Search

Application of zero-valent iron (ZVI) has become one of the most promising innovative technologies for the remediation of environmental pollutants. However, ZVI may suffer from the low intrinsic reactivity toward refractory pollutants, which seriously restricts its practical application in fields. Therefore, strategies have been developing to enhance the reactivity of ZVI. Until now, the most commonly used strategies include pretreatment of ZVI, synthesis of highly-active ZVI-based materials and additional auxiliary measures. In this review, a systematic and comprehensive summary of these commonly used strategies has been conducted for the following purposes: (1) to understand the fundamental mechanisms of the selected approaches; (2) to point out their advantages and shortcomings; (3) to illustrate the main problems of their large-scale application; (4) to forecast the future trend of developing ZVI technologies. Overall, this review is devoted to providing a fundamental understanding on the mechanism for enhancing the reactivity of ZVI and facilitating the practical application of ZVI technologies in fields. [Display omitted] • Recent advances on strategies to enhance the reactivity of ZVI are reviewed. • The mechanism, advantages and shortcomings of the enhancing strategies are summarized. • An up-to-date prospective trend toward enhancing the reactivity of ZVI is drawn. • Main problems and future needs on enhancing the reactivity of ZVI are proposed. [ABSTRACT FROM AUTHOR]

Antioxidant peptides obtained from alcalase-hydrolyzed porcine plasma albumin (AHA, MW <3 kD) were purified by consecutive chromatographic methods, and the antioxidative effects of unpurified AHA and sub-fractions from the first step of HPLC (P4, MW <1.5 kD) and second step of HPLC (P4b, MW <1.5 kD) were evaluated in cell line. P4 exhibits the highest reducing power (0.89) than its further purified fraction P4b (0.69) and unpurified AHA (0.5). Moreover, a concentration of 100 mg/ml of P4 also demonstrates better protective effect on HO-induced oxidative damage and antioxidative enzyme activities (SOD, CAT and GPx) in fibroblast cell than AHA and P4b ( P < 0.05). P4 is composed of seven peptides with MW of 500.19, 524.24, 550.23, 568.19, 656.18, 707.44 and 1,022.70, and their amino acids sequences are identified as LIKQ, LQHK, EQKF, PDIPK, KVPQVS, FKDLGE and EHLREKVL, respectively. All the seven peptides contain lysine, indicating that P4 is lysine-rich peptide fraction. We believe these results, with a more pronounced action of P4 than AHA and P4b plus the characterized amino sequences, would lay the foundation of understanding the antioxidative effect of albumin-derived peptides. [ABSTRACT FROM AUTHOR]

The effects of hydroxyl radicals induced oxidation on water distribution of porcine myofibrillar protein (MP) gels were investigated using nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), and relationship between MP gel properties and water distribution was analyzed with Pearson's correlation. Results of NMR spin-spin relaxation time (T) and MRI suggested that, comparing with unoxidized MP gel, the population of immobile water of gel (P) decreased by 18.81 %, while that of free water (P) increased by 85.56 %, and grey scale value decreased by 18.52 %, after being oxidized with 20 mM HO, respectively. Images of scanning electron microscope (SEM) showed the highest degree of oxidation led to the most coarse and porous gel-network. Gel properties including WHC, whiteness and strength of MP gels decreased by 14.65 %, 2.83 % and 52.74 % after being oxidized with 20 mM HO ( p < 0.05), respectively. Pearson's correlation analysis showed oxidation, gel-properties and NMR results were highly correlated ( p < 0.05). Therefore, we hypothesized that hydroxyl radicals induced oxidation resulted in immobile water shifting to free water partly, thus reduced the abundance of water and gel properties of gels. [ABSTRACT FROM AUTHOR]

To reflect the permeability change of loaded rock, the relationship between the permeability and stress-strain curve of rock was analyzed, and the process the deformation and failure of rock was supposed to be elastic, brittle and plastic. Based on the process the permeability evolution model for rock was presented. In this model the evolution of the permeability for the rock element include; (1) The permeability can be expressed by porosity during elastic deformation phase. (2) In the post-peak stage a shear failure rock element may be represented hydraulically as a unit of rock containing two oblique crossing conjugate fractures. (3) In the post-peak stage a tension failure rock element may be represented hydraulically as a unit of rock containing two orthogonal fractures. Then based on so-called cubic law between smooth parallel plates the permeability evolution model during dilation was presented. In the model the dilation effects of failed element on permeability was considered. Fish function method was adopted to implement the model in FLAC software. The permeability evolution process of a cubic loading rock sample under varied confined stress was simulated. The results show that the model can better reflect the permeability evolution due to elastic deformation or failure. Besides the effect of confined stress on permeability can also be better expressed. [ABSTRACT FROM AUTHOR]

