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Among the current methods for lithium extraction from seawater, adsorption by manganese oxide ion sieves was considered to be the most promising one for industrial application. In this study, sol–gel, hydrothermal synthesis and two-stage heat treatment were used for preparing lithium ion sieve precursor Li 1.6 Mn 1.6 O 4 . Ion sieve MnO 2 ·0.5H 2 O was then obtained after eluting Li + from Li 1.6 Mn 1.6 O 4 by acid treatment. The crystal structure, surface morphology and adsorption properties of the ion sieve were characterized by XRD, SEM, HRTEM, adsorption isotherms and kinetics. Furthermore, the dynamic adsorption/desorption processes of granulated ion sieve were studied with concentrated seawater (saltern bittern) and HCl solution. The results showed that the ion sieve and its precursor were nearly pure spinel manganese oxides, and possessed one-dimensional nanowires morphologies. After granulation, the ion sieve exhibited good adsorption performance, and its adsorption process was in accordance with Lagergren Kinetics Equation and Langmuir Isotherm Equation. Under continuous and dynamic conditions, the ion-exchange capacity of this ion sieve for saltern bittern (pH = 10) was 10.05 mg/g, and after acid treatment, lithium-rich solution which was 30 times more concentrated than bittern (900 times than seawater) was obtained. The results implied that the ion sieve could be used for lithium extraction and enrichment in seawater system, and had a good application prospect.

Although there have been many studies on the runtime of evolutionary algorithms in discrete optimization, relatively few theoretical results have been proposed on continuous optimization, such as evolutionary programming (EP). This paper proposes an analysis of the runtime of two EP algorithms based on Gaussian and Cauchy mutations, using an absorbing Markov chain. Given a constant variation, we calculate the runtime upper bound of special Gaussian mutation EP and Cauchy mutation EP. Our analysis reveals that the upper bounds are impacted by individual number, problem dimension numbern, searching range, and the Lebesgue measure of the optimal neighborhood. Furthermore, we provide conditions whereby the average runtime of the considered EP can be no more than a polynomial ofn. The condition is that the Lebesgue measure of the optimal neighborhood is larger than a combinatorial calculation of an exponential and the given polynomial ofn.

Thin film nanocomposite (TFN) reverse osmosis (RO) membranes were prepared by incorporating hydrotalcite (HT) in polyamide layer during interfacial polymerization process using two methods: (1) dispersing HT in aqueous solution directly; (2) preparing layered double oxide (LDO) via calcination of HT and then dispersing the obtained LDO in aqueous solution to reconstruct HT. The results demonstrated that TFN RO membranes exhibited higher water flux compared with the pristine RO membrane, which could be mainly attributed to water channels constructed by HT as well as the enhancement of hydrophilicity and the increase of relative surface area. In addition, TFN RO membranes prepared using LDO showed higher water flux than those prepared using HT, which is contributed to the uniform distribution of water channels in polyamide layer resulting from the process of calcination and reconstruction reaction. Compared with pristine RO membrane, water flux of TFN RO membranes prepared with 0.075 wt% HT and those prepared with 0.050 wt% LDO was enhanced by 19.1% and 22.8% without sacrificing the salt rejection.

Satellite remote sensing technology has become one of the most effective methods for land surface monitoring in recent years, due to its advantages such as short period, large scale and rich information. Meanwhile, road extraction is an important field in the applications of high resolution remote sensing images. An intelligent and automatic road extraction algorithm with high precision has great significance for transportation, road network updating and urban planning. The fuzzy c-means (FCM) clustering segmentation algorithms have been used in road extraction, but the traditional algorithms did not consider spatial information. An improved fuzzy C-means clustering algorithm combined with spatial information (SFCM) is proposed in this paper, which is proved to be effective for noisy image segmentation. Firstly, the image is segmented using the SFCM. Secondly, the segmentation result is processed by mathematical morphology to remover the joint region. Thirdly, the road centerlines are extracted by morphology thinning and burr trimming. The average integrity of the centerline extraction algorithm is 97.98%, the average accuracy is 95.36% and the average quality is 93.59%. Experimental results show that the proposed method in this paper is effective for road centerline extraction.

Recently lower limit of detection (LOD) is necessary for rapid bacteria detection and analysis applications in clinical practices and daily life. A critical pre-conditioning step for these applications is bacterial concentration, especially for low level of pathogens. Sample volume can be largely reduced with an efficient pre-concentration process. Some approaches such as hollow-fiber ultra-filtration and electrokinetic technique have been applied to bacterial concentration. Since none of these methods can provide a concentrating method with a stable recovery efficiency, bacterial concentration still remains challenging Ceramic micro- filter can be used to concentrate the bacteria but the cross flow system keeps the bacteria in suspension. Similar harvesting bacteria using ultra-filtration showed an average recovery efficiency of 43% [1] and other studies achieved recovery rates greater than 50% [2]. In this study, an enhanced ceramic micro-filter with 0.14 μm pore size was proposed and demonstrated to optimize the concentration of E.coli. A high recovery rate (mean value >90%) and a high volumetric concentration ratio (>100) were achieved. Known quantities (104 to 106 CFU/ml) of E.coli cells were spiked to different amounts of phosphate buffered saline (0.1 to 1 L), and then concentrated to a final retentate of 5 ml to 10 ml. An average recovery efficiency of 95.3% with a standard deviation of 5.6% was achieved when the volumetric con- centration ratio was 10. No significant recovery rate loss was indicated when the volumetric concentration ratio reached up to 100. The effects of multiple parameters on E.coli recovery rate were also studied. The obtained results indicated that the optimized ceramic micro- filtration system can successfully concentrate E.coli cells in water with an average recovery rate of 90.8%.

