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ABSTRACTAiming to explore the meaning and value of the space of a sports club for university students in South Korea, this study employs the idea of spatial culture by Henri Lefebvre. The foundation of the cultural experience of a sports club is the cultural experience of a specific space; therefore, this paper takes the concern of spatial culture as the theoretical starting point. The research method is participant observation, and the researchers explored a sports club culture in South Korea for 4 months. The topics discussed in this study, such as, the boundaryless atmosphere within the sports club which provides the possibility for students to seek empathy; the sports club provides an obvious boundary with daily life which allows students to build another identity for resisting dissatisfaction with life; and last, it also provides the possibility of learning for students in a changing and diverse campus environment.

A 5-layer laminated metal composite composed of ultrahigh-strength maraging steel and ductile 316L stainless steel was fabricated by hot pressing in vacuum and post-heat treatment. Microstructure characterization on hierarchical structure of the composite before and after heat treatment was made by optical microscopy, scanning electron microscopy and electron back-scattered diffraction technique, respectively. Meanwhile, the difference of mechanical performance on both sides of the interface was characterized by nano-hardness testing. Uniaxial tensile test showed that superior interfacial bonding was achieved due to the micro-‘bite’ structure between the two steels without obvious defects or oxides at the interface and with coordinated deformation of the two components. Thus, a laminated metal composite consisting of two different constituents with extreme difference in strength can be well fabricated.

The phase volume fraction has an important role in the match of the strength and plasticity of dual phase steel. The different bainite contents (18–53 vol.%) in polygonal ferrite and bainite (PF + B) dual phase steel were obtained by controlling the relaxation finish temperature during the rolling process. The effect of bainite volume fraction on the tensile deformability was systematically investigated via experiments and crystal plasticity finite element model (CPFEM) simulation. The experimental results showed that the steel showed optimal strain hardenability and strength–plasticity matching when the bainite reached 35%. The 3D-CPFEM models with the same grain size and texture characters were established to clarify the influence of stress/strain distribution on PF + B dual phase steel with different bainite contents. The simulation results indicated that an appropriate increase in the bainite content (18%–35%) did not affect the interphase strain difference, but increased the stress distribution in both phases, as a result of enhancing the coordinated deformability of two phases and improving the strength–plasticity matching. When the bainite content increased to 53%, the stress/strain difference between the two phases was greatly increased, and plastic damage between the two phases was caused by the reduction of the coordinated deformability.

Because of the rapid development of power electronics, DC loads, and distributed energy resources, the advantages of DC distribution systems are increasingly prominent. This paper provides a brief description of the concepts and functional advantages of DC distribution systems, introducing the main equipment of multi-terminal DC (MTDC) distribution system, the topologies, and the typical application scenarios of each topology. The coordinated control technology of MTDC distribution system is analysed and summarized in terms of control architecture, coordinated control, damping control, and operation mode. The existing MTDC distribution demonstration projects are summarized, and recent typical projects are introduced. Finally, the issues that can be studied regarding to the innovation and application of MTDC distribution system are pointed out.

Avian influenza is a disease of poultry that causes economic losses to poultry farms. Conventional vaccine production requires chicken embryos for virus proliferation with time-consuming and also affected by egg supply during the avian influenza virus outbreak. There are several advantages of plant cells as bio-factories for vaccine production, including low cost, low risk of contamination, and even edible. In this study, we chose carrot (Daucus carota) as a bioreactor to produce hemagglutinin (HA), an avian influenza virus antigen protein. HAgene linked with heat-labile enterotoxin B subunit (LTB) gene whose product plays the role of adjuvant protein was codon optimized with codon usage bias of carrot for high-level expression. The native and codon-optimized LTB–HAwere transformed into carrots by Agrobacterium-mediated transformation. T-DNA insertion of two version constructs was confirmed by polymerase chain reaction. Integration of codon-optimized LTB–HAgene in all transgenic carrot lines was identified as a single copy by Southern blot analysis. LTB–HA protein expressed in carrot cells was determined through enzyme-linked immunoassay. Codon-optimized LTB–HAgene showed a better expression level than the native LTB–HAgene in transgenic carrots. The highest expression level of LTB–HA in codon-optimized LTB–HA-transformed carrot taproot reached up to 0.0108% of total soluble protein. This study is the first report about expression of HA antigen of H5N2 subtype AIV in a horticultural crop. Our transgenic carrots have successfully produced HA protein which shows great potential to become an edible vaccine against avian influenza virus.

Root microbiota affect the host plant's adaptation to adverse environments. The structure and function of plant root bacterial communities are affected by soil physicochemical properties and plant genotypes. Distant hybridization is a common breeding strategy to introgress the excellent genes of wild relatives into the crop genome. The effect of distant hybridization on the crop root microbiota has not been reported. In this study, the structure and function of root bacterial community of the somatic hybrid wheat introgression lines SR3 and SR4, which have been respectively reported to be tolerant to salt and saline‐alkali stress, and their parent wheat cultivar JN177 as well as common wheat cultivar Chinese Spring (CS) were analyzed using 16S rRNA high‐throughput sequencing technology. The results showed that distant hybridization altered the structure and function of wheat (Triticum aestivumL.) root bacterial community. Compared with the parent JN177, some bacterial genera related to plant growth and stress resistance showed higher abundance in SR3 and SR4. Intriguingly, compared with parent JN177, the root bacterial communities of SR3 and SR4 are more similar to that of CS. This indicated that the process of distant hybridization may alter key genes regulating wheat root microbiota. Distant somatic hybridization altered the structure of wheat root bacterial community.Bacterial genera related to stress resistance showed higher abundance in wheat introgression lines.The process of distant somatic hybridization may alter key genes regulating wheat root microbiota.Distant somatic hybridization alters the structure of wheat root bacterial microbiota.

