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We present a super sub-Nyquist Hadamard single-pixel terahertz (THz) imaging system in which the THz waves are modulated by a digital micromirror device and a laser driver. Spatial coding of the THz radiation is performed using the cake-cutting (CC)-order Hadamard basis. THz images are reconstructed from a series of coding sequences of the measurement intensity. We prove that with the use of super sub-Nyquist sampling, single-pixel THz imaging with 87% fidelity and a signal-to-noise ratio of more than 23 dB can be achieved using 10% of the CC-order Hadamard basis patterns. The total variation regularization algorithm is shown to have higher robustness to noise than the Hadamard transform and thus offers a good technical solution for single-pixel THz imaging. [ABSTRACT FROM AUTHOR]

Livestock grazing exclusion is the most widely used grassland restoration strategy. However, the impacts of long-term grazing exclusion remain unknown. To clarify the impacts of long-term grazing exclusion on plant and soil features, we examined the plant biomass, plant diversity, and the physical, chemical, and enzymatic soil properties of an area with a history of 40 years of grazing exclusion within the Xinlin Gol grassland of China. Our results showed that grazing exclusion increased the plant diversity and biomass effectively, especially the gramineous, forb, and shrub biomass and the forb and shrub diversity. In addition, grazing exclusion reduced the bulk density of the soil, increased its water content, amount of organic matter, and available nitrogen content, and slowed down the decreasing trend in the amount of total nitrogen with the increase in soil depth. Plant biomass and litter mass was identified as important to connecting plant features and soil nutrient content. In particular, shrub biomass and diversity characteristics were positively correlated with each other, and had the closest coupling with soil properties among all plant functional groups. After considering the results, we concluded that grazing exclusion can be effective in restoring a natural grassland environment. [ABSTRACT FROM AUTHOR]

A novel isochronous mass spectrometry, termed as B ρ -defined IMS, has been established at the experimental cooler-storage ring CSRe in Lanzhou. Its potential has been studied through high precision mass measurements of 58 Ni projectile fragments. Two time-of-flight detectors were installed in one of the straight sections of CSRe, thus enabling simultaneous measurements of the velocity and the revolution time of each stored short-lived ion. This allows for calculating the magnetic rigidity B ρ and the orbit length C of each ion. The accurate B ρ (C) function has been constructed, which is a universal calibration curve used to deduce the masses of the stored nuclides. The sensitivity to single stored ions, fast measurement time, and background-free characteristics of the method are ideally suited to address nuclides with very short lifetimes and smallest production yields. In the limiting case of just a single particle, the achieved mass resolving power allows one to determine its mass-over-charge ratio m/q with a remarkable precision of merely ∼ 5 keV. Masses of T z = - 3 / 2 fp-shell nuclides are re-determined with high accuracy, and the validity of the isospin multiplet mass equation is tested up to the heaviest isospin quartet with A = 55 . The new masses are also used to investigate the mirror symmetry of empirical residual proton-neutron interactions. [ABSTRACT FROM AUTHOR]

Large-scale landslides along rivers that incised valleys in the mountain region have been widely concerned. Occurrences of landslides along rivers are closely linked with river valley evolution. Field investigations and numerical approaches were employed to examine the landslide formation mechanism and analyze the relationship between landslide and river valley slope evolution. The formation mechanism of the multi-level landslide is investigated. The results indicate that gentle weak structural planes parallel to the slope were the geological origins of the landslide. The causes of the landslide are regional tectonics, river valley cutting, and water infiltration. River valley cutting causes the unloading of the weak bedding structure of the slopes, which pulls the intermediate strata out like a drawer. The interbedded weak interlayer is a determinant factor for formation of the landslide, and engineering excavation and continuous rainfall further induced the landslide. [ABSTRACT FROM AUTHOR]

We propose an effective approach for determining the manufacturer of oxytetracycline based on terahertz time-domain spectroscopy and chemometrics. The applied method allowed detection and distinction of oxytetracycline tablets produced by four Chinese manufacturers. Absorption spectra within the frequency range of 0.2–1.6 THz were acquired for analysis, and principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) were implemented for dimensionality reduction. The obtained data were input into different classifiers, namely, grid-search support vector machines (SVM), genetic algorithm-SVM, particle swarm optimizations (PSO–SVM), decision trees, and random forests. The results indicated that the absorption spectra of oxytetracycline produced by the four manufacturers could be differentiated, and that t-SNE outperformed PCA in terms of dimensionality reduction. The optimal classifier was obtained by combining t-SNE and PSO–SVM, and this approach demonstrated the highest cross validation accuracy (98.33%), an average training set accuracy of 97.72%, and an average test set accuracy of 94.25%. The novel approach described herein achieved rapid classification of oxytetracycline and allowed accurate tracing of the manufacturers. [ABSTRACT FROM AUTHOR]