Taking a large hydropower station as an example, the response spectrum based on scenario earthquake is determined. Firstly, the potential source of greatest contribution to the site is determined on the basis of the results of probabilistic seismic hazard analysis (PSHA). Secondly, the magnitude and epicentral distance of the scenario earthquake are calculated according to the main faults and historical earthquake of the potential seismic source zone. Finally, the response spectrum of scenario earthquake is calculated using the Next Generation Attenuation (NGA) relations. The response spectrum based on scenario earthquake method is less than the probability-consistent response spectrum obtained by PSHA method. The empirical analysis shows that the response spectrum of scenario earthquake considers the probability level and the structural factors, and combines the advantages of the deterministic and probabilistic seismic hazard analysis methods. It is easy for people to accept and provide basis for seismic...

An acceleration wavelet function, which is located in a time interval with finite length and does not have the problem of baseline drift, is constructed in this study. Utilizing the constructed wavelet as a corrective function, an iterative spectral matching method is proposed. The method superimposes the corrective wavelets onto any given initial ground‐motion acceleration to modify it to match the target response spectra with the required precision. This method not only avoids any additional baseline drift by virtue of the method of construction used for the corrective wavelet, but also can preserve the general nonstationary characteristics of the initial ground motion because of the localized nature of the corrective wavelet. Numerical examples demonstrate the capability of the proposed method in matching the target multidamping response spectra, especially in retaining the basic features of the original seed ground motions.

G protein–coupled receptor kinases (GRK) regulate diverse cellular functions ranging from metabolism to growth and locomotion. Here, we report an important contributory role for GRK5 in human prostate cancer. Inhibition of GRK5 kinase activity attenuated the migration and invasion of prostate cancer cells and, concordantly, increased cell attachment and focal adhesion formation. Mass spectrometric analysis of the phosphoproteome revealed the cytoskeletal-membrane attachment protein moesin as a putative GRK5 substrate. GRK5 regulated the subcellular distribution of moesin and colocalized with moesin at the cell periphery. We identified amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the expression of a T66-mutated moesin reduced cell spreading. In a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metastasis. Taken together, our results established GRK5 as a key contributor to the growth and metastasis of prostate cancer. Cancer Res; 74(13); 3489–500. ©2014 AACR.

Runtime analysis of continuous evolutionary algorithm (EA) is an open problem in theoretical foundation of evolutionary computation. There are fewer results about it than the runtime studies of discrete EA. For an example of (1+1)EA, an average gain model and its calculating method were proposed to produce a theory of runtime analysis as an index of computational time complexity. The average gain was computed to estimate the average runtime of two (1+1)EAs based on the mutation of standard normal distribution and uniform distribution, for Sphere function which is focused on by many researchers. The analysis result indicates that computational time complexity of the (1+1)EAs is exponential order. Furthermore, the solution speed of uniform-distribution mutation is faster than standard normal distribution with the same error accuracy and initial distance. Numerical results also verify the correctness of the proposed theory and the usefulness of the average gain model.

Androgen receptor (AR) is an androgen-activated transcription factor and drives prostate cancer (PCa) progression. Class I HDACs 1-3 are critical for activating AR-mediated transcription. Thus, targeting these HDACs is a promising strategy for treating PCa. Notably, along with significant adverse effects, several FDA-approved HDAC inhibitors broadly inhibiting different HDACs were ineffective for treating castration-resistant prostate cancer in clinical trials. Significantly, entinostat, an aminobenzamide analog specific to HDACs 1-3, extended overall survival for patients with breast cancer resistant to endocrine therapy. These observations suggest that HDACi selective to HDACs 1-3 may be effective for treating solid tumors including PCa. We have recently discovered the novel benzoylhydrazide class of HDAC inhibitors highly specific to HDACs 1-3. An optimized analog, SR-4370, exhibited low µM to nM potency against HDACs 1-3. SR-4370 markedly suppressed AR signaling, PCa cell proliferation in vitro, and prostate tumor growth in vivo. Gene expression profiling experiments revealed that SR-4370 downregulated AR, AR-Vs and AR target genes as well as the MYC oncogenic network. Chromatin accessibility assay using ATAC-seq showed that SR-4370 altered chromatin states in PCa cells. The chromatins with AR-binding sites became inaccessible on SR-4730 treatment, indicating that altered chromatin accessibility may contribute to the inhibition of AR signaling. Interestingly, SR-4370 sensitized C4-2 cells to enzalutamide. In PCa xenograft models, SR-4370 was effective to suppress tumor growth in vivo. Importantly, SR-4370 was well tolerated and did not cause observable adverse effects as judged by body weight and blood chemistry tests of treated mice. Our data suggest that SR-4370 may be a safe and clinically applicable treatment for advanced PCa refractory to current frontline treatments. (Supported by UFHealth Cancer Center, Florida Breast Cancer Foundation, James and Esther King Biomedical Research Program, and Bankhead-Coley Cancer Research Program, Florida Department of Health) Citation Format: Iqbal Mahmud, Guimei Tian, Jia Wang, Ryan Stowe, Zhiguang Huo, Yushan Zhang, Hamsa Thayek Purayil, Eric Helm, Theodore Drashansky, Dorina Avram, Yehia Daaka, William R. Roush, Daiqing Liao. SR-4370, a potent and selective inhibitor of class I HDACs, suppresses AR signaling and in vivo prostate tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4718.

Based on the analysis of water supply and water demand in Tianjin city, the early-warning index system of water resources was determined. Then, applying the relative principle of catastrophe theory, all kinds of the slope change-points of early-warning index curves, including the differences of water supply and water demand, water supply, water demand, increasing curve of population in Tianjin, total industrial output value and increasing curve of GDP are obtained by the rate analysis for slope change-point. So, the slope change-points model is established for early-warning system of water resources security in Tianjin City. After applying the theory of set pair analysis, which set a pair of “water-rich state (flood disaster)” and “water-shortage state (drought disaster)”, early-warning threshold and degree of water resources security are uniformly presented by the index of difference of water supply and demand. In this way, we could illustrate the early-warning degrees. Finally, according to the ...