Here, we describe the structural optimization of a known EGFR inhibitor (compound 1) that showed weak off-target activity against RET. Twenty-six analogs of 1 were synthesized. SAR analysis led to the discovery of several compounds that showed considerable potency against the RET-dependent thyroid cancer cell line TT. Kinase inhibitory potency was then measured for the most active compound ( 2u) in the cellular assay. The results showed that 2u is a potent RET inhibitor with an $$\hbox {IC}_{50}$$ value of 7 nM. [ABSTRACT FROM AUTHOR]

WASP homolog associated with actin, membranes and microtubules (WHAMM) is a newly discovered nucleation-promoting factor that links actin and microtubule cytoskeleton and regulates transport from the endoplasmic reticulum to the Golgi apparatus. However, knowledge of WHAMM is limited to interphase somatic cells. In this study, we examined its localization and function in mouse oocytes during meiosis. Immunostaining showed that in the germinal vesicle (GV) stage, there was no WHAMM signal; after meiosis resumption, WHAMM was associated with the spindle at prometaphase I (Pro MI), metaphase I (MI), telophase I (TI) and metaphase II (MII) stages. Nocodazole and taxol treatments showed that WHAMM was localized around the MI spindle. Depletion of WHAMM by microinjection of specific short interfering (si)RNA into the oocyte cytoplasm resulted in failure of spindle migration, disruption of asymmetric cytokinesis and a decrease in the first polar body extrusion rate during meiotic maturation. Moreover, actin cap formation was also disrupted after WHAMM depletion, confirming the failure of spindle migration. Taken together, our data suggest that WHAMM is required for peripheral spindle migration and asymmetric cytokinesis during mouse oocyte maturation. [ABSTRACT FROM AUTHOR]

In this paper, to obtain the dynamics characteristics of non--resonance structure in ultrasonic gear honing, the frequency equations and displacement amplitude equations of the transformer were derived by means of Mindlin's theory and force coupling conditions of the cone horn and moderately thick annular plate. Then, the numerical solutions of the design parameters and displacement amplitudes for transformer were solved by using MATLAB software. The results from finite element analysis (FEA) and dynamical experiment are consistent with the numerical solutions proposed in this paper. [ABSTRACT FROM AUTHOR]

To reflect the effect of confining pressure on the brittleness of the post-peak rock, the degradation angle of post-peak strength of the new parameter was presented. Based on the test data for mudstone of Shanxi in triaxial compression, the linear relationship between the degradation angle and the confining stress was founded. The law between the equivalent plastic shear strain and the degradation angle was presented, and the strain softening model of rock based on the degradation angle was set up. Fish function method within FLAC was used and the numerical code was developed. In numerical case study, the strain softening processes under variable confining pressure for mudstone of Shanxi were modeled. The simulating results accord with experimental data. Those show that the degradation angle is an effective parameter to reflect the effect of confining pressure on the brittleness of the post-peak rock; the model in this paper is reasonable and can be used to model the strain softening processes of post-peak strength rock. [ABSTRACT FROM AUTHOR]

