Measurement Method for Contact Wire Wear Based on Stereovision.

The contact wire wear is an important parameter to ensure the safety operation of electric railways. The contact wire may break if the wear is serious, which leads to transportation interruptions. This study proposes an optical measurement method of contact wire wear, using stereovision technology. The matching method of stereovision based on line-scan cameras is proposed. A lookup-table method is developed to exactly determine the image resolution caused by the contact wire being in different spatial positions. The wear width of the contact wire is extracted from catenaries' images, and the residual thickness of the contact wire is calculated. The method was verified by field tests. The round-robin tests of the residual thickness at the same location present excellent measurement repetitiveness. The maximum difference value between dynamic test results and ground measurement results is 0.13 mm. This research represents a potential way to implement condition-based maintenance for contact wire wear in the future in order to improve the maintenance efficiency and ensure the safety of catenary infrastructure.

Improved Luminous Efficiency of AgInS2 Quantum Dots and Zeolitic Imidazolate Framework-70 Composite for White Light Emitting Diode Applications.

The application of multiple quantum dots (QDs) in the field of white light emitting diodes (WLEDs) is still an important challenge due to their low luminous efficiency and quenching phenomenon. In this paper, we prepared AgInS2 QDs/zeolitic imidazolate framework-70 (AIS/ZIF-70) composite by a microwave hydrothermal method. Owing to the high porosity and stability of ZIF-70, it could effectively prevent quenching issues due to the aggregation of QDs. Since the ZIF-70 and QDs were chemically bonded, the formation of the ZnS layer could effectively passivate the surface defect and thus the quantum yield reached 21.49 % in aqueous solution. The luminous efficiency (LE) of the assembled AIS/ZIF-based WLED was reinforced by 6.8 times with a molar ratio of AgIn/Zn=18, i. e. at 5.26 % molar fraction of ZIF-70. Moreover, the color rendering index (CRI) and correlated color temperature (CCT) of AIS/ZIF-based WLED were 84.3 and 3631 K, respectively, indicating its potential application in solid-state lighting.

The Transport and Uptake of Resveratrol Mediated via Glucose Transporter 1 and Its Antioxidant Effect in Caco-2 Cells.

Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of H2O2-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of H2O2-induced oxidative damage in Caco-2 cells. In the Caco-2 cell transport model, it was observed that the uptake and transport of resveratrol (10, 20, 40, and 80 µM) were time dependent and concentration dependent. Different temperatures (37 °C vs. 4 °C) could significantly affect the uptake and transportation of resveratrol. The apical to basolateral transport of resveratrol was markedly reduced by STF-31, a GLUT1 inhibitor, and siRNA intervention. Furthermore, resveratrol pretreatment (80 µM) improves the viability of Caco-2 cells induced by H2O2. In a cellular metabolite analysis combined with ultra-high performance liquid chromatography-tandem mass spectrometry, 21 metabolites were identified as differentials. These differential metabolites belong to the urea cycle, arginine and proline metabolism, glycine and serine metabolism, ammonia recycling, aspartate metabolism, glutathione metabolism, and other metabolic pathways. The transport, uptake, and metabolism of resveratrol suggest that oral resveratrol could prevent intestinal diseases caused by oxidative stress.

[Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder].

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Tailoring transmission window in a dynamic way with a multi-degree-of-freedom.

With the rapid development of wireless technology, the revolution of tailoring transmission window in dynamic way for the next generation communication systems is urgently required. However, the degree-of-freedom for switching transmission spectra of an effective medium still needs further investigation. Here, we propose a paradigm of solving this difficult academic issue via the method of bias-voltage-driven. Leveraging PIN diodes and varactor diodes into the predesigned positions of plasmonic meta-structures, the macro-control of transmission windows switch and the detailed dispersion manipulation can be separately achieved by synergy modulation of feed networks. Both the numerical simulations and experimental verifications are conducted to support the effectiveness of the proposed method. Significantly, the proposed paradigm presents great potential for applications in intelligent radome, adaptive communication systems, and other EM scenarios with multi-degree-of-freedom.

Polarization meta-converter for dynamic polarization states shifting with broadband characteristic.

