PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Nan Zhou - Top 30 Publications

Targeting the apoptotic Mcl-1-PUMA interface with a dual-acting compound.

Despite intensive efforts in the search for small molecules with anti-cancer activity, it remains challenging to achieve both high effectiveness and safety, since many agents lack the selectivity to only act on cancer cells. The interface of two apoptotic proteins, myeloid cell leukemia-1 (Mcl-1) and p53 upregulated modulator of apoptosis (PUMA), has been recently affirmed as a target for treating cancers, as the disruption of Mcl-1-PUMA binding can reduce cancer cell survival and protect normal cells from apoptosis. However, therapeutic agents that target this interface are yet to be found. In this work, we combined pharmacophore modelling and biological tests to seek small molecules which target the Mcl-1-PUMA interface. For the first time, a small-molecule compound was identified. Its dual activity has been validated to reduce PUMA-dependent apoptosis while deactivating Mcl-1-mediated anti-apoptosis in cancer cells. Our results would provide a new avenue for the development of effective and safe anti-cancer agents.

Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway.

Salidroside (Sal), the predominant component of a Chinese medicinal herb, Rhodiola rosea L., has become an attractive bioagent due to its significant anti-radiation, antioxidant and immune adjustment effects. We explored the radioprotective effect of Sal to ascertain whether it could enhance the anti-radiation effect of ON 01210.Na (Ex-RAD®) in vivo and in vitro, and elucidate its underlying mechanism. Our data demonstrated that Sal inhibited radiation-induced apoptosis, scavenged reactive oxygen species (ROS), and decreased the DNA damage of human umbilical vein endothelial cells (HUVECs). Sal downregulated the expression of Bax and p53 and increased the ratio of Bcl-2/Bax, which indicated that Sal inhibited the radiation-induced apoptosis through p53-dependent pathways. The radioprotection of the Sal pretreatment was also evidenced by an increasing survival rate of the mice, maintaining antioxidant enzyme levels in the liver, and accelerating hematopoietic recovery. The results suggest that Sal exhibits an excellent radioprotective effect with powerful antioxidant activity in vitro and in vivo. Sal enhanced the radioprotective effect of Ex-RAD by improving the antioxidant effect, the scavenging of ROS, by accelerating hematopoietic recovery and DNA repair as well as by regulating apoptotic and repair signaling pathways. Combined modality treatments were more effective than single-agent treatments, demonstrating the value of multiple-agent radioprotectants.

Sine wave gating silicon single-photon detectors for multiphoton entanglement experiments.

Silicon single-photon detectors (SPDs) are the key devices for detecting single photons in the visible wavelength range. Here we present high detection efficiency silicon SPDs dedicated to the generation of multiphoton entanglement based on the technique of high-frequency sine wave gating. The silicon single-photon avalanche diode components are acquired by disassembling 6 commercial single-photon counting modules (SPCMs). Using the new quenching electronics, the average detection efficiency of SPDs is increased from 68.6% to 73.1% at a wavelength of 785 nm. These sine wave gating SPDs are then applied in a four-photon entanglement experiment, and the four-fold coincidence count rate is increased by 30% without degrading its visibility compared with the original SPCMs.

Novel peptide MT23 for potent penetrating and selective targeting in mouse Melanoma cancer cells.

Cell-penetrating peptides (CPPs) have a great potential for intracellular delivery of cell-impermeable biological macromolecules in clinical therapy. However, their lack of cell and tissue specificity remains the primary limitation for their clinical development as drug delivery vehicles. In this study, based on phage display and an in silico approach, we found a novel CPP-MT23 with mouse melanoma cell specificity, it can only enter B16 melanoma cancer cells and without any cytotoxicity, Moreover, MT23 showed higher penetration efficiency based on fluorescence microcopy and quantitative assay, and it has capability for mediating functional Apoptin into cells in vitro or in vivo. Moreover, MT23-Apoptin can significantly inhibit tumor growth and induce the cell apoptosis in B16 tumor bearing mice. To sum up, all the results implicated that MT23 has the potential to deliver exogenous therapeutic proteins for further use and it also expected to lay the foundation for developing human melanoma cancer cell specific CPP.

Urachal mucinous adenocarcinoma with pseudomyxoma peritonei: A case report.

Pseudomyxoma peritonei is an unusual clinical condition, and the appendix and ovaries are reported as the primary sites.

Transcrestal sinus floor augmentation with immediate implant placement applied in three types of fresh extraction sockets: A clinical prospective study with 1-year follow-up.