Based on the relevant financial data of 14 tourism listed companies from 2001 to 2009 and by establishing multiregression model, the paper studies the correlation between intangible assets and operating performance and compares contributions to operating performance among three types--hotel type, scenic spot type and comprehensive type by introducing dummy variables. The study results indicate that the contribution of intangible assets to operating performance is significant and positive and their contribution is far greater than that of fixed assets. There exist distinct differences among hotel type, scenic spot type and comprehensive type in terms of their contributions to operating performance. Hotel type is higher than comprehensive type and scenic spot type while comprehensive type is higher than scenic spot type, but it is not statistically significant. Finally, corresponding suggestions are put forward through combining with the practical analysis of reasons. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the effect of peroxisome proliferator activated receptor-γ, (PPARγ) ligand, 15d-PGJ2 on inhibition of T cell proliferation and T cell-mediated osteoclastogenesis, and clarify the possible mechanism. METHODS: T cells from A.actinomycetetemcomitans immunized BALB/c mice were isolated from cervical lymph nodes and T lymphocytes enriched in vitro. At 3-day after 15d-PGJ2 (0,1x10-8, 1x10-7 1x10-6 x 10-5mol/L) induction, T cell proliferation analysis was measured by cintilography, the concentration of RANKL, TNF-α and IL-10 were measured in culture supernatants by ELISA, and osteoclastogenesis of co-culture with RAW 264.7 cell and T lymphocyte supernatants that enriched in vitro by tartrate resistant acid phosphatase (TRAP) staining. SASS 11.0 software package was used for statistical analysis. RESULTS: By 1 x10-5mol/L 15d-PGJ2 induction, T cell ³H incorporation remarkably decreased, the expression of RANKL and TNF-α in the supernatant markedly decreased, significantly different compared with the control group (P<0.05) , but IL-10 was not significantly different, and the numbers of TRAP positive cells decreased, significantly different compared with the control group (P<0.05),which was dose-dependent. CONCLUSIONS: PPARγ ligand 15d-PGJ2 can inhibit ³H incorporation, down-regulate cytokine release, decrease T cell-induced osteoclastogenesis. The data suggest that PPARγ ligand plays an important role in T cell-induced bone resorption. Supported by Natural Science Foundation of Liaoning Province (20092139) and Research Fund of Science and Technology Commission of Shenyang City (F10-149-9-32). [ABSTRACT FROM AUTHOR]

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context. • Treatment with Vinorelbine prevents oocyte meiotic maturation in mice. • Vinorelbine exposure disrupts the dynamics of the spindle and chromosomes in mouse oocytes. • Vinorelbine administration delays APC/C activation by inducing continuous activation of the SAC. • Vinorelbine administration leads to aneuploidy in oocytes. [ABSTRACT FROM AUTHOR]

Previous studies have shown sleep deprivation is increasingly reported as one of the causes of female infertility. However, how and by what relevant mechanisms it affects female fertility remains unclear. In this study, female mice underwent 72 hours of total sleep deprivation (TSD) caused by rotating wheel or 2 different controls: a stationary wheel, or forced movement at night. Even though, there was no significant difference in the number of eggs ovulated by the TSD mice compared to the control groups. Overall levels of estrogen and FSH were lower throughout the estrus cycle. A total of 42 genes showed significant differential expression in GV oocytes after TSD by RNA sequencing (RNA-Seq). These included genes were enriched in gene ontology terms of mitochondrial protein complex, oxidoreductase activity, cell division, cell cycle G1/S phase transition, as well as others. The increased concentrations of reactive oxygen species (ROS) in germinal vesicle (GV) and metaphase II (MII) oocytes from TSD mice were observed, which might be induced by impaired mitochondrial function caused by TSD. The GV oocytes displayed increased mitochondrial DNA (mtDNA) copy number and a significant transient increase in inner mitochondrial membrane potential (Δψm) from the TSD mice probably due to compensatory effect. In contrast, MII oocytes in the TSD group showed a decrease in the mtDNA copy number and a lower Δψm compared with the controls. Furthermore, abnormal distribution of mitochondria in the GV and MII oocytes was also observed in TSD mice, suggesting mitochondrial dysfunction. In addition, abnormal spindle and abnormal arrangement of chromosomes in MII oocytes were markedly increased in the TSD mice compared with the control mice. In conclusion, our results suggest that TSD significantly alters the oocyte transcriptome, contributing to oxidative stress and disrupted mitochondrial function, which then resulted in oocyte defects and impaired early embryo development in female mice. [ABSTRACT FROM AUTHOR]

The detection part plays a considerable role in quantum key distributions (QKD). However, in practical applications, the imperfections of detectors compromise the performance and security of QKD systems, especially when moving into the Gigahertz regime. In this work, we mainly study the impact of afterpulse and dead-time on the key rate of reference-frame-independent quantum key distribution (RFI-QKD) systems. Our simulation results show that the dead-time and the afterpulse effects have significant influences on the key rate at both short and long transmission distances. The present work may provide valuable references for constructing QKD network under practical environments and setups. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim was to describe the clinicopathological features and prognosis of young patients with breast cancer. Patients and Methods: We reviewed the records of 1478 consecutive patients aged ≤50 years with first diagnosis of invasive breast cancer referred to surgery from January 1999 to March 2005. A total of 174 patients were aged <35 years (group I) and 1304 were aged 35–50 years (group II). Results: Compared with patients of group II, patients of group I had a higher percentage of tumors classified as estrogen receptors (ER) negative, progesterone receptors (PR) negative, with a Ki-67 labeling index ≥20% of the cells. The 5-year survival of group I was 78.3% as compared with 84.2% for group II (P = 0.006). Conclusion: Compared with patients aged between 35 and 50 years, patients aged <35 years have a greater chance of having an endocrine-unresponsive tumor and a significantly poor prognosis. [Copyright &y& Elsevier]