Cyclocarya paliurus(Batal.) Iljinskaja is a special plant species grown at high elevation in southwestern China. The bark, leaves, and roots are used for many purposes including reduction of fever and enhancement of blood insulin level. However, its growth is usually limited by the fragile environment and climate variability. Previous studies attributed the environment‐relevant yield reductions to stress induced gene expression changes. The accuracy and reliability of reverse transcription quantitative polymerase chain reaction (RT‐qPCR), a commonly accepted gene expression method, depends on the choice of appropriate reference genes, which are used for gene expression normalization. However, there are no reports at present about reference genes of C. paliurusunder environmental stresses. Therefore, this study was conducted to identify reference genes for C. paliurusunder environmental stresses. In this work, we selected seven common reference genes as our candidates: ACT2, ACTF, GAPDH, TUA, TUB, UBQ4, and 18SrRNA. The stability of these seven reference genes in C. paliuruswas quantified by RT‐qPCR and evaluated by geNorm and NormFinder algorithms. The results suggest that although there were variations of the stability of the internal reference genes, two of them were usually good enough for the normalization purpose for low temperature (4 °C), high salinity (NaCl), and drought stress (polyethylene glycol [PEG] treatment). However, these genes should not be used for high‐temperature (42 °C) stress. This study provides insight for reference gene selection under experimental stresses in C. paliurus. It also sets the foundation of wide and accurate use of RT‐qPCR under environmental stresses. The optimal number of reference genes under different abiotic stresses in Cyclocaryawas determined.The average expression stability values (M) of internal reference gene were determined.GAPDHwas identified as the best reference gene in the current research.TUBis the most unstable gene via agrose gel electrophoresis and RT‐qPCR.This study summarizes the optimal reference genes in crop plants.

The plant rhizosphere bacterial community influences plant stress resistance. Stripe rust causes severe damage to wheat (Triticum aestivumL.) production. To reveal the composition and function of root bacterial communities in wheat cultivars with different stripe rust resistance, rhizosphere soil samples were collected from four wheat cultivars. High‐throughput 16S rRNA gene sequencing was used to study the rhizobacterial community structure and function in stripe rust‐resistant (Guinong 19 and Huamai 1223) and ‐susceptible (Mingxian 169 and Taichung 29) wheat cultivars. A total of 6,392 operational taxonomic units (OTUs) were detected, belonging to 29 bacterial phyla. Analysis showed the susceptible and resistant wheat cultivars had different microbial communities. Principal coordinate analysis showed that all wheat rhizosphere bacterial samples could be divided into two groups, according to different disease resistance. Linear discriminant analysis effect size analysis showed that different bacterial taxa were enriched in the rhizosphere soil between resistant and susceptible wheat cultivars. Functional analysis showed that the bacterial community in stripe rust‐resistant wheat had greater amino acid transport and metabolic functions. Our research not only provides basic knowledge of the composition of wheat‐related microbiota but also reveals the microbial taxa that could be integrated into the management strategy of wheat stripe rust.

Environmental stresses may trigger the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), thus leading to ER stress in plants. Endoplasmic reticulum stress, harmful to plant growth, can be alleviated by upregulating unfolded protein response (UPR) initiated by transcription factors. NAC062 and NAC103, as reported in previous studies, both play significant roles in upregulating UPR genes to promote cell survival under ER stress in Arabidopsis. It is still unclear, however, which one of them acts as an upstream regulator in the ER stress pathway. Results of the current study demonstrated that NAC062 acts as an upstream regulator to directly regulate the expression of NAC103to mediate ER stress in mouse‐ear cress [Arabidopsis thaliana(L.) Heynh]. The expression of NAC103is upregulated by the overexpression of NAC062D(the nuclear localization form of NAC062). Through subsequent dual‐luciferase reporter assay and yeast one‐hybrid (YIH) assay, NAC062D was found directly bound to the NAC103promoter. The results of real‐time reverse transcription polymerase chain reaction (qRT‐PCR) showed that NAC062and NAC103are both upregulated in biotic stress (jasmonic acid [JA] treatment) and abiotic stress (such as salt stress, oxidation stress, and cold stress) pathways. Studying the relationship between NAC062 and NAC103 is beneficial to understand their function in biotic and abiotic stress pathways, so as to enhance plants tolerance under environmental stresses. NAC062 acts as an upstream regulator of NAC103under endoplasmic reticulum stress.The overexpression of NAC062Dupregulated the expression of NAC103in plants.NAC062D can directly bound to the NAC103promoter.NAC062and NAC103are both upregulated in biotic stress and abiotic stress pathways in plants.

Background: The potential effects of global warming on soil fungal communities and their functions remain uncertain. To address this issue, we investigated the effects of 3-year simulated field warming on the community and function of fungi in a temperate steppe of Inner Mongolia, northern China. Methods: The diversity and structure of the fungal community were measured by high-throughput sequencing. The functionality of fungal communities was identified by comparison with the ITS reference database. Results: Our results showed that warming did not affect the diversity of fungi, but significantly increased the complexity of the fungal community, with fungal taxa more closely associating with each other. We observed that plant pathogens and arbuscular mycorrhizal fungi were the most abundant functional groups. Meanwhile, warming significantly decreased the relative abundance of animal pathogens. Conclusions: Warming significantly increased the complexity of the fungal community, with soil pH being the main factor affecting soil fungal function. Our findings emphasize that the response of the fungal community and its functional groups to warming has significant implications for ecosystem biogeochemical cycling.

Despite the growth of photoredox methods in academia, application of photoredox at scale in the pharmaceutical and fine chemical industries has been slow. In this report, a photoredox trifluoromethylation of a thiophenol was modified from the original literature report, and the mechanism was investigated to define the key scale-up parameters. The mechanistic insight was leveraged in the design and execution of two different reactor designs: an LED-based plug flow photoreactor and a laser-based continuous stirred tank photoreactor. In one of the first examples of commercial-scale photoredox chemistry, the process was scaled to provide over 500 kg of the desired intermediate and amended to fully continuous manufacturing.

Rosa sterilisS. D. Shi is an important economic tree in China that produces fruits with high nutritional and medicinal value. Many of R. sterilis' organs are covered with different types of trichomes or prickles that directly affect fruit appearance and plant management. This study used RNA sequencing technology to analyze the transcriptomes of two parts of the inflorescence branch, namely inflorescence stems with flagellated trichomes and pedicels with both flagellated and glandular trichomes. Comparative transcriptomic analysis showed that many transcription factors (TFs) are potentially involved in the formation and development of trichomes. The accumulation of RsETC1, a TF of the R3-MYB family, was significantly higher in inflorescence stems than in pedicels; quantitative reverse transcription PCR (qRT-PCR) verified that its expression was significantly higher in inflorescence stems than in pedicels during the first three development stages, indicating its inhibitory action on the initiation of glandular trichomes in R. sterilis. The mRNA level of RsETC1accumulated to significantly higher levels in trichomeless tissues than in tissues with trichromes, suggesting that this gene may inhibit the formation of trichomes in R. sterilis. Over-expression of RsETC1in Arabidopsisresulted in glabrous phenotypes, and the expression of trichome-related endogenous genes, except for TTG1, was markedly reduced. In addition, the contents of the phytohormones jasmonic acid (JA), gibberellin A3 (GA3), and cytokinins (CKs) in pedicels were significantly higher than those in inflorescence stems, and the expression patterns of the genes related to hormone biosynthesis and signal transduction presented consistent responses, suggesting that the transduction of these hormones might be crucial for trichome initiation and development. These data provide a new perspective for revealing the molecular mechanism of trichome formation in R. sterilis.

Sugarcane has a large, complex, polyploid genome that has hindered the progress of genomic research and molecular marker-assisted selection. The user-friendly SSR markers have attracted considerable attention owing to their ideal genetic attributes. However, these markers were not characterized and developed at the genome-wide scale due to the previously lacking high-quality chromosome-level assembled sugarcane genomes. In this present study, 744305 and 361638 candidate SSRs were identified from the genomes of S. officinarumand S. spontaneum, respectively. We verified the reliability of the predicted SSRs by using 1200 interspecific SSR primer pairs to detect polymorphisms among 11 representative accessions of Saccharum, including S. spontaneum, S. officinarum, S. robustum, and modern sugarcane hybrid. The results showed that 660 SSR markers displayed interspecific polymorphisms among these accessions. Furthermore, 100 SSRs were randomly selected to detect the genetic diversity for 39 representative Saccharumaccessions. A total of 320 alleles were generated using 100 polymorphic primers, with each marker ranging from two to seven alleles. The genetic diversity analysis revealed that these accessions were distributed in four main groups, including group I (14 S. spontaneumaccessions), group II (two S. officinarumaccessions), group III (18 modern sugarcane hybrid accessions), and group IV (five S. robustumaccessions). Experimental verification supported the reliability of the SSR markers based on genome-wide predictions. The development of a large number of SSR markers based on wet experiments is valuable for genetic studies, including genetic linkage maps, comparative genome analysis, genome-wide association studies, and marker-assisted selection in Saccharum.

The Calvin–Benson cycle (CBC) consists of three critical processes, including fixation of CO2by Rubisco, reduction of 3-phosphoglycerate (3PGA) to triose phosphate (triose-P) with NADPH and ATP generated by the light reactions, and regeneration of ribulose 1,5-bisphosphate (RuBP) from triose-P. The activities of photosynthesis-related proteins, mainly from the CBC, were found more significantly affected and regulated in plants challenged with high temperature stress, including Rubisco, Rubisco activase (RCA) and the enzymes involved in RuBP regeneration, such as sedoheptulose-1,7-bisphosphatase (SBPase). Over the past years, the regulatory mechanism of CBC, especially for redox-regulation, has attracted major interest, because balancing flux at the various enzymatic reactions and maintaining metabolite levels in a range are of critical importance for the optimal operation of CBC under high temperature stress, providing insights into the genetic manipulation of photosynthesis. Here, we summarize recent progress regarding the identification of various layers of regulation point to the key enzymes of CBC for acclimation to environmental temperature changes along with open questions are also discussed.