Optofluidic devices combining micro-optical and microfluidic components bring a host of new advantages to conventional microfluidic devices. Aspects, such as optical beam shaping, can be integrated on-chip and provide high-sensitivity and built-in optical alignment. Optofluidic microflow cytometers have been demonstrated in applications, such as point-of-care diagnostics, cellular immunophenotyping, rare cell analysis, genomics and analytical chemistry. Flow control, light guiding and collecting, data collection and data analysis are the four main techniques attributed to the performance of the optofluidic microflow cytometer. Each of the four areas is discussed in detail to show the basic principles and recent developments. 3D microfabrication techniques are discussed in their use to make these novel microfluidic devices, and the integration of the whole system takes advantage of the miniaturization of each sub-system. The combination of these different techniques is a spur to the development of microflow cytometers, and results show the performance of many types of microflow cytometers developed recently.

In this paper, a synthesizing method based on the Hilbert transform is proposed to generate artificial earthquake ground‐motion samples, the nonstationary features of which are similar to those of given natural seismic recordings. With this aim in mind, the given natural seismogram, assumed to be a sample of some underlying random process, is first processed by the Hilbert transform to obtain its instantaneous amplitude and instantaneous phase functions. The instantaneous amplitude function is treated as an invariant variable for which the value will be preserved into the synthetic samples, whereas the instantaneous phase function is treated stochastically to address the randomness of the underlying ground‐motion process. By establishing the stochastic model for the instantaneous phase function, the underlying ground‐motion random process can be determined, and a series of its samples can be generated numerically. Synthetic examples demonstrate that the ground‐motion samples generated by the proposed method can maintain the general time‐variant features of original natural ground motions, and the method has application potential either in the engineering practice or in earthquake engineering research.

Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral GTP inactivator RGC2. The results support the idea that targeted interference of EP2/EP4 signal to RalA GTP may provide benefit to patients diagnosed with advanced kidney cancer.

Prognosis for patients with early stage kidney cancer has improved, but the treatment options for patients with locally advanced disease and metastasis remain few. Understanding the molecular mechanisms that regulate invasion and metastasis is critical for developing successful therapies to treat these patients. Proinflammatory prostaglandin E(2) plays an important role in cancer initiation and progression via activation of cognate EP receptors that belong to the superfamily of G protein-coupled receptors. Here we report that prostaglandin E(2) promotes renal cancer cell invasion through a signal transduction pathway that encompasses EP4 and small GTPase Rap. Inactivation of Rap signaling with Rap1GAP, like inhibition of EP4 signaling with ligand antagonist or knockdown with shRNA, reduces the kidney cancer cell invasion. Human kidney cells evidence increased EP4 and decreased Rap1GAP expression levels in the malignant compared with benign samples. These results support the idea that targeted inhibition of EP4 signaling and restoration of Rap1GAP expression constitute a new strategy to control kidney cancer progression.

Appropriate plant height is crucial for lodging resistance to improve the rice crop yield. The application of semi-dwarf 1 led to the green revolution in the 1960s, by predominantly increasing the rice yield. However, the frequent use of single sd1 gene sources may cause genetic vulnerability to pests and diseases. Identifying useful novel semi-dwarf genes is important for the genetic manipulation of plant architecture in practical rice breeding. In this study, introgression lines derived from two parents contrasting in plant height, Zhenshan 97 and Pokkali were employed to locate a gene with a large effect on plant height by the bulk segregant analysis method. A major gene, ph1, was mapped to a region closely linked to sd1 on chromosome 1; the additive effects of ph1 were more than 50 cm on the plant height and 2 days on the heading date in a BC(4)F(2) population and its progeny. ph1 was then fine mapped to BAC AP003227. Gene annotation indicated that LOC_OS01g65990 encoding a chitin-inducible gibberellin-responsive protein (CIGR), which belongs to the GRAS family, might be the right candidate gene of ph1. Co-segregation analysis of the candidate gene-derived marker finally confirmed its identity as the candidate gene. A higher expression level of the CIGR was detected in all the tested tissues in tall plants compared to those of short plants, especially in the young leaf sheath containing elongating tissues, which indicated its importance role in regulating plant height. ph1 showed a tremendous genetic effect on plant height, which is distinct from sd1 and could be a new resource for breeding semi-dwarf varieties.

Rice yield and heading date are two distinct traits controlled by quantitative trait loci (QTLs). The dissection of molecular mechanisms underlying rice yield traits is important for developing high-yielding rice varieties. Here, we report the cloning and characterization of Ghd8, a major QTL with pleiotropic effects on grain yield, heading date, and plant height. Two sets of near isogenic line populations were developed for the cloning of Ghd8. Ghd8 was narrowed down to a 20-kb region containing two putative genes, of which one encodes the OsHAP3 subunit of a CCAAT-box binding pro- tein (HAP complex); this gene was regarded as the Ghd8 candidate. A complementary test confirmed the identity and pleiotropic effects of the gene; interestingly, the genetic effect of Ghd8 was dependent on its genetic background. By regulating Ehd1, RFT1, and Hd3a, Ghd8 delayed flowering under long-day conditions, but promoted flowering under short-day conditions. Ghd8 up-regulated MOC1, a key gene controlling tillering and branching; this increased the number of tillers, primary and secondary branches, thus producing 50% more grains per plant. The ectopic expression of Ghd8 in Arabidopsis caused early flowering by 10 d—a situation similar to the one observed by its homolog AtHAP3b, when com- pared to wild-type under long-day conditions; these findings indicate the conserved function of Ghd8 and AtHAP3b in flowering in Arabidopsis. Our results demonstrated the important roles of Ghd8 in rice yield formation and flowering, as well as its opposite functions in flowering between rice and Arabidopsis under long-day conditions.