Immediate implant insertion and transcrestal sinus augmentation both can provide a lot of advantages for patients and clinicians.

Effects of postnatal overfeeding and fish oil diet on energy expenditure in rats.

Early life nutrition may have a role in the regulation of metabolism in adulthood. The present study aimed to evaluate the effects of postnatal overfeeding and a postweaning fish oil diet on energy expenditure.

A Novel Partial Discharge Localization Method in Substation Based on a Wireless UHF Sensor Array.

Effective Partial Discharge (PD) localization can detect the insulation problems of the power equipment in a substation and improve the reliability of power systems. Typical Ultra-High Frequency (UHF) PD localization methods are mainly based on time difference information, which need a high sampling rate system. This paper proposes a novel PD localization method based on a received signal strength indicator (RSSI) fingerprint to quickly locate the power equipment with potential insulation defects. The proposed method consists of two stages. In the offline stage, the RSSI fingerprint data of the detection area is measured by a wireless UHF sensor array and processed by a clustering algorithm to reduce the PD interference and abnormal RSSI values. In the online stage, when PD happens, the RSSI fingerprint of PD is measured via the input of pattern recognition for PD localization. To achieve an accurate localization, the pattern recognition process is divided into two steps: a preliminary localization is implemented by cluster recognition to reduce the localization region, and the compressed sensing algorithm is used for accurate PD localization. A field test in a substation indicates that the mean localization error of the proposed method is 1.25 m, and 89.6% localization errors are less than 3 m.

Adolescents' Responses to Marital Conflict: The Role of Cooperative Marital Conflict.

Not all youth exposed to hostile marital interactions develop negative responses to marital conflict. Cooperative marital conflict has long been considered as an important way of managing conflict and may serve as an important context in which hostility might convey during marital interactions. In light of little prior attention placed on the positive side of conflict processes, the main and moderating effects of cooperative marital conflict on youth responses to marital conflict were examined in a sample of 416 2-parent families using a multimethod, 2-year prospective design. Cooperative marital conflict was associated with decreases in youth emotional dysregulation, perceived threat, and behavioral dysregulation, and increases in constructive family representations and coping efficacy. As a specific dimension of cooperation, effective conflict resolution was associated uniquely with elevated youth coping efficacy, and decreased emotional and behavioral dysregulation; marital warmth was associated uniquely with increased constructive family representations. Significant interactions between marital hostility and marital cooperation also were found. These findings highlight the importance of examining cooperation above and beyond hostility in studies of marital conflict in order to better understand youth development during early adolescence. (PsycINFO Database Record

Discovery of a tetrahydroisoquinoline-based HDAC inhibitor with improved plasma stability.

Histone deacetylase inhibitors with desirable pharmacokinetic profiles which can be delivered to solid tumor tissues in large amount might be promising to treat solid tumor effectively. Herein, structural modification of a previously reported tetrahydroisoquinoline-based HDAC inhibitor 1 was carried out to improve its plasma stability for more feasible drug delivery. Among three newly synthesized analogs, the in vitro rat plasma stability of compound 2 (t1/2=630min) was over 5-fold improved than its parent 1 (t1/2=103min). In vitro activity evaluation showed that compound 2 and 1 exhibited similar HDACs inhibitory activity, which was validated by western blot analysis and antiproliferative assay. Moreover, compared with 1, compound 2 exhibited comparable, if not higher, in vivo antitumor activity in a human breast carcinoma (MDA-MB-231) xenograft model.

Added Value of Parotid R2* Values for Evaluation of Sjögren Syndrome: A Preliminary Study.

To explore the application of parotid R2* values for evaluating Sjögren syndrome (SS).

Compact tunable photonic comb filter on a silicon platform.

We propose and demonstrate a compact wavelength- and bandwidth-tunable photonic comb filter on a silicon platform. It is a Fabry-Perot (FP) cavity fabricated on silicon-on-insulator, which is composed of two cascaded Sagnac loop mirrors (SLMs) with multimode-interferometer-assisted Mach-Zehnder interferometer (MZI) couplers. The effective length of the FP cavity and the reflectivity of the SLMs can be dynamically changed based on thermal-optical effects by tuning three phase shifters along the cavity length and MZI arms, leading to center wavelength tuning and bandwidth tuning of the comb filter. Three tuning cases are investigated. By independently or simultaneously tuning three microheaters, center wavelength tuning with a tuning efficiency of ∼0.017  nm/mW and bandwidth tuning from 4.37 to 27.6 GHz are achieved in the experiment.