Polarization, as an important property of light, has been widely discussed in modern detecting and radar systems. A polarization converter that can be used to achieve dynamic control is regarded as an excellent alternative for implementing the integrated functionalities of communication and stealth. In this work, we propose a paradigm of meta-converter for dynamic polarization states shifting from linear-to-linear (LTL) to linear-to-circular (LTC) polarization. The strategy is achieved by loading voltage-controlled PIN diodes on the double-arrows metallic meta-resonators. The operation modes can be switched by changing the bias voltage. When the PIN diodes are turned on, the polarization meta-converter (PMC) will reflect and convert a linearly polarized electromagnetic (EM) wave into a circularly polarized one in 5.6-15.5 GHz with an axial ratio (AR) below 3dB. When the PIN diodes are turned off, the PMC will reflect and convert a linearly polarized EM wave into the orthogonal counterpart in 7.6-15.5 GHz with a polarization conversion ratio (PCR) over 88%. Simulations and experimental results show a good agreement, which manifests the feasibility of our proposed meta-converter. Moreover, the proposed PMC has great potential for polarization-dependent communication and stealth systems.

Investigation of migration rule of rainwater for sponge city roads under different rainfall intensities.

Urban development and climate change have led to severe waterlogging in cities. To study the degree of mitigation of urban waterlogging using the design of sponge city roads, this study employed No. 9 Road in the Sino-German Eco-park. By establishing the scaled physical model, the pavement structure of the sponge city road was optimized. Furthermore, water migration (seepage, impoundment, and drainage) rule was obtained under different rainfall intensities using the optimal pavement scheme. The following conclusions were drawn from the studies. Good permeability of the sidewalk surface structure is conducive for rainwater collection. The sponge urban road rainwater collection and utilization system could absorb up to 88% of rainwater under the rainfall intensity of 173 mm (extra heavy rain), and could absorb up to 100% of rainwater under heavy rain conditions. The seepage volume increased exponentially with the rise in rainfall intensity, and the amount of water storage increased linearly with the rainfall intensity. These results can provide guidance for safety early warning of urban waterlogging on No. 9 Road in the Sino-German Eco-park and deeper insights in the design of sponge city roads.

Active circular dichroism coding meta-mirror for flexible beam-forming and dynamic amplitude control.

Equipped with the capability of simultaneous phase and amplitude modulation, the chiral metasurfaces have broken through the weak chiroptical responses of natural media, giving birth to a number of unprecedented phenomena. However, the performance of passive metasurface is inadequate to realize dynamic manipulation to fit the diverse and changeable operation requirements, which would damage their engineering applications. Here, a circular dichroism meta-mirror consisting of Archimedean spiral-based meta-atoms is proposed to achieve dynamic scattering modulation. Combining the strategy of loading active element, the chiroptical responses of a metasurface is smoothly controlled. By controlling bias voltages, continuous scattered reflection amplitude steering can be achieved for the designated spin state while the orthogonal spin state can hardly be influenced. With the assistance of Pancharatnam-Berry phase principle, the metasurface possesses the capability of tailoring waves in coded manner. We experimentally verify the proposed strategy by a 1-bit checkerboard meta-mirror for four-beam scattering pattern. Importantly, the proposed paradigm may find applications in spin-sensitive systems and adaptive camouflage.

Circular dichroism assisted metadevice for efficient transmission and broadband absorption.

Owing to the intriguing capability of manipulating electromagnetic (EM) properties, the metasurface has aroused great attention of researchers and promoted its applications in EM invisibility. However, there are strong demands to provide an efficient transparent window for signals transmitting in EM invisibility devices. Here, we propose a scheme of a circular dichroism assisted metadevice to provide efficient transmission and broadband absorption in microwave frequencies. By employing chiral meta-atoms to introduce a strong asymmetric response for circularly polarized waves, a chiral metadevice for spin-selective absorption with an efficient transmission is presented. Then, we couple four chiral atoms into a polarization-insensitive atom pair, thus the achiral metadevice presents an identical high-efficiency absorption for both the x- and y-polarized wave. Here, both the chiral and achiral metadevices are realized by loading the metasurface-based absorber on a bandpass frequency selective surface. A proof-of-prototype is fabricated to verify the achiral design. The simulated and experimental results have demonstrated wideband, high-efficiency, polarization-insensitive absorption and high in-band transmission. Interestingly, the proposed paradigm can not only provide the potential for chirality-enhanced absorber design but also may trigger applications in spin-dependent systems, stealth antenna systems, and EM camouflage devices.

Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

RNA virome screening in diverse but ecologically related citrus pests reveals potential virus-host interactions.