Both the heading date (HD) and the number of grains per panicle (GPP), which frequently correlate with each other, are important agronomic traits for rice. In this study, two sets of recombinant inbred lines (RILs) derived from crosses between Minghui 63 and Teqing (PMT) and Zhenshan 97 and Teqing (PZT), respectively, were used to dissect the genetic bases of the correlation between HD and GPP. GPP quantitative trait loci (QTLs) identified by conventional QTL analysis could be classified into two types, either dependent on or independent of HD regardless of the effect caused by flowering time. Conditional analysis detected only GPP QTLs independent of HD when the HD effect on GPP was eliminated. With conventional QTL analysis, eight and five GPP QTLs were detected in PZT and PMT, respectively. However, three and five QTLs were detected by conditional analysis. Five of eight were dependent on HD (type I QTLs) in PZT, and all QTLs identified in PMT were independent of HD (type II QTLs). Photoperiod response of qGPP7b near-isogenic lines confirmed that qGPP7b effects on GPP were caused by HD. The characteristics of type I and II QTLs related to their application in rice breeding are discussed.

With respect to the design ground motion of nuclear power plant (NPP), the Regular Guide 1.60 of the US not only defined the standard multi-damping response spectra, i.e. the RG1.60 spectra, but also definitely prescribed the peak ground displacement (PGD) value corresponding to the standard spectra. However, in the engineering practice of generating multi-damping-spectra-compatible artificial ground motion for the seismic design of NPP, the PGD value had been neglected. Addressing this issue, this paper proposed a synthesizing method which generates the artificial ground motion compatible with not only the target multi-damping response spectra but also the specified PGD value. Firstly, by the transfer formula between the power spectrum and the response spectrum, an initial uniformly modulated acceleration time history is synthesized by multiplying the stationary Gaussian process with the prescribed intensity envelope to simulate the amplitude-non-stationarity of earthquake ground motion. And then by superimposing a series of narrow-band time histories in the time domain, the initial time history is modified in the iterative manner to match the target PGD as well as the target multi-damping spectra with the pre-specified matching precisions. Numerical examples are provided to demonstrate the matching precisions of the proposed method to the target values.

To enhance understanding of the genetic basis of trait correlation in rice, a recombinant inbred line (RIL) population (F6 and F7) from a cross between Zhenshan97 and HR5 was employed to identify main quantitative trait loci (QTLs) and epistatic QTL (E-QTL). Highly significant positive correlations were detected among five traits of heading date (HD), plant height (PH), panicle length (PL), flag leaf length (FLL) and flag leaf width (FLW) in 2 environments. Four to 8 main QTLs were detected for an individual trait. No E-QTL was detected for PH. One, 4, 4 and 5 E-QTLs were detected for FLL, HD, FLW and PL, respectively. Each E-QTL individually explained less than 3% of trait variation except E-QFll1. Comparison of QTL results was made in order to dissect the genetic basis of trait correlation. We found that main QTLs with pleiotropic effects and QTL clusters were the main genetic basis of trait correlation. No E-QTL had pleiotropic effects. E-QTL played an important role in the genetic basis of individual trait, but it made a little contribution to trait correlation.

Background: Advanced prostate cancer is treated by androgen deprivation, but despite initial responses most tumors inevitably recur. The recurrent disease is termed castration-resistant prostate cancer (CRPC) and is characterized by active androgen receptor (AR) signaling despite decreased androgen levels. AR activity in CRPC occurs through a variety of mechanisms including upregulation of AR coactivators, such as Vav3, and expression of constitutively active AR variants, which lack the ligand binding domain and are linked to poor prognosis. We previously demonstrated that PC cells are growth inhibited by depletion of either Vav3 or the clinically prevalent AR variant, AR-V7 (1). Gene expression profiling in CRPC cells revealed that arginine vasopressin receptor 1a (AVPR1a) was significantly reduced by depletion of either Vav3 or AR-V7. AVPR1a is a G protein-coupled receptor that has not been previously linked to PC. Analysis of publicly available datasets showed that the AVPR1a gene exhibits a significant increase in copy number in human CRPC specimens and AVPR1a mRNA is upregulated in aggressive PC (2-4). Methods: To explore the role of AVPR1a in PC cells, we selectively depleted AVPR1a in a panel of prostate cancer and prostate epithelial cell lines and examined cell survival and proliferation in culture and soft agar, as well as cell migration and invasion. Conversely, we overexpressed AVPR1a in an androgen-dependent PC cell line, LNCaP, and examined growth in vitro and in vivo in androgen-depleted conditions. We investigated AVPR1a antagonism in two distinct in vivo models of CRPC progression and growth using an effective and safe-in-humans AVPR1a antagonist, relcovaptan. Results: We showed that depletion of AVPR1a greatly inhibited the proliferation of multiple CRPC cell lines but had less to no effect on androgen-dependent PC cells or nontumorigenic prostate epithelial cells. Depletion of AVPR1a also decreased CRPC cell anchorage-independent growth. Conversely, overexpression of AVPR1a in androgen-dependent LNCaP cells conferred castration resistance in vitro and in vivo. Similar to depletion of AVPR1a, treatment of PC cells with the AVPR1a antagonist relcovaptan decreased CRPC anchorage-independent growth. AVPR1a depletion or antagonism was also effective at decreasing CRPC metastatic properties: migration and invasion. In a preclinical xenograft model of progression to castration resistance, we found that relcovaptan halted tumor growth and stabilized circulating levels of a clinical tumor progression marker, prostate specific antigen (PSA). We evaluated relcovaptan efficacy on end-stage metastatic CRPC growth. C4-2B CRPC cells were injected into the tibias of castrated mice to model tumor growth and bone remodeling. Relcovaptan significantly inhibited tumor growth and prevented cancer cell-induced bone remodeling. Conclusion: AVPR1a is a promising new therapeutic target against CRPC. We propose that AVPR1a antagonists may be repurposed for PC therapy. References: 1. Peacock SO, et al. Mol Endocrinol 2012;12:1967-79. 2. Chandran UR, et al. BMC Cancer 2007;7:64. 3. Tamura K, et al. BMC Cancer 2007;67:5117-25. 4. Beltran H, et al. Nat Med 2016;22;298-305. Citation Format: Ning Zhao, Stephanie Peacock, Chen Hao Lo, Laine Heidman, Fiorella Magani, Meghan Rice, Ann Greene, Yushan Zhang, Yehia Daaka, Conor Lynch, Kerry Burnstein. Preclinical evaluation of an arginine vasopressin receptor 1A (AVPR1A) antagonist in castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A063.