Course constructions: A case-base of forensic toxicology.

Forensic toxicology education in China is limited by insufficient teaching methods and resources, resulting in students with adequate theoretical principles but lacking practice experience. Typical cases used as teaching materials vividly represent intoxication and provide students with an opportunity to practice and hone resolving skills. In 2013, the Department of Forensic Pathology at Zhongshan School of Medicine began to construct top-quality courses in forensic toxicology, with its first step, creating a base containing typical cases of intoxication. This essay reviews the construction process of said cases-base, which is intended to set an example of forensic toxicology education.

Eg5 Overexpression Is Predictive of Poor Prognosis in Hepatocellular Carcinoma Patients.

Eg5 (kinesin spindle protein) plays an essential role in mitosis. Inhibition of Eg5 function results in cell cycle arrest at mitosis, which leads to cell death. To date, Eg5 expression and its prognostic significance have not been studied in hepatocellular carcinoma (HCC). In this study, 26 freshly frozen HCC tissue samples and matched peritumoral tissue samples were evaluated with a one-step qPCR test and immunohistochemical (IHC) analysis was conducted on 156 HCC samples to investigate the relationships among Eg5 expression, clinicopathological factors, and prognosis. Eg5 mRNA and protein expression levels were significantly higher in HCC tissues relative to matched noncancerous tissues (p < 0.05). High Eg5 protein expression was significantly related to liver cirrhosis (p = 0.038) and TNM stage (p = 0.008). Kaplan-Meier survival and Cox regression analyses revealed that Eg5 overexpression (p = 0.001), liver cirrhosis (p = 0.009), and TNM stage (p = 0.025) were independent prognostic factors for overall survival. These findings indicate that Eg5 expression can be used as a biomarker of poor prognosis and as a novel therapeutic target for HCC.

Bio-oil from fast pyrolysis of lignin: Effects of process and upgrading parameters.

Effects of process parameters on the yield and chemical profile of bio-oil from fast pyrolysis of lignin and the processes for lignin-derived bio-oil upgrading were reviewed. Various process parameters including pyrolysis temperature, reactor types, lignin characteristics, residence time, and feeding rate were discussed and the optimal parameter conditions for improved bio-oil yield and quality were concluded. In terms of lignin-derived bio-oil upgrading, three routes including pretreatment of lignin, catalytic upgrading, and co-pyrolysis of hydrogen-rich materials have been investigated. Zeolite cracking and hydrodeoxygenation (HDO) treatment are two main methods for catalytic upgrading of lignin-derived bio-oil. Factors affecting zeolite activity and the main zeolite catalytic mechanisms for lignin conversion were analyzed. Noble metal-based catalysts and metal sulfide catalysts are normally used as the HDO catalysts and the conversion mechanisms associated with a series of reactions have been proposed.

Changes in 11β-Hydroxysteroid Dehydrogenase and Glucocorticoid Receptor Expression in Kawasaki Disease.

This study aims to investigate the significance of changes in the expression 11β-hydroxysteroid dehydrogenase (11β-HSD) and glucocorticoid receptor (GR) for the development of Kawasaki disease (KD).

Retinoid acid-induced microRNA-31-5p suppresses myogenic proliferation and differentiation by targeting CamkIIδ.

We previously reported that Wnt5a/CaMKIIδ (calcium/calmodulin-dependent protein kinase II delta) pathway was involved in the embryonic tongue deformity induced by excess retinoic acid (RA). Our latest study found that the expression of miR-31-5p, which was predicted to target the 3'UTR of CamkIIδ, was raised in the RA-treated embryonic tongue. Thus, we hypothesized that the excess RA regulated Wnt5a/CaMKIIδ pathway through miR-31-5p in embryonic tongue.

Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study.

Early evaluation of radiation-induced parotid damage with diffusion kurtosis imaging: a preliminary study.