Quinazolinones and their derivatives are an important class of broad-spectrum pharmacodynamic groups with a wide range of pharmacological activities. We designed and synthesized the new 4-(2-chlorobenzyl)imidazole[1,2-a]quinazolin-5(4H)-one compound and used 1H and 13C NMR, FTIR spectroscopy and MS to determine its structure. In addition, the structure of the single crystal is confirmed using X-ray diffraction. The optimal structure of the compound is calculated by DFT using the B3LYP functional group (based on 6-311G(2d,p)) and compared with the structure determined by X-ray diffraction. The results show that the crystal structure determined by X-ray diffraction is consistent with the molecular structure optimized using DFT. [ABSTRACT FROM AUTHOR]

Sulfonamides are used as antibacterial drugs for decades. 3-bromo-N-(3-fluorophenyl) benzenesulfonamide is synthesized by the amidation reaction. The structure of the title compound is confirmed by FTIR, 1H and 13C NMR, and MS spectroscopies. At the same time, the single crystal of the compound is analyzed by X-ray diffraction and the conformational analysis is performed. Density functional theory (DFT) is used to further calculate the molecular structure, and the results are consistent with the X-ray diffraction results. In addition, DFT is also used to calculate and analyze the electrostatic potential and the frontier molecular orbital of the molecule, which provides some references for the analysis of the physical and chemical properties of the molecule. In addition, vibrational frequencies are analyzed, revealing some physicochemical properties of the title compound. [ABSTRACT FROM AUTHOR]

Summary: This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type. Introduction: Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis. Methods: Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD. Results: For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (β = − 1.116 (95% confidence interval, 95%CI: − 2.210, − 0.023), P = 0.045); vigorous PA showed a direct effect (β = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently. Conclusions: Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD. [ABSTRACT FROM AUTHOR]

Summary: Both sarcopenia and low bone mineral density (BMD) have become public health concerns. We found that presarcopenic and/or sarcopenic individuals were more likely to have lower BMD. And this relationship has race and sex-specific discrepancy. Purpose: The purpose of the study was to investigate the racial and gender differences in the relationship between sarcopenia and BMD among older adults. Methods: Totally, 5476 subjects (mean age = 65.7 ± 6.4) of non-Hispanic White (n = 3297), non-Hispanic Black (n = 1265), and non-Hispanic Asian (n = 914) were analyzed. Sarcopenia was defined according to the revised European consensus on definition and diagnosis of sarcopenia (EWGSOP2). General linear model and multivariable linear regression model were used to examine the relationship between sarcopenia and regional/whole body BMD stratified by race and sex. Adjustments were conducted for physiological, behavioral, and disease factors. Results: Comparing with normal older participants, presarcopenic and sarcopenic elderly were more likely to have lower BMD. Although the difference was not statistically significant in a few sub-groups, among the three racial groups, the strongest association between sarcopenia and BMD was found in non-Hispanic Black people, followed by non-Hispanic White people and non-Hispanic Asian people. In addition, significant differences of BMD across sarcopenia stages were found in more sub-groups in women than in men after adjusting for covariates. Conclusions: In this older cohort, sarcopenia is significantly related to low regional/whole-body BMD, and these associations vary by race and sex. Consideration in race and sex is warranted when developing strategies to maintain or minimize BMD loss. [ABSTRACT FROM AUTHOR]

Summary: By adopting the extension approaches of Mendelian randomization, we successfully detected and prioritized the potential causal risk factors for BMD traits, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases. Introduction: Osteoporosis (OP) is a common metabolic skeletal disease characterized by reduced bone mineral density (BMD). The identified SNPs for BMD can only explain approximately 10% of the variability, and very few causal factors have been identified so far. Methods: The Mendelian randomization (MR) approach enables us to assess the potential causal effect of a risk factor on the outcome by using genetic IVs. By using extension methods of MR—multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA)—we intend to estimate the causal relationship between fifteen metabolic risk factors for BMD and try to prioritize the most potential causal risk factors for BMD. Results: Our analysis identified three risk factors T2D, FG, and HCadjBMI for FN BMD; four risk factors FI, T2D, HCadjBMI, and WCadjBMI for FA BMD; and three risk factors FI, T2D, and HDL cholesterol for LS BMD, and all risk factors were causally associated with heel BMD except for triglycerides and WCadjBMI. Consistent with the mvMR results, MR-BMA confirmed those risk factors as top risk factors for each BMD trait individually. Conclusions: By combining MR approaches, we identified the potential causal risk factors for FN, FA, LS, and heel BMD individually and we also prioritized and ranked the potential causal risk factors for BMD, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases. [ABSTRACT FROM AUTHOR]