Class I HDACs 1-3 are critical for the AR-mediated transcriptional program. Thus, targeting class I HDACs is a promising strategy for treating prostate cancer. However, several FDA-approved HDAC inhibitors (HDACi) broadly inhibiting different HDACs have been shown to be ineffective and overtly toxic for treating castration-resistant prostate cancer in clinical trials. These observations suggest that HDACi selective for class I HDACs may be more effective but less toxic for treating prostate cancer than pan HDACi. Notably, we and others have shown that HDACi of different chemical classes individually exhibit nonoverlapping but limited effects on the acetylome in cancer cells. We hypothesize that a combination treatment strategy with class I HDAC-selective HDACi of different chemical classes is more effective to block AR signaling and prostate tumor growth than such HDACi individually. We have recently discovered the novel benzoylhydrazide chemo-type of class I HDAC-selective HDACi with a unique pharmacologic profile. Medicinal chemistry effort led to an optimized analog, SR-4370, with 6 nM potency to HDAC3. In support of our hypothesis, SR-4370 in combination with the clinical class I HDACi entinostat markedly suppressed AR signaling, prostate cancer cell proliferation in vitro, and tumor growth in vivo, and the tumor-suppressive effects by the HDACi combination were more pronounced than by SR-4370 and entinostat individually. Gene expression profiling experiments revealed that the SR-4370/entinostat combination profoundly downregulated AR, AR-V7, and AR target genes, while activating immune and cell death signaling pathways. In a C4-2 xenograft model using athymic nude mice, the SR-4370/entinostat combination was highly effective in suppressing tumor growth. Importantly, these HDACi alone or in combination did not cause observable adverse effects judged by body weight and blood chemistry tests of treated mice. Overall, our data suggest that the SR-4370/entinostat combination may be a translatable treatment for castration-resistant prostate cancer. Citation Format: Guimei Tian, Iqbal Mahmud, Ryan Stowe, Yushan Zhang, Hamsa Thayek Purayil, William Roush, Yehia Daaka, Daiqing Liao. A combination of two chemically distinct inhibitors of class I HDACs is highly effective to suppress AR signaling and in vivo growth of prostate cancer xenograft [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B004.

Pd/Si-MFI membranes are fabricated by depositing palladium nanoparticles onto Si-MFI membranes via opposing reactants chemical fluid deposition in supercritical carbon dioxide. Palladium hexafluoroacetylacetonate [Pd(hfac)2] and ethanol are used as the Pd precursor and the reducing agent, respectively, in the deposition process. The resulting Pd/Si-MFI membrane is characterized using SEM, XRD, EPMA, TEM, and EDX techniques. It is demonstrated that a continuous layer of Pd particles with size of 10 nm is covered on the matrix surface while 30-nm Pd particles are plugged into the defects within the matrix. The H2/N2 permselectivity has been significantly increased due to the deposition of Pd nanoparticles in the Si-MFI membrane, which could keep stable below the critical temperature. This bifunctional membrane and similar membranes possess the application potential to achieve various one-step syntheses.

The ability to detect quantitative trait loci (QTLs) in a bi-allelic population is often limited. The power of QTL detection and identification of the most beneficial allele at each QTL could be greatly improved by comparing QTLs among different populations derived from connecting multi-parents. In this study, three sets of connected recombinant inbred lines (RILs) derived from the crosses between Zhenshan 97 and Minghui 63 (PZM), Zhenshan 97 and Teqing (PZT), and Minghui 63 and Teqing (PMT), respectively, were used. QTL analyses for the number of spikelets per panicle (SPP) and 1,000-grain weight (TGW) were performed in PZT, and five SPP QTLs on chromosomes 1, 6, and 7 and two TGW QTLs on chromosome 1 were detected. QTL for SPP was also identified in PMT, and six QTLs were detected on chromosomes 1, 2, 3, 6, and 7 in this population. In an earlier study, we identified five SPP QTLs and four TGW QTLs in PMT and nine TGW QTLs in PZM. Comparison of the QTL mapping results of these two studies showed that one QTL was common to the three populations, 11 QTLs were detected in two populations, and six QTLs were found in only one population. Comparison of genetic effect and the action direction of the QTLs detected in the three populations showed that additive effects of QTLs estimated in different populations were also expressed additively among three parental alleles. Additive effects of SPP7a estimated in three near-isogenic line F2 populations supported this finding. Based on these results, we suggest that pyramiding the most beneficial alleles among the three parents could efficiently improve rice yield.

By expressing the wave functions in the form of Fourier-Bessel series, the analytical solution for the two-dimension scattering problem of plane P waves by the cylindrical canyon topography that contains arbitrary number of circular-arc-shaped layers is presented firstly. And then, the convergence of the proposed series solution with the truncation number of terms is discussed, which demonstrates that the analytical solution can converge even for very high frequencies of the incident P wave. Finally, using this solution, the influences that are imposed on the stationary ground motion by the number and the sequence of alluvial layers, as well as the stiffness of soft interlayer contained in the canyon, are studied.

Angiogenesis is critical for cancer development and metastasis. Here we have employed a functional antibody library-based proteomic screen to identify proteins that participate in and might be used as therapeutic targets for tumor-related angiogenesis. Mice were immunized with human esophageal cancer endothelial cells (HECEC). The antibody library was established with the mouse spleen cells the serum of which had most anti-angiogenic effect. Monoclonal antibodies were subjected to an immunoreactive and functional screen and monoclonal antibodies that reacted strongly with cell surface antigens of HECECs and influenced their behavior were selected. Antigens that recognized by the antibodies were obtained by immunoprecipitation and then identified by mass spectrometry analysis. Migration-stimulating factor (MSF), the antigen of 1D2 antibody was identified using this approach. Further studies demonstrated that the 1D2 antibody suppressed MSF-effected migration and adhesion of HECECs on fibronectin matrix. Biodistribution assay showed that MSF targeting antibody 1D2 could specifically home to the xenograft with humanized blood vessel. Targeting treatment with 1D2 antibody significantly suppressed tumor growth through inhibition of human tumor-related angiogenesis. These results indicate that the functional antibody library-based proteomic screen can successfully identify proteins that involved in tumor-related angiogenesis and MSF may be a target for the anti-angiogenic treatment of the esophageal cancer.

The growth-correlated genes that are part of the neuroendocrine growth axis play crucial roles in the regulation of growth and development of pig. The identification of genetic polymorphisms in these genes will enable the scientist to evaluate the biological relevance of such polymorphisms and to gain a better understanding of quantitative traits like growth. In the present study, seven pairs of primers were designed to obtain unknown sequences of growth-correlated genes, and other 25 pairs of primers were designed to identify single nucleotide polymorphisms (SNP) using the denaturing high-performance liquid chromatography (DHPLC) technology in four pig breeds (Duroc, Landrace, Lantang and Wuzhishan), significantly differing in growth and development characteristics. A total of 101 polymorphisms were discovered in 10,707 base pairs (bp) from six genes of the ghrelin (GHRL), leptin (LEP), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and somatostatin (SS). The observed average distances between the SNP in the 5'UTR, coding regions, introns and 3'UTR were 134, 521, 81 and 92 bp, respectively. Four SNPs were found in the coding regions of IGF-II, IGFBP-2 and LEP, respectively. Two synonymous mutations were obtained in IGF-II and LEP genes respectively, and two non-synonymous were found in IGFBP-2 and LEP genes, respectively. Seven other mutations were also observed. Thirty-two PCR-RFLP markers were found among 101 polymorphisms of the six genes. The SNP discovered in this study would provide suitable markers for association studies of candidate genes with growth related traits in pig.

Methyl jasmonate (MeJA) is a potent promoter of plant senescence. ORESARA3 (ORE3)/ETHYLENE INSENSITIVE2 (EIN2), a protein similar to the members of the disease-related Nramp metal transporter family, is involved in cross-talk among several senescence processes related to abscisic acid, ethylene, MeJA, age and darkness. Nevertheless, the mechanism involved in the regulation of ORE3/EIN2 in exogenous MeJA-induced leaf senescence remains unclear. The C-terminal end of ORE3/EIN2 (CEND) was cleaved from ORE3/EIN2 located in the endoplasmic reticulum and then transferred to the nucleus during MeJA-induced senescence. Further analyses showed that mitogen-activated protein kinase 6 (MPK6) promoted CEND cleavage and nuclear translocation. Nuclear CEND accumulated ETHYLENE INSENSITIVE3 (EIN3), a transcription factor that accelerates MeJA-induced leaf senescence wherein ORESARA9 (ORE9) expression was suppressed in ein3, ore3, and mpk6 mutant plants. ChIP experiments revealed that EIN3 bound directly to the ORE9 promoter and this binding was enhanced in MeJA-induced leaf senescence. This study revealed the effect of the signalling pathway involving MPK6-ORE3-EIN3-ORE9 on regulating leaf senescence and provided insights into the mechanism of MeJA in promoting leaf senescence in Arabidopsis thaliana.

This article describes a hybrid simulation method to generate artificial ground motion time histories that are compatible with specified peak seismic acceleration, velocity and displacement as well as the target response spectrum of absolute acceleration. First, based on traditional methods that match the target spectrum in the frequency domain, an initial acceleration time history was synthesized to satisfy the specified peak acceleration, target spectral acceleration and intensity envelope. Second, by using the inversion formula of the seismic input to a linear single-degree-of-freedom system and by superimposing a series of narrow-band time histories in the time domain, the initial time history is further modified to allow its peak velocity and displacement to approach the targets and improve its matching precision with the target spectrum. Numerical examples are provided to demonstrate that the proposed method achieves good agreement with the target values.

Reconnaissance reports and pertinent research on seismic hazards show that liquefaction is one of the key sources of damage to geotechnical and structural engineering systems. Therefore, identifying site liquefaction conditions plays an important role in seismic hazard mitigation. One of the widely used approaches for detecting liquefaction is based on the time-frequency analysis of ground motion recordings, in which short-time Fourier transform is typically used. It is known that recordings at a site with liquefaction are the result of nonlinear responses of seismic waves propagating in the liquefied layers underneath the site. Moreover, Fourier transform is not effective in characterizing such dynamic features as time-dependent frequency of the recordings rooted in nonlinear responses. Therefore, the aforementioned approach may not be intrinsically effective in detecting liquefaction. An alternative to the Fourier-based approach is presented in this study, which proposes time-frequency analysis of earthquake ground motion recordings with the aid of the Hilbert-Huang transform (HHT), and offers justification for the HHT in addressing the liquefaction features shown in the recordings. The paper then defines the predominant instantaneous frequency (PIF) and introduces the PIF-related motion features to identify liquefaction conditions at a given site. Analysis of 29 recorded data sets at different site conditions shows that the proposed approach is effective in detecting site liquefaction in comparison with other methods.

In this paper, response spectral characteristics of one-, two-, and three-lobe sinusoidal acceleration pulses are investigated, and some of their basic properties are derived. Furthermore, the empirical mode decomposition (EMD) method is utilized as an adaptive filter to decompose the near-fault pulse-like ground motions, which were recorded during the September 20, 1999, Chi-Chi earthquake. These ground motions contain distinct velocity pulses, and were decomposed into high-frequency (HF) and low-frequency (LF) components, from which the corresponding HF acceleration pulse (if existing) and LF acceleration pulse could be easily identified and detected. Finally, the identified acceleration pulses are modeled by simplified sinusoidal approximations, whose dynamic behaviors are compared to those of the original acceleration pulses as well as to those of the original HF and LF acceleration components in the context of elastic response spectra. It was demonstrated that it is just the acceleration pulses contained in the near-fault pulse-like ground motion that fundamentally dominate the special impulsive dynamic behaviors of such motion in an engineering sense. The motion thus has a greater potential to cause severe damage than the far-field ground motions, i.e. they impose high base shear demands on engineering structures as well as placing very high deformation demands on long-period structures.