As an evergreen ecosystem, citrus orchards have specialized pest species and stable ecological homeostasis; thus, they provide an ideal model for investigating RNA viromes in diverse but ecologically related species. For this purpose, we collected specialized citrus pests from three classes of invertebrates, Insecta, Arachnida, and Gastropoda and we constructed two kinds of libraries (RNA and small RNA) for the pests by deep sequencing. In total, six virus-derived sequences were identified, including four Picornavirales, one Jingchuvirales and one Nidovirales. The picornavirus-derived small RNAs showed significant small RNA peaks and symmetric distribution patterns along the genome, which suggests these viruses infected the hosts and triggered host antiviral immunity RNA interference. Screening of virus-derived sequences in multiple species of citrus pests (n = 10 per species) showed that Eotetranychus kankitus picorna-like virus and Tetranychus urticae mivirus may be present in multiple pests. Our investigation in citrus pests confirmed that RNA viruses revealed by metagenomics could impact host immunity (e.g. RNAi). An approach with parallel deep sequencing of RNAs and small RNAs is useful not only for viral discoveries but also for understanding virus-host interactions of ecologically related but divergent pest species.

Quantitative proteomics suggest a potential link between early embryonic death and trisomy 16.

Activation of extracellular signal-regulated kinase (ERK) signalling, alteration of the uterine microenvironment and a reduction in human chorionic gonadotrophin production have been linked with fetal trisomy 16-induced early embryonic death (EED). However, the detailed biological mechanism of EED remains unclear. Using quantitative proteomics we successfully screened differentially expressed proteins in the villous tissues from patients with EED and fetal trisomy 16 (EEDT16), patients with EED but normal fetal chromosomes (EEDNC) and patients undergoing elective abortion with normal fetal chromosomes (EANC) as the reference group. Compared with the reference group, we identified 337 and 220 differentially expressed proteins in EEDT16 patients and EEDNC patients respectively; these were involved in critical biological processes including immune response, superoxide metabolism, inflammatory responses and so on. We found that differential expression of immunological function-related molecules, such as human leukocyte antigen-g (HLA-G), HLA-C, Fc Fragment Of IgG Receptor III (FcγR III), also named CD16, interleukin 18 (IL-18) and transforming growth factor ß1 (TGF-ß1), might induce EED in both EEDT16 and EEDNC patients. More severe immunological dysfunction was observed in EEDT16 patients than that in EEDNC patients. Furthermore, differential expression of implantation and invasion-related molecules, such as cytochrome b-245 light chain (CYBA), neutrophil cytosol factor 2 (NCF2), Mitogen-activated protein kinase kinase kinase 4 (MAP3K4), matrix metalloproteinase 2 (MMP2), MMP9 and tumour necrosis factor α (TNF-α) might induce EED in both EEDT16 and EEDNC patients, although more severe dysfunction in the implantation and invasion ability of villous tissues was observed in EEDT16 patients.

Three novel RNA viruses in the spider mite Tetranychus urticae and their possible interactions with the host RNA interference response.

As a polyphagous herbivore, the two-spotted spider mite Tetranychus urticae is engaged with various plant hosts and interacts with diverse organisms that share the same ecological niche. Thus, T. urticae faces frequent challenges from viral infections. However, the RNA viruses of T. urticae are still unknown. Here, we constructed two libraries (~8 Gb for RNA and ~10 Mb for small RNA) from a strain of T. urticae using deep sequencing, and identified three novel RNA viruses from the families Kitaviridae, Dicistroviridae, and Chuviridae. Among them, the Kitaviridae and Dicistroviridae viruses presented a possible interaction pattern with the host RNA interference pathway.

An LC-MS/MS method for the quantification of diclofenac sodium in dairy cow plasma and its application in pharmacokinetics studies.