Background Radiation-induced parotid gland damage is a common complication of radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC), which always causes xerostomia, dysphagia, dental caries, and even sleep disorders. Early evaluation of radiation-induced parotid damage is required to facilitate early interventions. Purpose To early-evaluate radiation-induced parotid damage using diffusion kurtosis imaging (DKI) in patients with NPC undergoing RT. Material and Methods Thirty-two patients with NPC underwent DKI for parotid glands pre-RT (two weeks before RT), mid-RT (five weeks after RT began), and post-RT (four weeks after RT). Parotid volume, apparent diffusion coefficient (ADC), corrected diffusion coefficient (D), excess diffusion kurtosis coefficient (K) values, mean radiation dose, and xerostomia degrees were recorded and analyzed. Results During RT, parotid ADC (change rates = 41.3 ± 25.2% at mid-RT, 70.8 ± 34.3% at post-RT) and D (change rates = 41.9 ± 25.2% at mid-RT, 63.2 ± 30.2% at post-RT) increased, while parotid volume (atrophy rates = 31.5 ± 7.9% at mid-RT, 30.6 ± 10.3% at post-RT) and K (change rates = -17.8 ± 11.0% at mid-RT, -29.8 ± 9.0% at post-RT) decreased significantly (all P < 0.001). At post-RT, the change rate of parotid D values was significantly positively correlated with the mean radiation dose ( r = 0.455, P < 0.001). Parotid ADC, D, and K values showed excellent intra- and inter-observer agreement (intraclass correlation coefficient = 0.946-0.985). Conclusion Radiation-induced parotid damage in patients with NPC undergoing RT could be effectively evaluated by DKI in the early stage.

Family and Individual Risk and Protective Factors of Depression among Chinese Migrant Children with Oppositional Defiant Disorder Symptoms.

Migrant children reached 35.81 million in China and were vulnerable to serious emotional problems including depression. The present study aimed to identify the family and individual risk and protective factors for depression in an at-risk sample of Chinese migrant children. Participants were 368 children (9.47 ± 1.46 years old, 73.4% boys) who had at least one symptom of Oppositional Defiant Disorder symptoms (ODD) and their parents in Mainland China. Risk and protective factors within both family (i.e., family maltreatment and family functioning) and individual (i.e., automatic thoughts and resilience) perspectives. Family maltreatment and negative automatic thoughts served as risk factors in relation to children's depression. Further, automatic thoughts mediated the relationship between family maltreatment and children's depression. Family functioning (cohesion, but bot adaptability) and individual resilience could buffer the effects of risk factors in the Structure Emotion Model such that both cohesion and resilience moderated the relationship between family maltreatment and children's automatic thoughts only. Our findings highlighted the urgent need to decrease risk factors and increase protective factors of both family and child individual characteristics in prevention and intervention depression among migrant children with ODD symptoms in China.

Enhanced Phototoxicity of Photodynamic Treatment by Cx26-composed GJIC via ROS-, calcium- and lipid peroxide-mediated pathways.

In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26-composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of "death signal", thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26-composed GJ formation at high density enhances the phototoxicity of Photofrin-PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high-density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC-mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide-mediated stress signaling pathways. The work presents the ability of Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26-formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture: The survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed) and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density condition.

Two-band and pauli-limiting effects on the upper critical field of 112-type iron pnictide superconductors.

The temperature dependence of upper critical field μ0Hc2 of Ca0.83La0.17FeAs2 and Ca0.8La0.2Fe0.98Co0.02As2 single crystals are investigated by measuring the resistivity for the inter-plane (H//c) and in-plane (H//ab) directions in magnetic fields up to 60 T. It is found that μ0Hc2(T) of both crystals for H//c presents a sublinear temperature dependence with decreasing temperature, whereas the curve of μ0Hc2(T) for H//ab has a convex curvature and gradually tends to saturate at low temperatures. μ0Hc2(T) in both crystals deviates from the conventional Werthamer-Helfand-Hohenberg (WHH) theoretical model without considering spin paramagnetic effect for H//c and H//ab directions. Detailed analyses show that the behavior of μ0Hc2(T) in 112-type Iron-based superconductors (IBSs) is similar to that of most IBSs. Two-band model is required to fully reproduce the behavior of μ0Hc2(T) for H//c, while the effect of spin paramagnetic effect is responsible for the behavior of μ0Hc2(T) for H//ab.

Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients.

Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Of these, 3 accompanied by pulmonary arterial hypertension (PAH), 1 accompanied by hypertension, and 2 accompanied by renal thrombotic microangiopathy (TMA), which was confirmed by renal biopsy. This confirms combined MMA and homocysteinemia should be considered in the differential diagnosis of DLD with or without PAH or renal TMA.

Diffusional kurtosis imaging of parotid glands in Sjögren's syndrome: Initial findings.

To explore the role of diffusion kurtosis imaging (DKI) of parotid glands in diagnosing Sjögren's syndrome (SS).

Marital Well-Being and Depression in Chinese Marriage: Going Beyond Satisfaction and Ruling Out Critical Confounders.