A systematic study on the influence of solution chemistry (pH, ionic strength) and bulk cell concentration on static and dynamic glutamicum adsorption onto polysulphone membrane, cell adsorption isotherms, and the rate of adsorption was performed. The interaction between cells and membrane surface in the absence of salt was dominated by electrostatic interaction due to the charges on the cell surface. The maximum adsorption occurred at isoelectric point (IEP) of cells, suggesting complementary electrostatically driven adsorption. At pH values below the IEP, adsorption increased as pH increased, but above the IEP, adsorption decreased as pH increased. Increased salt concentration reduces electrostatic repulsion between like-charged material (increasing adsorption) and decreases electrostatic attraction between oppositely charged material (decreased adsorption). Isotherms were performed to determine equilibrium adsorption behavior. Adsorption isotherms follow Langmuir laws, the parameters of which were determined. By taking into account electrostatic interactions, it has been possible to explain the evolution in the adsorption isotherms of the cell on the membrane surface with the solution chemical conditions. Rate of adsorption was determined by measuring adsorbed mass as a function of time at different pH values, ionic strength, and bulk feed concentration. In order to determine the effect of convective flow and electrostatic interactions on the cell adsorption behavior, static and dynamic adsorption were compared. Although convective forces tend to increase the amount of cell accumulated near the membrane surface, electrostatic interactions played a stronger role, as evident in the irreversible adsorption results for the static and dynamic cases. Controlling electrostatic interactions could reduce adsorption of cells onto the membrane, consequently reducing long-term membrane fouling.

Renal Cell Carcinoma (RCC) is one of the most lethal urological cancers worldwide, with incidence and mortality rates increasing in the past two decades. The disease does not present early clinical symptoms and is commonly diagnosed at the metastatic stage, leaving the 5-year survival rate at ≈ 10-20%. For a wide array of neoplasms, many key molecular determinants involved in mediating the process of tumor cell growth, invasion, and colonization at a secondary site (i.e. metastasis) have been reported. However, few molecular predictors have been identified for RCC, rendering the mechanism(s) underlying RCC metastases poorly understood. This results in the lack of effective treatment for patients with advanced RCC. G protein-coupled receptors (GPCRs) and their effectors, such as the arrestin proteins, have been implicated in tumor growth, metastasis, and angiogenesis. Arrestin proteins are well known for their function in the desensitization and trafficking of GPCRs, but have also been implicated in unique signaling pathways to regulate fundamental cellular functions, including cell cycle progression, cell migration, and survival. Furthermore, arrestin involvement has been identified in a number of breast, colorectal, lung, and hematological malignancies. However, the role of arrestin proteins in RCC is yet to be determined. Our preliminary data show that β-arrestin 2 (βarr2) protein levels correlate with growth and metastatic potential in several RCC cell lines, including ACHN and SN12C. We hypothesize that βarr2 regulates RCC tumor progression, specifically through involvement in proliferation, invasion, and metastatic processes. To test our hypothesis, we used genetic-based loss of function approaches such as interfering RNA and CRISPR/Cas9. βarr2 knockdown results indicated a role in RCC malignancy as it significantly reduces the migration and invasion of RCC cell lines in vitro. βarr2 knockout (KO) impaired 3D spheroid formation of these cells and induced morphological changes compared to control cells as observed under confocal microscopy imaging. Moreover, epithelial marker E-cadherin expression levels were elevated while mesenchymal markers twist1, twist2 and vimentin levels were decreased in the βarr2 KO cells compared to control, indicating a mesenchymal to epithelial transition. In vivo data support our hypothesis that βarr2 plays a critical role in tumor growth and metastasis. Our data suggests a role for βarr2 in RCC malignancy and present a possible target in development of therapies for patients with advanced RCC. Citation Format: Jude Masannat, Yushan Zhang, Hamsa Purayil, Iqbal Mahmud, Yehia Daaka. β-arrestin 2 mediates tumor growth and metastasis in renal cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1982. doi:10.1158/1538-7445.AM2017-1982

Androgen receptor (AR) has a pivotal role in the growth and survival of prostate cancer (PCa). Arrestin2 (Arr2) is a ubiquitous scaffolding/adaptor protein first characterized as a regulator of G protein-coupled receptor signaling. In this study, we report that Arr2 additionally functions as a positive regulator of AR expression and function in PCa cells. Expression level of Arr2 correlates with that of AR, and knockdown of Arr2 inhibits the expression of AR and its effectors prostate-specific antigen, transmembrane protease serine 2, FK506-binding protein 51 and fatty acid synthase. Mechanistically, the knockdown of Arr2 attenuates the binding of AR to androgen response elements and consequently decreases transcription of AR-regulated genes. The inhibition of AR by Arr2 knockdown occurs in both androgen-dependent and castration-resistant PCa (CRPC) cells, although the effect is more prominent in CRPC. Arr2 knockdown inhibits the in vitro CRPC cell proliferation, prostasphere growth and invasion, as well as the in vivo prostate tumor formation, local invasion and distant metastasis. These results illustrate a new role for Arr2 in the expression and activation of AR and its potential relevance as a target for therapeutic intervention and monitoring of disease progression.

Background. Current patient education and informed consent regarding weight loss expectations for bariatric surgery candidates are largely based on averages from large patient cohorts. The variation in weight loss outcomes illustrates the need for establishing more realistic weight loss goals for individual patients. This study was designed to develop a simple web-based tool which provides patient-specific weight loss expectations.Methods. Postoperative weight measurements after Roux-en-Y gastric bypass (RYGB) were collected and analyzed with patient characteristics known to influence weight loss outcomes. Quantile regression was used to create expected weight loss curves (25th, 50th, and 75th %tile) for the 24 months after RYGB. The resulting equations were validated and used to develop web-based tool for predicting weight loss outcomes.Results. Weight loss data from 2986 patients (2608 in the primary cohort and 378 in the validation cohort) were included. Preoperative body mass index (BMI) and age were found to have a high correlation with weight loss accomplishment (P<0.0001for each). An electronic tool was created that provides easy access to patient-specific, 24-month weight loss trajectories based on initial BMI and age.Conclusions. This validated, patient-centered electronic tool will assist patients and providers in patient teaching, informed consent, and postoperative weight loss management.