The mobility of dislocation loops in materials is a principle factor in understanding the mechanical strength, and the evolution of microstructures due to deformation and radiation. In body-centered cubic (BCC) iron, the common belief is that <100> interstitial dislocation loops are immobile once formed. However, using self-adaptive accelerated molecular dynamics (SSAMD), a new diffusion mechanism has been discovered for <100> interstitial dislocation loops. The key aspect of the mechanism is the changing of the habit planes between the {100} plane and the {110} plane, which provides a path for the <100> loops to diffuse one-dimensionally. The migration behavior modeled with SSAMD is further confirmed by in-situ transmission electron microscopy (TEM) measurements, and represents a significant step for understanding the formation of <100> loop walls and the mechanical behavior of BCC Fe under irradiation. The mobility of dislocation loops in materials is of key importance to understanding their deformation behavior. Here the authors using self-adaptive accelerated molecular dynamics show self-diffusion of <100> interstitial loops in body-centered cubic (BCC) iron by changing its habit plane as also confirmed by transmission electron microscopy (TEM) measurements. [ABSTRACT FROM AUTHOR]

Summary: Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits. Introduction: Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS. Methods: We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively. Results: SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10−8) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10−10, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10−8, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development. Conclusion: Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture. [ABSTRACT FROM AUTHOR]

Purpose: Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers' features and discussed potential therapeutic implications.Methods: A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT).Results: Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies.Conclusion: Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling. [ABSTRACT FROM AUTHOR]

Nanoindentation experiments are performed at the vicinity of grain boundaries, in Fe-Si tricrystals, to illustrate the existence of a critical stress at which slip transmission occurs across grain boundaries. Such a critical stress can be considered as a grain boundary yield stress and can be quantified within the framework of conventional gradient plasticity theory, enhanced by introducing a new mechanically induced “interface energy” term. The present study takes a first step in trying to provide a physical interpretation for this “far from thermodynamic equilibrium” interface energy term by conducting nanoindentation tests in three Fe-3wt%Si tricrystals, each of which had three distinct types of grain boundary misorientations, namely 22.5°, 42.0° and 44.6°. By relating the experimentally measured grain boundary yield stress to the predictions of interfacial gradient plasticity, it is possible to determine the interface parameter (ξ), which provides a measure of the resistance to slip transmission for each grain boundary examined. In particular, microscopic arguments from standard dislocation theory reveal that ξ depends on both the grain interior properties and the grain boundary structure. The internal length is shown to depend on multiple characteristic lengths of the microstructure, while a new expression is deduced for relating the Hall-Petch slope to both the interface parameter and internal length. [ABSTRACT FROM AUTHOR]

Summary: By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal metabolism.Introduction: Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes.Methods: BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the P values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples.Results: Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants.Conclusions: Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes. [ABSTRACT FROM AUTHOR]

As global warming intensifies, efforts to understand the changes in extreme climate events have increased in recent years. A combined analysis of the changes in extreme temperature and precipitation events is presented in this paper. Using observational data from 1961 to 2015, a set of hotter and wetter (HW) events is defined, and we examine the changes in these events across China. The results show that more HW events occur in Central and Eastern China than in other subregions, especially in South China (SC). The rate of increase in HW events is 2.7 and 1.9 per decade in SC and East China (EC), respectively. In China, most HW events occurred in the last 20 years of the study period, indicating that China entered a period of high-frequency HW events. Indeed, the range in anomalies in the torrential rain days is greater than that of the high-temperature days in Northwest China (NWC), Central China (CC), and EC after the mid- to late 1990s. The opposite pattern is found in Northeast China (NEC), Southwest China-region 1 (SWC1), Southwest China-region 2 (SWC2), and SC. Finally, the increase in HW events in most regions of China is closely associated with warming. [ABSTRACT FROM AUTHOR]