An LC-MS/MS method with internal standard tolfenamic acid for determining diclofenac sodium (DCF) in dairy cow plasma was developed and validated. Samples were processed with protein precipitation by cold formic acid-acetonitrile. Determination of DCF was performed using LC-ESI+ -MS/MS with the matrix-matched calibration curve. The results showed that the method was sensitive (LOD 2 ng mL-1 , LOQ 5 ng mL-1 ), accurate (97.60 ± 5.64%), precise (<10%) and linear in the range of 5-10,000 ng mL-1 . A single intravenous (i.v.) or intramuscular (i.m.) administration of 5% diclofenac sodium injection at a dose of 2.2 mg kg-1 was performed in six healthy dairy cows according to a two-period crossover design. The main pharmacokinetic (PK) parameters after a single i.v. administration were as follows: t1/2ß , 4.52 ± 1.71 h; AUC, 77.79 ± 16.76 h µg mL-1 ; mean residence time, 5.16 ± 1.11 h. The main PK parameters after a single i.m. administration were as follows: Tmax , 2.38 ± 1.19 h; Cmax , 7.46 ± 1.85 µg mL-1 ; t1/2ß , 9.46 ± 2.86 h; AUC 67.57 ± 13.07 h µg mL-1 . The absolute bioavailability was 87.37 ± 5.96%. The results showed that the diclofenac sodium injection had PK characteristics of rapid absorption and slow elimination, and high peak concentration and bioavailability in dairy cows, and that the recommended clinical dosage of diclofenac sodium injection is 2.2 mg kg-1 .

Molecular characterization of ecdysis triggering hormone and its receptor in citrus red mite (Panonychus citri).

Neuropeptide ecdysis triggering hormone (ETH) plays crucial roles in invertebrates by activating a G protein-coupled receptor (GPCR), the ecdysis triggering hormone receptor (ETHR), which has been intensively investigated in Hexapoda. However, the molecular characterization of ETH and ETHR in Chelicerata remains unknown. In this study, we identified and characterized the full-length cDNA of ETH and ETHR in citrus red mite Panonychus citri (McGregor). Phylogenetic analysis indicated that PcETHR was closely related to the insect ETHR subtype B. A calcium mobilization-based functional assay showed that PcETH activated the PcETHR in a dose-dependent manner. Furthermore, a sharp upregulation of PcETH before ecdysis was observed by quantitative real-time PCR (qRT-PCR), and it revealed a tight correlation of ETH signaling and the molting process. These are the first insights into the molecular characterization of ETH and its receptor in mites as P. citri. Our work provides basic information of the ETH and ETHR in P. citri and lays a solid foundation for further physiological functions to better understand the ETH signaling system in mites.

Cellular Metabolomics Reveal the Mechanism Underlying the Anti-Atherosclerotic Effects of Aspirin Eugenol Ester on Vascular Endothelial Dysfunction.

Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to different treatments. Pretreatment of HUVECs with AEE significantly ameliorated H2O2-induced apoptosis, the overexpression of E-selectin and VCAM-1, and the adhesion of THP-1 cells. Putative endogenous biomarkers associated with the inhibition of endothelial dysfunction were identified in HUVECs pretreated with AEE in the absence or presence of H2O2, and these biomarkers were involved in important metabolic pathways, including amino acid metabolism, carbohydrate metabolism, and glutathione metabolism. Moreover, in vivo, AEE also significantly reduced vascular endothelial dysfunction and decreased the overexpression of VCAM-1 and E-selectin. Based on our findings, the mechanism underlying the anti-atherosclerotic effects of AEE might be related to a reduction in vascular endothelial dysfunction mediated by ameliorating alterations in metabolism, inhibiting oxidative stress, and decreasing the expression of adhesion molecules.

UPLC-Q-TOF/MS-Based Plasma Metabolomics to Evaluate the Effects of Aspirin Eugenol Ester on Blood Stasis in Rats.

Aspirin eugenol ester (AEE) is a novel compound that is formed from the esterification of aspirin (acetylsalicylic acid (ASA)) and eugenol. This study aimed to investigate the effects of AEE on blood stasis in rats and to characterize the underlying mechanisms using a plasma metabolomic study. The results indicate that AEE and ASA could modulate whole blood viscosity (WBV), plasma viscosity (PV), blood coagulation parameters, platelet count, platelet aggregation, lactate dehydrogenase (LDH), creatinine (CR) and the levels of thromboxane A2 (TXA2) and 6-keto prostaglandin F1α (6-keto-PGF1α). The metabolic profiles of the plasma samples from all groups were clearly separated in the score plots. Nineteen potential metabolites were selected and identified, and disordered levels of these metabolites could be regulated by AEE and ASA. Pathway analysis showed that the mechanism of action of AEE on blood stasis might be principally related to the metabolism of amino acid, fatty acid, energy and glycerophospholipid. The above results indicate that AEE protected the rats against blood stasis, and that this effect might have been caused by the anticoagulation activity of AEE and its abilities to maintain a balance between TXA2 and PGI2, reduce blood viscosity, inhibit platelet aggregation and normalize the plasma metabolic profile.