Measurement-device-independent quantum key distribution (MDI-QKD) can remove all the side-channel attacks and significantly improve the secure transmission distance. However, the key generation rate is relatively low when taking finite-key-size effect into consideration. In this manuscript, we adopt the latest four-intensity decoy-state scheme combining the heralded pair-coherent sources to study the performance of the MDI-QKD. Moreover, through utilizing joint constraints and collective error estimation techniques, we can obviously improve the performance of practical MDI-QKD systems compared with those using weak coherent sources or heralded single-photon sources. [ABSTRACT FROM AUTHOR]

Quantum digital signature (QDS) is based on the laws of quantum physics, and can provide unconditional security for signing messages between remote multi-party users. To date, different QDS protocols have been proposed and corresponding security analysis has been done. Just most security analyses are directed against signing single-bit messages, and the security cannot be ensured when signing multi-bit messages if one simply puts blocks together. Recently, T.Y. Wang et al. analyzed the security under this situation and gave a solution for eliminating potential eavesdropping attacks. However, its efficiency is relatively low since they need to consume more than 2n-bit signatures to sign a classical n-bit message. In this paper, we propose a high efficient approach for signing multi-bit messages. As a result, the efficiency can be improved with 36.92% when signing a 128-bit message compared with using T.Y. Wang et al.'s method. And the improvement is even larger when signing longer messages. [ABSTRACT FROM AUTHOR]

Considering imperfect experimental conditions, here we give a practical proposal on the decoy-state quantum random number generator with weak coherent sources. In the proposal, three different intensities of light sources are used to estimate the contribution of single-photon pulses. System randomness is characterized and simulated through the minimum entropy. Numerical simulation results show that our new scheme can extract out randomness close to the asymptotic case where the fraction of single-photon pulses are exactly known. Furthermore, a proof-of-principle experimental demonstration is presented, showing excellent agreement between experiment and theory. [ABSTRACT FROM AUTHOR]

COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system. [ABSTRACT FROM AUTHOR]

Background: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Results: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Conclusions: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing. [ABSTRACT FROM AUTHOR]

Currently, mainstream quantum computing simulators are generally based on numerical calculations, which suffer from precision loss, lack of intuitive representation of quantum states, and difficulty in supporting parameterized quantum circuits. Although symbolic quantum computing simulators have been proposed, they are limited in describing parameterized quantum states, constructing custom quantum gates, and integrating with quantum programming environments. To address this issue, this paper proposes a symbolic quantum computing simulator, SymQC. SymQC can use either full amplitude vectors or Dirac symbols to represent quantum states, calculate the equivalent matrix of symbolically parameterized quantum circuits, simulate the evolution of quantum states under quantum circuits, and output the execution results of quantum algorithms in different forms. This paper describes the software structure of SymQC and provides a mathematical proof of a commonly used quantum state update algorithm. Algorithm instances including variational quantum eigensolver (VQE) algorithm are used to verify the ability of SymQC. [ABSTRACT FROM AUTHOR]

Mammalian oocytes are arrested at the diplotene stage of prophase I during fetal or postnatal development. It was reported that cyclin‐dependent kinases (CDK1) was the sole CDK to drive the resumption of meiosis and CDK2 was dispensable for meiosis progression in mouse oocytes according to the conditional knockout studies. However, a recent study showed that CDK2 activity is essential for meiotic division and gametogenesis by means of gene‐directed mutagenesis, which avoids the compensatory activation of other CDKs. Taken the compensatory effect between CDKs after gene knockout, the physiological function of CDK2 activity in oocyte maturation remains unclear. To address this issue, we applied a specific small‐molecule inhibitor to restrain CDK2 activity transiently during oocyte meiotic maturation. Surprisingly, transient inhibition of CDK2 activity severely prevented the meiosis I completion although the meiotic resumption was not affected. Then we found that CDK2 activity was required for establishment of normal spindle and chromosome dynamics. Notably, CDK2 inhibition interrupted the anaphase‐promoting complex/cyclosome (APC/C)‐dependent degradation pathway by maintaining the activation of spindle assembly checkpoint (SAC). Interestingly, CDK2 inhibition prevented the egg activation as well. Overall, our data demonstrate that CDK2 kinase activity is required for proper dynamics of spindle and chromosomes, whose disturbance induces the continuous SAC activation and subsequent inactivation of APC/C activity in oocyte meiosis. [ABSTRACT FROM AUTHOR]