In this study, a traditional tubular reactor and an amplitude-modulated AC power supply were employed to develop a unique practical ozone generator with a widely adjustable ozone concentration and simultaneously a constant ozone yield. The characteristics regarding discharge and ozone generation in oxygen were experimentally investigated in detail. The amplitude-modulated AC waveform consisted of TON (burst of four consecutive AC cycles) and TOFF with a duty cycle of 0.4. The experimental results show that a unique ozone generator can be developed through changing the applied voltage amplitude when an amplitude-modulated AC power supply producing periodic bursts of several consecutive AC cycles during the TON period is used. A quite high and stable ozone yield of 165 ± 16 g/kWh was achieved and a wide range of ozone concentrations could be obtained. Moreover, we observed a very interesting phenomenon that the discharge energy and voltage peak for every AC cycle showed some difference, resulting from the accumulation and release of charge on the dielectric. The first AC cycle had the highest discharge energy and positive voltage peak as well as the lowest negative voltage peak, which was particularly obvious at a high energy density. Additionally, water cooling of the grounded electrode seemed to have a small influence on the basic electrical characteristics of the discharge and had a positive effect on the concentration and yield of ozone due to a reduction in gas temperature in the discharge gap. [ABSTRACT FROM AUTHOR]

Comprehension over the interactions between lithium (Li) atoms and tungsten (W) or molybdenum (Mo) are crucial to improve the wettability of the flowing liquid Li, a candidate plasma facing material in fusion devices, on the surfaces of supported substrate metals. In this work, we utilize first-principles density- functional theory calculations to figure out the adsorption and diffusion properties of Li atoms and clusters on the (111) surfaces of W and Mo. It is found that single Li atom in the fcc-hollow site is the most favored configuration. For the multiple Li atoms adsorption on the substrates, the planar construction is more stable than the stacking one. The electronic structure analysis shows that the lateral interaction between Li atoms is very weak and the binding between Li atom and the substrates is strong; therefore, it can be inferred that the liquid Li is “wetting” intrinsically on the surfaces of the W and Mo substrates. We also investigate the effect of defects (vacancy, H, C, and O) and find that the preexisted vacancy in the substrates has little effect on the wettability; however, the impurities (especially O atom) will hinder the movement of Li atoms on the metal substrates. [ABSTRACT FROM AUTHOR]

Summary: In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels. Introduction: Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis. Methods: To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools. Results: A total of 1070 membrane proteins were identified and quantified. By comparing the proteins' expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB ( p = 0.0021), CD36 ( p = 0.0104), ACTN1 ( p = 0.0381), and ITGB1 ( p = 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including 'ECM-receptor interaction,' 'calcium ion binding,' 'leukocyte transendothelial migration,' and 'reduction of cytosolic calcium levels.' Results from transcriptomic and genomic levels provided additional supporting evidences. Conclusion: Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk. [ABSTRACT FROM AUTHOR]

This is the first systematic report on the preparation and thermoelectric properties of n-type PbFeTe alloys. Iodine-doped n-type PbFeTe polycrystalline was prepared by melting and hot-pressing techniques. The morphology and phase structure of the prepared materials were analyzed by scanning electron microscopy and x-ray diffraction, which indicated that the samples possessed a rock-salt crystal structure and showed a biphase structure. The major phase was the polycrystalline PbTe compound and the second phase was the FeTe compound. The FeTe nano-/micro-precipitates were homogeneously distributed in the PbTe matrix, which is beneficial for the reduction of the lattice thermal conductivity. The effects of the iodine content on the thermoelectric properties of I-doped PbFeTe have been investigated. The measurement results of electrical resistivity, carrier concentration, Seebeck coefficient, and thermal conductivity in the temperature range of 300-850 K indicate that the thermoelectric transport properties of the obtained samples are sensitive to the iodine content. When the concentration of iodine is about 0.6 at.%, the maximum dimensionless figure-of-merit value of ∼0.65 at 800 K was obtained. [ABSTRACT FROM AUTHOR]