Renewable energy complementary hydrogen production can enhance the full consumption of renewable energy and reduce the abandonment of wind and solar power. The integration of renewable energy and hydrogen production equipment through existing multi-terminal DC systems can reduce new power lines construction and save investment in distribution equipment. For integrated renewable energy/hydrogen energy in an existing multi-terminal DC system, this paper investigates its potential of hydrogen production based on renewable energy, while ensuring the normal performance of the existing system being not affected. The typical structure and control strategy of the integrated renewable energy/hydrogen energy in multi-terminal DC system are firstly described. Then the state space model of the system is constructed, and the key parameters affecting the hydrogen production capacity are studied by using the eigenvalues analysis method. Finally, the corresponding system simulation model and test platform are built, and the theoretical analysis results are verified, and the potential of using multi-terminal DC system to enhance hydrogen production is quantitatively analyzed. The proposed scheme can enhance the hydrogen production potential from renewable energy, meanwhile the normal performance of the existing system is not affected.

Background. Hepatolithiasis associated with cholangiocarcinoma is not often encountered. During the past 3 years, an increased incidence of patients with hepatolithiasis associated with cholangiocarcinoma was noted. Data were needed to reliably determine the incidence of this disease. Methods. Data concerning the relationship between cholangiocarcinoma and hepatolithiasis are presented. The treatment modalities and factors that influence long-term survival are discussed. Results. The overall incidence of cholangiocarcinoma in association with hepatolithiasis was 5.0% (55 in 1105). Before 1987,65% of cholangiocarcinoma in association with hepatolithiasis was diagnosed postoperatively. After 1987, the incidence of accurate preoperative diagnosis increased (22.8%), and in most of the other instances (62.8%), the diagnosis was made at laparotomy. Surgical procedures consisted of common bile duct exploration with T-tube drainage (100%) and hepatectomy (38.2%). Mortality for patients who underwent surgery was 5.4%; they died of recurrent cholangitis. The overall median survival time of patients with cholangiocarcinoma in association with hepatolithiasis was 10.4 months; the 1-, 2-, and 4-year cumulative survival rates were 30.0%,12.7%, and 3.6%, respectively. Patients with hepatectomy or the presence of mucobilia had better survival rates (P < 0.05). Conclusions. The overall incidence of hepatolithiasis associated with cholangiocarcinoma was 5%. In most patients with cholangiocarcinoma in association with hepatolithiasis, diagnosis can be made preoperatively and at laparotomy. Patients with hepatectomy or presence of mucobilia had better survival rates. Cancer 1993; 71:2461-5.

Byline: Kun-Chun. Chiang, Chun-Hui. Lee, Chun-Nan. Yeh, Shir-Hwa. Ueng, Jun-Te. Hsu, Ta-Sen. Yeh, Yi-Yin. Jan, Tsann-Long. Hwang, Miin-Fu. Chen Background: Pancreatic adenocarcinoma (PCA) is a devastating disease. Only surgery can [...]

The subgenomic mRNA (sgRNA) promoter for coat protein(CP) was isolated from the cDNA infectious clone of Odontoglossum ringspot virusTaiwan strain (ORSV-TW), which is a positive single-stranded RNA virus of the Tobamovirusfamily. The 5′-end deletion analysis of the 290 nucleotides ORSV CPsgRNA promoter was performed to investigate the promoter activity. A series of different ORSV CPsgRNA promoter deletions were characterized by driving the expression of a fused green fluorescent protein(GFP)-β-glucuronidase(GUS) gene using Agrobacterium-mediated infiltration in Phalaenopsispetals and Nicotiana benthamianaleaves. The results of deletion analysis indicated that the region between 24 nucleotides upstream and 18 nucleotides downstream of translation start codon was sufficient for promoter activity. The activity of this minimal promoter was relatively stronger than other promoters with longer length. A minimal ORSV CPsgRNA promoter was found to accumulate high levels of GFP and GUS, suggesting that this sequence might drive the foreign protein expression in heterologous systems.

An efficient C&–P bond formation reaction was developed by virtue of the synergetic catalysis strategy by merging heterogeneous photocatalysis and nickel catalysis. This platform utilizing cadmium sulfide semiconductors as heterogeneous photocatalysts and nickel complexes as transition metal catalysts provided a variety of organophosphorus compounds from readily available aryl and vinyl halides, as well as aryl triflates, with generally a good-to-excellent reaction efficiency (31 examples, 46%-98% yields). The current protocol features mild reaction conditions, a broad substrate scope, recyclability of photocatalysts, and inexpensive catalysts, thus defining the practical and economic proprieties of the present catalyst system.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)–dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α–dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2Eintron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)–specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Hot processing behavior of an ultra-high-strength Fe–Ni–Co-based maraging steel was studied in temperature range of 900–1200 °C and strain rate range of 0.001–10 s−1. Deformation processing parameters and optimum hot working window were characterized via flow stress analysis, constitutive equation construction, hot processing map calculation and microstructure evolution, respectively. Critical strain value for dynamic recrystallization was determined through theoretical mathematical differential method: the inflection point of θ–σand − ∂θ/∂σ− σcurves. It was found that the flow stress increased with the decrease in deformation temperature and increase in the strain rate. The power dissipation maps in the strain range of 0.1–0.6 were entirely similar with the tendency of contour lines which implied that strain had no strong effect on the dissipation maps. Nevertheless, the instability maps showed obvious strain sensitivity with increasing strain, which was ascribed to the flow localization and instability. The optimized hot processing window of the experimental steel was obtained as 1100–1200 °C/0.001–1 s−1and 1000–1100 °C/0.001–0.1 s−1, with the efficiency range of 20–40%. Owing to high Mo content in the experimental steel, high dynamic activation energy, Q = 439.311 kJ mol−1, was achieved, indicating that dynamic recrystallization was difficult to occur in the hot deformation process, which was proved via microstructure analysis under different hot deformation conditions.