Quantum digital signature is one of the most promising quantum technologies, which can guarantee the authenticity and transferability of messages based on the law of quantum mechanics. Up to date, various protocols have been proposed to make quantum digital signature more practical. However, most of them consider only single protocol and security, neglecting resource allocations in practical applications, especially under the environment of multi-party real-time signatures. Here, we for the first time implement the machine learning method based on the random forest algorithm into the optimization of quantum digital signature systems, and with that, we can predict not only the most suitable protocol, but also the optimal system parameters in real time, with an accuracy of more than 97%. [ABSTRACT FROM AUTHOR]

Highlights: [•] A procedure was set up to produce extracts from chicken bone by hot-pressure extraction. [•] The extracts contain ideal protein and fat, making an excellent substrate for hydrolysis. [•] Hydrolysates of the extracts are a potential suitable nutritional supplement in food industry. [•] Hydrolysis of the extracts (8h) increased the small MW of peptides content by 74times. [Copyright &y& Elsevier]

[Display omitted] • NAEBT not only reduced the CL of meat batter but also improved its texture. • NAEBT improved the WHC of meat batter through its antioxidant properties. • Pre-emulsification enhanced the ability of NAEBT to inhibit protein oxidation. • NAEBT promoted the formation of a dense gel matrix by increasing the β-sheet level. The effect of varying proportions (w/w) of natural aromatic extract of black tea (NAEBT) with pre-emulsification on the water-holding capacity (WHC) of pork meat batter was investigated. The addition of NAEBT significantly reduced the cooking loss (CL) of pork meat batter from 23.95 % to 18.30 % (P < 0.05). Furthermore, NAEBT with pre-emulsification significantly improved the color stability and increased the springiness (P < 0.05). The results of TBARS and carbonyls indicated that NAEBT with pre-emulsification significantly alleviated oxidative damage to proteins (P < 0.05), resulting in an increased level of β-sheet (P < 0.05), as confirmed by FT-IR analysis. As a result, the water mobility of pork meat batter was restricted (P < 0.05), resulting in an increase in the energy storage modulus (P < 0.05) and a decrease in the pore size. In summary, the WHC of pork meat batter was improved by the antioxidant effect of the NAEBT. [ABSTRACT FROM AUTHOR]

To persist (without immigration) in habitats with unpredictable environmental conditions, annuals must produce seeds each year or have a seed bank. Thus, we predicted that compared to perennials, annuals have a wider germination temperature range (GTR, the difference in temperature between the week with the highest and the week with the lowest germination during the natural germination season). We determined the GTR via germination phenology data for 350 herbaceous species in 59 families from the eastern USA: summer annuals (SA), 63; winter annuals (WA), 83; monocarpic perennials (MP), 28; and polycarpic perennials (PP), 176. There was no significant phylogenetic signal for the GTR. The width of the GTR during the first spring germination season was 9.6, 8.7 and 8.8°C for MP, PP and SA, respectively, and during the first autumn germination season 12.8, 11.8 and 12.4°C for MP, PP and WA, respectively. Annuals did not have a wider GTR than perennials in either the spring or the autumn germination season. Our data suggest that selection for early germination in either spring or autumn has resulted in only small differences in the GTR. We predict that global warming will have little or no effect on reshaping the germination phenology of herbaceous species of temperate eastern North America. [ABSTRACT FROM AUTHOR]

The standard coal briquette specimens from Huaxing Mine, in Jilin, were made. The permeability test was performed in ZYS-1 equipment for the measurement of permeability to study the effects of confining stress, axial stress and temperature on permeability of coal briquette specimens. The results show that with the increasing confined stress, the permeability of coal briquette specimen decreases. The permeability of coal is greatly effected by differential stress. Under the condition of confined stress, with increasing differential stress (axial stress) the permeability of the specimen decreases due to the elastic contraction. When the specimen failed due to increasing differential stress their porosity volumes increase due to dilation, and the permeability also increases. Therefore the permeability of samples takes on "V" curve under low confined stress. However the permeability decreases under high confining stress. The flow of methane in coal is greatly effected by temperature. When the temperature increases, on one hand the kinematic viscosity of methane increases. On the other hand the grains of coal swell and lead to contraction of flow space and reduction of permeability. [ABSTRACT FROM AUTHOR]