Human adipose tissue-derived stem cells (ADSCs) are an attractive multipotent stem cell source with therapeutic applicability across diverse fields for the repair and regeneration of acute and chronically damaged tissues. In recent years, there has been increasing interest in ADSC for tissue engineering applications. However, the mechanisms underlying the regulation of ADSC proliferation are not fully understood. Here we show that 47 transcripts are up-regulated while 23 are down-regulated in ADSC compared to terminally differentiated cells based on global mRNA profiling and microRNA profiling. Among the up-regulated genes, the expression of vascular endothelial growth factor (VEGF) is fine-tuned by miR-199a-5p. Further investigation indicates that VEGF accelerates ADSC proliferation whereas the multipotency of ADSC remains stable in terms of adipogenic, chondrogenic and osteogenic potentials after VEGF treatment, suggesting that VEGF may serve as an excellent supplement for accelerating ADSC proliferation during in vitro expansion.

General speaking, the heteroassociative morphological memory (HMM) is incomplete, namely, it cannot give a guarantee of perfect recall memory, even though without any input noises. The paper focuses on the problem and proposes a new method to improve performance of heteroassociative morphological memories. This method can realize the perfect recall of HMMs for perfect inputs or within a certain range of noises. An example is provided to illustrate the proposed method and its performance.

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic response is involved in human diseases, including cancer. Proinflammatory prostaglandin E2 (PGE2) is secreted by many cell types and plays important roles in the process of angiogenesis via activation of cognate EP1-4 receptors. Here, we provide evidence that PGE2 promotes the in vitro tube formation of human microvascular endothelial cells, ex vivo vessel outgrowth of aortic rings, and actual in vivo angiogenesis. Use of EP subtype-selective agonists and antagonists suggested EP4 mediates the prostaglandin-induced tube formation, and this conclusion was substantiated with small interfering RNA to specifically knockdown the EP4 expression. EP4 couples to Gαs, leading to activation of protein kinase A (PKA). Inhibition of PKA activity or knockdown of PKA catalytic subunit γ with RNAi attenuates the PGE2-induced tube formation. Further, knocking down the expression of Rap1A, HSPB6, or endothelial NO synthase, which serve as PKA-activatable substrates, inhibits the tube formation, whereas knockdown of RhoA or glycogen synthase kinase 3β that are inactivated after phosphorylation by PKA increases the tube formation. These results support the existence of EP4-to-PKA angiogenic signal and provide rationale for use of selective EP4 signal inhibitors as a probable strategy to control pathologic angiogenesis.

1National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China 2College of Biosafety Science and Technology Hunan Agricultural University, Changsha 410128, People’s Republic of China 3Present address: Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, People’s Republic of China

Background— Despite intensive investigation, how DNA methylation influences endothelial function remains poorly understood. We used methyl-CpG–binding domain protein 2 (MBD2), an interpreter for DNA methylome–encoded information, to dissect the impact of DNA methylation on endothelial function in both physiological and pathophysiological states. Methods and Results— Human umbilical vein endothelial cells under normal conditions express moderate levels of MBD2, but knockdown of MBD2 by siRNA significantly enhanced angiogenesis and provided protection against H 2 O 2 -induced apoptosis. Remarkably, Mbd2 −/− mice were protected against hind-limb ischemia evidenced by the significant improvement in perfusion recovery, along with increased capillary and arteriole formation. Loss of MBD2 activated endothelial survival and proangiogenic signals downstream of vascular endothelial growth factor signaling characterized by an increase in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor 2 expression, along with enhanced extracellular signal-regulated kinase 1/2 activation and BCL-2 expression. Mechanistic studies confirmed the methylation of CpG elements in the eNOS and vascular endothelial growth factor receptor 2 promoter. MBD2 binds to these methylated CpG elements and suppresses eNOS promoter activity. On ischemic insult, key endothelial genes such as eNOS and vascular endothelial growth factor receptor 2 undergo a DNA methylation turnover, and MBD2 interprets the changes of DNA methylation to suppress their expressions. Moreover, MBD2 modulation of eNOS expression is likely confined to endothelial cells because nonendothelial cells such as splenocytes fail to express eNOS after loss of MBD2. Conclusions— We provided direct evidence supporting that DNA methylation regulates endothelial function, which forms the molecular basis for understanding how environmental insults (epigenetic factor) affect the genome to modify disease susceptibility. Because MBD2 itself does not affect the methylation of DNA and is dispensable for normal physiology in mice, it could be a viable epigenetic target for modulating endothelial function in disease states.

Economic risk of project is the largest and most important risk. Along with carrying the Middle Route of the South-to-North Water Diversion Project into execution, how much water to transfer is a controversial problem. Synthetically considering the risk characteristic of the hydraulic engineering benefit for flood control, electricity generation, water supply, irrigation efficiency and annual cost, a model of economic risk analysis is established with the Principle Of Maximum Entropy (POME). It presents comprehensively contrastive analysis on the economic risk about 3 schemes (water transfer of 8.2×109 m3, 15×109 m3, 22×109 m3 respectively) for Middle Route of South-North Water Diversion Project, which will provide some references for the ascertaining of water-transfer volume and determining the base for more detailed risk analysis.

Background/Aims Bariatric surgery candidates often struggle when deciding between intensive lifestyle therapy, pharmacological therapy, and/or bariatric surgery for achieving their long-term weight loss (WL) goals. Moreover, they often have unrealistic WL expectations prior to surgery. Despite huge individual variation in surgically induced WL, patient education is currently based on average WL results derived from program experience or published literature. Improved patient education tools are needed to provide realistic individual expectations for surgical WL. The purpose of this study was to develop an electronic application for patient education that can aid in surgical decisions, establishing realistic WL goals, and monitoring WL success.