The hot deformation behavior and workability of a new reduced activation ferritic/martensitic steel named SIMP steel for accelerator-driven system were studied. The flow curve and its microstructure were studied at 900–1200 °C and strain rate range of 0.001–10 s−1. The results showed that the deformation behavior of the SIMP steel during hot compression could be manifested by the Zener–Hollomon parameter in an exponent-type equation. Based on the obtained constitutive equation, the calculated flow stresses were in agreement with the experimentally measured ones, and the average activity energies QDRVand QHWfor the initiation of dynamic recrystallization and the peak strain were calculated to be 476.1 kJ/mol and 462.7 kJ/mol, respectively. Furthermore, based on the processing maps and microstructure evolution, the optimum processing condition for the SIMP steel was determined to be 1050–1200 °C/0.001–0.1 s−1.

A novel visible-light photoredox-catalyzed phosphinyloxy radical addition/cyclization cascade of arylphosphinic acids or arylphosphonic acid monoesters with alkynes has been developed, which provides an efficient and practical access to various phosphaisocoumarins by using a dual catalytic system containing an acridinium photosensitizer and a cobaloxime proton-reducing catalyst [Co(dmgH)2]PyCl at ambient temperature. This method has advantages of a broad substrate scope, mild condition, as well as no sacrificial oxidant.

The process development of a new synthetic route leading to an efficient and robust synthetic process for venetoclax (1: the active pharmaceutical ingredient (API) in Venclexta) is described. The redesigned synthesis features a Buchwald-Hartwig amination to construct the core ester 23cin a convergent fashion by connecting two key building blocks (4cand 26), which is then followed by a uniquely effective saponification reaction of 23cusing anhydrous hydroxide generated in situto obtain 2. Finally, the coupling of the penultimate core acid 2with sulfonamide 3furnishes drug substance 1with consistently high quality. The challenges and solutions for the key Pd-catalyzed C–N cross-coupling will also be discussed in detail. The improved synthesis overcomes many of the initial scale-up challenges and was accomplished in 46% overall yield from 3,3-dimethyldicyclohexanone (6), more than doubling the overall yield of the first generation route. The new process was successfully implemented for producing large quantities of 1with >99% area purity.

The glycine transporter 1 (GlyT1) has emerged as a key novel target for the treatment of schizophrenia. Herein, we report the synthesis and biological evaluation of aminotetralines and aminochromanes as novel classes of competitive GlyT1 inhibitors. Starting from a high-throughput screening hit, structure–activity relationship studies led first to the discovery of aminotetralines displaying high GlyT1 potency and selectivity, with favorable pharmacokinetic properties. Systematic investigations of various parameters (e.g., topological polar surface area, number of hydrogen bond donors) guided by ex vivo target occupancy evaluation resulted in lead compounds possessing favorable brain penetration properties as for (7S,8R)-27a. Further optimization revealed compounds with reduced efflux liabilities as for aminochromane 51b. In an in vivo efficacy model (7S,8R)-27a, dose-dependently reversed L-687,414 induced hyperlocomotion in mice with an ED50of 0.8 mg/kg. All these results suggest (7S,8R)-27aand 51bas new GlyT1 inhibitors worthy of further profiling.

Corrosion resistance behavior of Co-containing maraging stainless steels was investigated. Neutral salt spray and polarization test showed that maraging stainless steel with high Co content showed poor corrosion behavior. Microstructure observation proved that segregation of Cr in the matrix deteriorated its corrosion resistance. The surface morphology of the aged maraging stainless steel with high Co content indicated that during passivation process, the newly formed passive film with sinusoidal distribution readily destroyed by the corrosive medium, hence, causing poor corrosion resistance. Moreover, through first-principles calculation it was proved that Co increased Fe–Fe ferromagnetic interaction which facilitated the formation Cr-rich clusters.

Uncertain renewable power generation and on-site demand complicate battery operation and affect profitability. In this paper, a novel battery scheduling model (including the single- and multi-interval patterns) is proposed for maximizing arbitrage benefits while meeting the peak shaving requirements. The proposed model features accurate expectations and is essentially a stochastic optimization accounting for uncertainty. The convexity of the proposed model is strictly proved, which ensures that the global optimal solution is obtainable and computationally attractive. Based on the first-order optimality condition, we further derive the analytical form of the optimal solution, which explicitly demonstrates the impact of uncertainty on the optimal schedule of battery storage. Both the convexity and solution stability of the proposed model are verified through case studies involving various time periods and multiple algorithms for convex optimization. In addition, the change in the trade-off price threshold caused by uncertainty is also illustrated in simulations.

The rapid coarsening of the M23C6carbides has been held responsible for the creep fracture in 9–12Cr martensitic heat resistant steels. A commercial P92 steel was subjected to thermal aging at a high temperature of 800 °C to investigate the ripening behavior of the M23C6carbides. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to characterize the microstructure evolution, especially the ripening process of the M23C6carbides. The new concept of the effective mean size, dependent on the critical radius, was introduced to correct the measured mean size and then the Ostwald theory was applied to describe the ripening behavior of the M23C6carbides. The ripening of the M23C6carbides was revealed to be grain boundary diffusion controlled.