Based on data obtained from 203 Chinese couples during the early years of marriage and utilizing the actor-partner interdependence model, this study examined the prospective associations between different aspects of marital well-being (i.e., marital satisfaction, instability, commitment, and closeness) and depressive symptoms (assessed 2 years later) while controlling for critical intrapersonal (i.e., neuroticism and self-esteem) and contextual (i.e., stressful life events) confounders. Results indicated that (a) when considering different aspects of marital well-being as predictors of depressive symptoms separately, each aspect was significantly associated with spouses' own subsequent depressive symptoms; (b) when examining various aspects of marital well-being simultaneously, only husbands' commitment, husbands' instability, and wives' instability were significantly associated with their own subsequent depressive symptoms above and beyond the other aspects; and (c) the associations between husbands' commitment, husbands' instability, and wives' instability and their own subsequent depressive symptoms remained significant even after controlling for potential major intrapersonal and contextual confounders. Such findings (a) provide evidence that the marital discord model of depression may apply to Chinese couples, (b) highlight the importance of going beyond marital (dis)satisfaction when examining the association between marital well-being and depression, and (c) demonstrate that marital well-being can account for unique variance in depressive symptoms above and beyond an array of intrapersonal and contextual risk factors. (PsycINFO Database Record

The mechanism of force transference in feet of children ages two to six.

The aim of this study was to design an algorithm to quantify the plantar force transference of children from ages 2-6. In total, 319 healthy children without abnormal gait patterns, foot deformities or injuries, able to walk independently, and with normal BMIs were recruited, and their plantar force distributions were measured. Their plantar areas were divided into ten parts: the hallux, toes #2-5, the first to fifth metatarsal heads (1st-5th MTH), the mid-foot (MF), medial heel (MH) and lateral heel (LH), in which a relative force-time integral (FTIrel) (%) was calculated. Our results show that the FTIrel was significantly transferred along either the transverse or longitudinal arches. The middle of the forefoot and the toe areas were the two main loading regions in children aged 2-3, and posterior to anterior FTIrel shifting was typical. However, anterior to posterior and lateral to medial FTI transferences were found in children aged 5-6, and major loading was found in the heel area. Further, loading in the mid-foot varied with the child's development and was observed to tend to decrease over time. Overall, according to the algorithm designed in this study, these results demonstrated that the development of the arches, both in transverse and longitudinal directions, had already begun in early stages of toddlerhood. Meanwhile, the arches were an important attractor engaged in the windlass mechanism while walking, and they played a major role as bridges to promote posterior to anterior and medial to lateral force transference.

Biochars with excellent Pb(II) adsorption property produced from fresh and dehydrated banana peels via hydrothermal carbonization.

Fresh and dehydrated banana peels were used as biomass feedstock to produce highly effective sorbent biochars through a facile one-step hydrothermal carbonization approach with 20%vol phosphoric acid as the reaction medium. The elemental ratio of oxygen content of the two as-prepared biochars were about 20%, and the FT-IR analysis confirmed the existence of abundant surface functional groups such as hydroxyl and carboxyl which greatly enhanced the adsorption performance. The sorbents showed excellent lead clarification capability of 359mg·g(-1) and 193mg·g(-1) for dehydrated and fresh banana peels based biochars, respectively. The change of the CO/OCO and the appearance of PbO/PbOC on the surface after adsorption confirmed that the ion exchange might be the dominant mechanism. The dehydration and pulverization pre-treatment and the addition of phosphoric acid can benefit the formation of those functional groups and hydrothermal carbonization can be a promising method to transfer biomass like fruit peels into biochars with excellent adsorption performance.

Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro.

The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD-POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes.

Effects of feedstock characteristics on microwave-assisted pyrolysis - A review.

Microwave-assisted pyrolysis is an important approach to obtain bio-oil from biomass. Similar to conventional electrical heating pyrolysis, microwave-assisted pyrolysis is significantly affected by feedstock characteristics. However, microwave heating has its unique features which strongly depend on the physical and chemical properties of biomass feedstock. In this review, the relationships among heating, bio-oil yield, and feedstock particle size, moisture content, inorganics, and organics in microwave-assisted pyrolysis are discussed and compared with those in conventional electrical heating pyrolysis. The quantitative analysis of data reported in the literature showed a strong contrast between the conventional processes and microwave based processes. Microwave-assisted pyrolysis is a relatively new process with limited research compared with conventional electrical heating pyrolysis. The lack of understanding of some observed results warrant more and in-depth fundamental research.

Functional MRI of human pancreas using BOLD contrast: Responses following glucose ingestion.

To evaluate the response of the pancreas to glucose ingestion in healthy volunteers by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI).