with the combination of an ether-based NaPF6/diglyme electrolyte, the dandelion-shaped manganese sulfide electrode displays enhanced reversible capacity, cycle life, and rate capability. The capacity of 340 mAh g−1 is maintained over more than 1000 cycles at a current density of 5.0 A g−1. Furthermore, discharge capacities of 277 and 230 mAh g−1 at 10 and 20 A g−1 current densities, respectively, are obtained. Our work demonstrates the formation of a protective solid electrolyte interface layer along the surface of the primary seed particle that limits polysulfide dissolution and hence the preservation of the active material during reaction with sodium. Metal sulfide batteries suffer from low electrical conductivity which limits their application in sodium ion batteries. Here, the authors report a manganese sulfide anode in sodium ion batteries with capacity of 340 mAh g−1 maintained over more than 1000 cycles at a current density of 5.0 A g−1. [ABSTRACT FROM AUTHOR]