The segregation of Cu and Ni in a 17-4PH stainless steel piston rod has been confirmed to be responsible for the cracking after heat treatment. Further investigation showed that the segregation zone was composed of three layers, namely the fine grain martensitic layer, the coarse grain martensitic layer and the coarse grain austenitic layer from the matrix to the crack surface. Three button ingots with the same chemical compositions as those three layers have been prepared to evaluate the grain size distribution, microstructure and mechanical properties. The effects of Cu and Ni segregation on the microstructures of those three layers have been explored by thermodynamic calculation. Based on the microstructure and mechanical properties results, an intensive understanding of the cracking in the segregation zone was therefore reached.

In the present study, Cu-modified pipeline steels were fabricated to mitigate MIC by the antimicrobial ability of Cu element. The microstructure, mechanical properties and the antimircobial performance of the Cu-modified steel were systematically investigated. The Cu-modified steels showed good antimicrobial performance with remarkable strength enhancement by nanoscale Cu-rich precipitates and good impact toughness without changing the original base microstructures after the optimal aging treatment of 500 °C/1 h.

Peripheral cholangiocarcinoma (PCC) is a cancerous tumor derived from the cells lining the small bile ducts of the liver. Cholangiocarcinoma is associated with the formation of stones in the liver ducts. Treatment includes the surgical removal, hepatic resection, of the diseased sections of the liver. Over a ten year period, hepatic resection was performed on nine men and 11 women with PCC. A history of liver stones, hepatolithiasis, was present in 80 percent of the patients. Additional surgery was performed because of recurrent inflammation due to liver stones or other space-occupying tumors on liver scans. Twelve patients had surgery for liver stones when PCC was diagnosed. The surgical mortality rate was low and few complications developed in patients with liver stones. Infection was the most common complication. Patients with PCC survived an average of 20.5 months. Four patients survived three years and one more than five years after surgery. There seems to be an association between liver stones and PCC. It is suggested that the chronic inflammation and infection associated with liver stones cause changes in the cells lining the ducts. Early diagnosis of liver stones is advised. (Consumer Summary produced by Reliance Medical Information, Inc.)

With the continuous development of Evs (electric vehicles) and new energy, smart BESS (battery energy storage system) charging stations came into being, and the EV battery testing technology is particularly important. Improving the stability of the vehicle can not only reduce the accident rate of the vehicle, reduce casualties and economic losses, but also improve the traffic conditions and people’s living standards. To ensure safe battery use and reduce average lifecycle costs, EV battery inspection methods with real-time implementation are required in different applications. Therefore, this paper discusses the methods for the SOC (state of charge), SOH (state of health), and remaining life prediction of EV batteries, followed by an analysis of potential application techniques and practical application scenarios. A complete solution for the whole life cycle online inspection and fault detection of EV batteries is proposed, using the SOC, SOH algorithm and drive method for special scenario application described in the paper. In addition, a future life prediction method that may be applied to battery detection during charging of EV in EV charging stations with PV can be obtained based on the EV and battery aging model. And this paper provides a comparative analysis of the EV battery test reports provided by two charging post operators and gives corresponding charging recommendations. Finally, the future development prospects and applications of the testing technologies are extended by the real charging scenarios of EVs.

Repairing osteoporotic bone defects is still a major clinical challenge. Recent studies have revealed that immune response is also essential in osteogenesis. The intrinsic inflammatory response of the host, especially the M1/M2 polarization status and inflammatory secretory function of macrophages, can directly affect osteogenic differentiation. Therefore, in this study, an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate (Ng-m-SAIB) system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects. The results of both in vitroand in vivoexperiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2, thereby forming a favorable microenvironment for osteogenesis. The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of the osteoporotic model mouse (the senescence-accelerated mouse-strain P6). Together, these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favorable osteo-immunomodulatory effects.

It is known that phytohormone auxin affects floral sexual determination in monoecious Cucurbitaceae such as cucumber and melon. TRANSPORT INHIBITOR RESPONSE 1 (TIR1) was first identified in Arabidopsis thalianaas the auxin receptor but few reports have correlated it with fruit initiation and development. As the first step to understanding the regulatory mechanism of auxin in flower sex expression, fruit set, and fruit development in bitter gourd, a TIR1ortholog named McTIR1, was isolated and characterized in monoecious bitter gourd (Momordica charantiaL.). The translation start codon locates in the second exon of McTIR1. Based on phylogenetic analysis, the similarity of deduced amino acid sequence was closer between the McTIR1 and AtTIR1 than between McTIR1 and AUXIN SIGNALING F-BOX (AFB) family. Northern analysis indicated McTIR1expressed in the early fruit developmental stages of bitter gourd. The McTIR1mRNA was most abundant in young leaves and stems and lowest in roots of bitter gourd. Expression of McTIR1was further characterized using transcriptional fusion construct containing β-glucuronidase reporter gene fused to the gene promoter and 5′-untranslated region of McTIR1. The expression of McTIR1promoter decreased dramatically during the late stages of pistil development in transgenic tobacco. These results indicate that expression of auxin receptor McTIR1is associated with the pistil development of unisexual flowers in bitter gourd.

It is an urgent matter to relieve the side effects induced by chemotherapy. In recent years, auricular acupoints therapy, which is a nursing technique used in traditional Chinese medicine (TCM), has been used on many patients who are undergoing chemotherapy without causing any side effects. Furthermore, it has a good efficacy and is inexpensive.