Expression dynamics of key ecdysteroid and juvenile hormone biosynthesis genes imply a coordinated regulation pattern in the molting process of a spider mite, Tetranychus urticae.

In insects, the ecdysteroid 20-hydroxyecdysone coordinates with juvenile hormone (JH) to regulate the process of molting, development and metamorphosis; however, this interaction is still unclear in the mites. In this study, we investigated the gene related to ecdysteroid and JH biosynthesis pathways, including four ecdysteroid and 11 JH biosynthesis genes. We examined their expression patterns during molting of different developmental stages of the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), an important agricultural pest that feeds on more than 1100 plant species. The expression of ecdysteroid biosynthesis Halloween genes exhibited a positive zigzag-like pattern, with a peak after 8 h of molting and a drop 8 h after entering each quiescent stage. In contrast, JH biosynthesis genes expression displayed a negative zigzag-like pattern, with a peak at 8 h after entering each quiescent stage and a drop after 8 h of each molting. These opposite patterns imply that ecdysteroid and JH expression is coordinated during the developmental transition. Our data provide an initial perspective on the co-expression of ecdysteroid and JH biosynthesis genes to regulate this important developmental process in the two-spotted spider mite.

Aspirin eugenol ester regulates cecal contents metabolomic profile and microbiota in an animal model of hyperlipidemia.

BACKGROUND: Hyperlipidemia, with an increasing of prevalence, has become one of the common metabolic diseases in companion animal clinic. Aspirin eugenol ester (AEE) is a novel compound that exhibits efficacious anti-hyperlipidemia activities. However, its mechanisms are still not completely known. The objective of present study was to investigate the intervention effects of AEE on cecal contents metabonomics profile and microbiota in hyperlipidemia rats. RESULTS: Three groups of rats were fed with a control diet, or high fat diet (HFD) containing or not AEE. The results showed the beneficial effects of AEE in HFD-fed rats such as the reducing of aspartate aminotransferase (AST) and total cholesterol (TCH). Distinct changes in metabonomics profile of cecal contents were observed among control, model and AEE groups. HFD-induced alterations of eight metabolites in cecal contents mainly related with purine metabolism, linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and pyrimidine metabolism were reversed by AEE treatment. Principal coordinate analysis (PCoA) and cluster analysis of microbiota showed altered patterns with distinct differences in AEE group versus model group, indicating that AEE treatment improved the negative effects caused by HFD on cecal microbiota. In addition, the correction analysis revealed the possible link between the identified metabolites and cecal microbiota. CONCLUSIONS: This study showed regulation effects of AEE on cecal contents metabonomics profile and microbiota, which could provide information to reveal the possible underlying mechanism of AEE on hyperlipidemia treatment.

Differential degradation rate and underlying mechanism of a collagen/chitosan complex in subcutis, spinal cord and brain tissues of rat.

Degradation rate is an important index for evaluating biomaterials. The authors' aim was to determine whether the degradation rate of biomaterials is different in distinct tissues and to clarify the underlying mechanism of degradation. The collagen-chitosan (CG-CS) composite scaffolds were prepared using freeze-drying technology. The porosity, water absorption and swelling ratio of the scaffolds were tested in vitro. The scaffolds were implanted into the subcutis, spinal cord and brain tissues of SD rats, the rate of degradation was assessed by continuous monitoring of weight loss, the pathological changes of target areas were observed by histological staining, and matrix metalloproteinase 9 (MMP-9) and lysozyme were detected at the rapid stage of degradation of the scaffolds. Physical and chemical property testing confirmed that CG-CS composite scaffold components can meet the biological requirements of in vivo transplantation. The in vivo experimental results showed that the scaffolds were completely absorbed in the subcutis at 12 days, the scaffolds in the spinal cord and brain groups exhibited progressive mass loss starting from the 3rd week, and a substantial fraction of the scaffold was degraded at 12 weeks. HE staining found that compared with the spinal cord and brain groups, macrophages and capillaries appeared earlier in the subcutis group, and the number was significantly higher (P < 0.05). Western blot analysis showed that the MMP-9 and lysozyme levels in the subcutis were higher than those in the spinal cord and brain (P < 0.05). The results of in vivo experiments demonstrated that the CG-CS scaffold has good biocompatibility and biodegradability, while the rate of degradation was significantly different between the three tissues at the same time point. Macrophage behavior and vascularization in different parts of the body may result in control over the balance of degradation and reconstruction.