Summary: Low bone mineral density (BMD) and osteoporosis have become a public health problem. We found that non-Hispanic white, black, and Asian adults with extremely low education and personal income are more likely to have lower BMD. This relationship is gender-specific. These findings are valuable to guide bone health interventions. Introduction: The evidence is limited regarding the relationship between socioeconomic status (SES) and bone mineral density (BMD) for minority populations in the USA, as well as the relationship between SES and BMD for men. This study explored and examined the relationship between SES and BMD by race/ethnicity and gender. Methods: Data ( n = 6568) from the Louisiana Osteoporosis Study (LOS) was examined, including data for non-Hispanic whites ( n = 4153), non-Hispanic blacks ( n = 1907), and non-Hispanic Asians ( n = 508). General linear models were used to estimate the relationship of SES and BMD (total hip and lumbar spine) stratified by race/ethnicity and gender. Adjustments were made for physiological and behavioral factors. Results: After adjusting for covariates, men with education levels below high school graduate experienced relatively low hip BMD than their counterparts with college or graduate education ( p < 0.05). In addition, women reporting a personal annual income under $20,000 had relatively low hip and spine BMD than their counterparts with higher income level(s) ( p < 0.05). Conclusions: Establishing a conclusive positive or negative association between BMD and SES proved to be difficult. However, individuals who are at an extreme SES disadvantage are the most vulnerable to have relatively low BMD in the study population. Efforts to promote bone health may benefit from focusing on men with low education levels and women with low individual income. [ABSTRACT FROM AUTHOR]

Summary: In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. Introduction: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis. Methods: Here, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes. Results: Of the total of 3796 detected cytosolic proteins, we identified 16 significant ( P < 0.05) and an additional 22 suggestive ( P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration. Conclusions: The combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis. [ABSTRACT FROM AUTHOR]

The Siwanli landslide is located in the middle section of the Dadu River in the eastern part of the Qinghai-Tibet Plateau in a complex regional geological environment. Strong erosion of the river valley has caused numerous rockfalls and slides on both sides of the valley since the Late Pleistocene. A large number of landslide deposits provide the opportunity for examination of the sedimentary and erosional environment along the Dadu River. Identifying the spatial and temporal characteristics of the large, ancient landslides in the Dadu River valley can help improve understanding of the formation mechanism and evolutionary process of ancient and recurrent landslides. In this paper, the formation mechanism of the ancient, complex, and multistage Siwanli landslide is discussed, as well as an important link between river erosion and the formation and evolution of the landslide. In the first stage, the initial landslide blocked the Dadu River, forming a barrier lake, and multistage landslide dam breaches occurred. The entire landslide dam experienced creep deformation, and local minor multistage sliding occurred at the front and middle parts of the initial landslide. Subsequently, a large landslide formed at the scarp of the initial landslide. [ABSTRACT FROM AUTHOR]

Summary: We performed a GWAS of trochanter and intertrochanter bone mineral density (BMD) in the Framingham Heart Study and replicated in three independent studies. Our results identified one novel locus around the associated variations at chromosomal region 3q13.32 and replicated two loci at chromosomal regions 3p21 and 8q24. Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis. Introduction: Hip trochanter (TRO) and intertrochanter (INT) subregions have important clinical relevance to subtrochanteric and intertrochanteric fractures but have rarely been studied by genome-wide association studies (GWASs). Methods: Aiming to identify genomic loci associated with BMD variation at TRO and INT regions, we performed a GWAS utilizing the Framingham Heart Study (FHS, N = 6,912) as discovery sample and utilized the Women's Health Initiative (WHI) African-American subsample ( N = 845), WHI Hispanic subsample ( N = 446), and Omaha osteoporosis study ( N = 971), for replication. Results: Combining the evidence from both the discovery and the replication samples, we identified one novel locus around the associated variations at chromosomal region 3q13.32 ( rs1949542, discovery p = 6.16 × 10, replication p = 2.86 × 10 for INT-BMD; discovery p = 1.35 × 10, replication p = 4.16 × 10 for TRO-BMD, closest gene RP11-384F7.1). We also replicated two loci at chromosomal regions 3p21 ( rs148725943, discovery p = 6.61 × 10, replication p = 5.22 × 10 for TRO-BMD, closest gene CTNNB1) and 8q24 ( rs7839059, discovery p = 2.28 × 10, replication p = 1.55 × 10 for TRO-BMD, closest gene TNFRSF11B) that were reported previously. We demonstrated that the effects at both 3q13.32 and 3p21 were specific to the TRO, but not to the femoral neck and spine. In contrast, the effect at 8q24 was common to all the sites. Conclusion: Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis. [ABSTRACT FROM AUTHOR]

We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation. Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation. To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20–50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses. We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 ( p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation. Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation. [ABSTRACT FROM AUTHOR]