Background: Vascular inflammation critically regulates endothelial pathophenotypes, yet causative mechanisms remain incompletely defined, particularly in pulmonary arterial hypertension (PAH). Immune dysregulation and metabolic reprogramming are recognized tenets of PAH pathogenesis, but a unifying theory connecting the two has not been established.Methods & Results:Guided by an unbiased, metabolome-wide association study from the multicenter PAH Biobank cohort (N=2,666) that identified a proinflammatory sterol and bile acid metabolite plasma signature significantly associated with PAH mortality (adjusted Pvalues<1.1x10-6), we found in pulmonary arterial endothelial cells (ECs) that induction of the nuclear receptor coactivator 7 (NCOA7) tempered the generation of proinflammatory sterols by bolstering lysosomal acidification and constraining EC immunoactivation. Conversely, reduced NCOA7 promoted lysosomal dysfunction, resulting in sterol- and bile acid-driven inflammation and EC phenotypes consistent with PAH. Notably, the common variant intronic SNP rs11154337 in NCOA7was found to control NCOA7 levels, lysosome activity, sterol and bile acid production, and EC immunoactivation in isogenic, CRISPR-Cas9, SNP-edited, iPSC-derived ECs, indicating a potentially widespread genetic predisposition to NCOA7 deficiency. Correspondingly, SNP rs11154337 was associated with PAH severity as noted by six-minute walk distance (P=0.0130, β=58.15, 95% CI [14.45-119.36]) and mortality (P=0.0250; hazard ratio=0.4368, 95% CI [0.21-0.90]) in an independent, single-center PAH cohort (N=93). In vivo, mice deficient for Ncoa7or treated with exogenous 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA)—chosen as a representative metabolite from the sterol signature associated with mortality in the PAH Biobank—demonstrated worsened hemodynamic and histological indices of PAH.Conclusions:Our work establishes a genetic and metabolic paradigm that links lysosomal biology and sterol and bile acid processes with EC inflammation. This paradigm carries broad implications not only on molecular diagnostic and therapeutic development in PAH but also in other vascular disorders dependent upon acquired and innate immune regulation.

The hydrogen induced cracking (HIC) behavior of a high deformability pipeline steel was investigated with three different dual-phase microstructures, ferrite and bainite (F+B), ferrite and martensite/austenite islands (F+M/A) and ferrite and martensite (F+M), respectively. The HIC test was conducted in hydrogen sulfide (H2S)-saturated solution. The results showed that the steels with F+B and F+M/A dual-phase microstructures had both higher deformability and better HIC resistance, whereas the harder martensite phase in F+M microstructure was responsible for the worst HIC resistance. The band-like hard phase in dual-phase microstructure was believed to lead to increasing susceptibility to HIC.

In this study, hydrogen-induced cracking (HIC) and sulfide stress corrosion cracking (SSC) behaviors of high-strength pipeline steels in four different strength grades (X70, X80, X90 and X100) with the microstructure of acicular ferrite were estimated. The results showed that both of X70 and X80 steels exhibited better HIC resistance, and their susceptibility to HIC increased with the strength grade. HIC parameters, including cracking length ratio, cracking thickness ratio (CTR) and cracking sensitivity ratio, were all increased, and among these, the CTR increased most, with the increase in the strength grade. HIC was found to initiate and grow along the hard boundaries such as large size martensite/austenite (M/A) islands and bainitic ferrite. In addition, the density of hydrogen-induced blister on the steel surface was increased with the decrease in pH value for the same-grade pipeline steels. SSC susceptibilities of X80, X90 and X90-C were revealed to subsequently decrease, which was related to the large size M/A islands.

This study aims to describe the preparation and characterization of SiO2/TiO2 core-shell particles. In order to prepare the homogenous SiO2/TiO2 inorganic compounds by sol-gel process, SiO2 particles were used as the core, AcAc served as a chelating agent to chelate with TTIP (which was used as the precursor to TiO2), and PEG was added to stabilize the hydrolysis/condensation process. In addition, the ionic surfactant (SDS) and the nonionic surfactant (PVP) dispersed the core-shell particles. In order to improve the crystal structure, a high temperature was used to calcine the core-shell particles. The influence of various reaction parameters on the size, morphology and composition of the particles was also investigated. The properties of the particles were analyzed by electron microscopy, fourier transform infrared analysis, thermogravimetric analysis and powder X-ray diffraction.

The long-term survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is very low. Cancer stem cells have been identified in PDAC based on the expression of the surface markers CD24, CD44, CD133, and epithelial specific antigen. The prognosis of PDAC may be related to the presence or absence of tumor cells with cancer stem cell surface markers.

Objective To assess the correlations between atherosclerotic plaque characteristics and inflammatory activity by combined use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI).Methods Patients underwent 18F-FDG PET/CT and MRI. Target/background ratios (TBR) of axial sections were determined from mean standard uptake values (SUV). Correlations between TBR and mean vessel wall thickness, total vessel area, lumen area, vessel wall area and normalized wall index were calculated. Plaque types were defined as calcified, collagen, lipid or haemorrhage. Plaques were also classified as thick, thin, or ruptured fibrous cap.Results The study included 31 patients (1178 plaque slices). There was a significant decrease in TBR values across the fibrous cap groups, such that ruptured > thin > thick. Lipid and haemorrhage plaques had significantly higher TBR than calcification and collagen plaques. There were weak positive correlations between TBR and mean vessel wall thickness, vessel wall area and normalized wall index.Conclusions Thin or ruptured plaques, lipid-rich plaques and haemorrhagic plaques possess high inflammatory activity. The combination of 18F-FDG PET/CT and MRI could be useful for qualitative and quantitative diagnosis of carotid atherosclerotic plaques.

The properties of charmonium in a strongly coupled QCD-like plasma at finite momentum are studied. This is based upon a "bottom-up" holographic model which has been previously shown to reproduce charmonium phenomenology in vacuum and give a reasonable dissociation temperature at zero momentum. The finite momentum spectral functions are presented and found to be consistent with recent lattice results. The in-medium dispersion relation and momentum dependence of the decay width of J/? have also been investigated. We find no signature of a subluminal limiting velocity from the dispersion relation, while we note that the dissociation temperature decreases with momentum faster than previous holographic models. Based upon the dissociation temperature, a maximum momentum for J/? in-medium is identified and its phenomenological implications on J/? suppression are discussed. [ABSTRACT FROM AUTHOR]

The microstructural evolutions of advanced 9–12%Cr ferrite/martensite heat-resistant steels used for power generation plants are reviewed in this article. Despite of the small differences in chemical compositions, the steels share the same microstructure of the as-tempered martensite. It is the thermal stability of the initial microstructure that matters the creep behavior of these heat-resistant steels. The microstructural evolutions involved in 9–12%Cr ferrite heat-resistant steels are elaborated, including (1) martensitic lath widening, (2) disappearance of prior austenite grain boundary, (3) emergence of subgrains, (4) coarsening of precipitates, and (5) formation of new precipitates, such as Laves-phase and Z-phase. The former three microstructural evolutions could be retarded by properly disposing the latter two. Namely improving the stability of precipitates and optimizing their size distribution can effectively exert the beneficial influence of precipitates on microstructures. In this sense, the microstructural stability of the tempered martensite is in fact the stability of precipitates during the creep. Many attempts have been carried out to improve the microstructural stability of 9–12%Cr steels and several promising heat-resistant steels have been developed.

A superconducting qubit coupled to a microwave resonator provides a controllable system that enables fundamental studies of light-matter interactions. In the dispersive regime, photons in the resonator exhibit induced frequency and phase shifts which are revealed in the resonator transmission spectrum measured with fixed qubit-resonator detuning. In this static detuning scheme, the phase shift is measured in the far-detuned, linear dispersion regime to avoid measurement-induced demolition of the qubit quantum state. Here we explore the qubit-resonator dispersive interaction over a much broader range of detunings, by using a dynamic procedure where the qubit transition is driven adiabatically. We use resonator Wigner tomography to monitor the interaction, revealing exotic nonlinear effects on different photon states, e.g., Fock states, coherent states, and Schrödinger cat states, thereby demonstrating a quantum Kerr effect in the dynamic framework. [ABSTRACT FROM AUTHOR]

PURPOSE:Our preliminary report of imatinib mesylate (IM) in gastrointestinal stromal tumor (GIST) patients detailed a high response rate; however, the long-term result is still unknown. We conducted an analysis of Taiwan advanced inoperable/metastatic GIST patients treated on IM regarding survival, pattern of failure, potential prognostic factors, and mutational status. PATIENTS AND METHODS:From 2001 to 2010, patients with pathologically proven advanced inoperable/metastatic GIST receiving IM were enrolled onto this study. Data on KITmutational status, measurable tumor size, and other potential prognostic factors were prospectively collected. Patients were followed up for a median of 33.6 months. RESULTS:There were 171 patients (106 men and 65 women) with response rate, and their clinical benefit for IM was 57.3% and 87.1%, respectively. Median progression-free survival (PFS) and overall survival (OS) for these 171 patients are 37.6 and 71.0 months, respectively. Of 171 patients, 120 (70.2%) remained on long-term IM use. Poor performance status, tumor larger than 11.5 cm, primary resistance, and the presence of an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor larger than 11.5 cm were three independently unfavorable predictors. CONCLUSIONS:The median PFS and OS of 171 GIST patients are 37.6 and 71.0 months, respectively. Poor performance status, tumor size larger than 11.5 cm, primary resistance, and an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor size larger than 11.5 cm were three independent unfavorable predictors.

We have successfully expanded the library of amino–NHCs with varying substituents on the amine group, leading to insight about the instability of NHCs arising from the intermolecular interaction of the dangling amine side‐arm. However, the pendant amine plays an important role with respect to the catalytic process, resuscitating the catalytic activity of unsaturated NHC’s through a synergistic effect invoked by the secondary amine. This proof of concept allows us to expand the spectrum of catalysis to CC, as well as CB bond formation.

Field emitter arrays (FEAs) were developed using carbon nanotubes (CNTs) as electron emission sources. The CNTs were grown using a selective-positioning technique with a resist-protection layer. The light emission properties were studied through the electron emission of the CNTs on patterned islands, which were modulated with island diameter and spacing. The electron emission of CNT arrays with 5 μm diameters and 10 μm heights increased with increased spacing (from 10 μm to 40 μm). The electron emission current of the 40-μm-island-spacing sample showed a current density of 1.33 mA/cm2 at E = 11 V/μm, and a turn-on field of 7 V/μm at 1 μA emission current. Uniform electron emission current and light emission were achieved with 40 μm island spacing and 5 μm island diameter.