Summary: The molecular mechanism of osteoporosis (OP) in Kashin-Beck disease (KBD) patients was unclear. Our results suggest that KBD and OP shared some common causal genes, functionally involved in skeletal growth and development and chronic inflammation. Our results provide novel clues for clarifying the molecular mechanism of OP in KBD patients. Introduction: KBD is a chronic skeletal disorder with osteopenia and OP. The pathogenesis of OP in KBD patients remains elusive. Methods: A total of 1717 subjects participated in this study. KBD was diagnosed according to the clinical diagnosis criteria of China (GB16395-1996). The bone mineral density (BMD) and bone areas of the ulna and radius, hip, and lumbar (L1-L4) were measured with a Hologic 4500 W dual-energy X-ray absorptiometry scanner. Genotyping was conducted using Affymetrix SNP Array 6.0. Gene expression profiling of peripheral blood mononuclear cells of KBD and OP patients were compared using Affymetrix HG-U133 plus 2.0 arrays and Agilent Human 1A arrays, respectively. Genome-wide association studies (GWAS) were conducted by PLINK. SCEA and DAVID were applied for pleiotropy and functional enrichment analysis, respectively. Results: SCEA analysis observed significant pleiotropic effects between KBD and the ulna and radius BMD ( P value = 5.99 × 10). GWAS meta-analysis identified six candidate genes with pleiotropic effects, including PDGFD, SOX5, DPYD, CTR9, SPP1, and COL4A1. GO analysis identified 16 significant GO shared by KBD and the ulna and radius BMD, involved in cell morphogenesis and apoptosis. Pathway enrichment analysis detected two common pathways for KBD and the ulna and radius BMD, including calcium signaling pathway and vascular smooth muscle contraction pathway. Gene expression analysis detected three up-regulated inflammation-related genes for KBD and OP, including IL1B, IL8, and CCL1. Conclusion: This study reported several candidate genes involved in the development of OP in KBD patients. [ABSTRACT FROM AUTHOR]

Summary: The purpose of the study is to investigate the relationship between sarcopenia and body composition and osteoporosis in cohorts of three different races with a total of 17,891 subjects. Lean mass and grip strength were positively associated with bone mineral densities (BMDs). Subjects with sarcopenia were two times more likely to have osteoporosis compared with normal subjects. Introduction: The relationship between sarcopenia and osteoporosis is not totally clear. First, the present study assessed this relationship by using two different definitions for sarcopenia. Second, we examined the associations of body composition (including muscle mass as a major and important component) and muscle strength on regional and whole-body BMDs. Methods: In total, 17,891 subjects of African American, Caucasian, and Chinese ethnicities were analyzed. Sarcopenia was defined by relative appendicular skeletal muscle mass (RASM) cut points and also by the definition of the European Working Group on Sarcopenia in Older People (low RASM plus low muscle function). Multiple regression analyses were conducted to examine the association of fat mass, lean mass (including muscle mass), and grip strength with regional and whole-body BMDs. Multivariate logistic regression analysis was performed to explore the association between sarcopenia and osteopenia/osteoporosis. Results: BMDs were positively associated with lean mass and negatively associated with fat mass, after controlling for potential confounders. Grip strength was significantly associated with higher BMDs. Each standard deviation (SD) increase in RASM resulted in a ~37 % reduction in risk of osteopenia/osteoporosis (odds ratio (OR) = 0.63; 95 % confidence interval (CI) = 0.59, 0.66). Subjects with sarcopenia defined by RASM were two times more likely to have osteopenia/osteoporosis compared with the normal subjects (OR = 2.04; 95 % CI = 1.61, 2.60). Similarly, subjects with sarcopenia (low muscle mass and low grip strength) were ~1.8 times more likely to have osteopenia/osteoporosis than normal subjects (OR = 1.87; 95 % CI = 1.09, 3.20). Conclusions: High lean mass and muscle strength were positively associated with BMDs. Sarcopenia is associated with low BMD and osteoporosis. [ABSTRACT FROM AUTHOR]

A study of the biology of the predator Clitostethus brachylobus Peng, Ren & Pang 1998 (Coleoptera: Coccinellidae) under different temperature regimes was carried out. It was performed at seven constant temperature regimes (14, 17, 20, 23, 26, 29, and 32°C), under which C. brachylobus was fed with Bemisia tabaci (Homoptera: Aleyrodidae) nymphs reared on Hibuscus rosa-sinensis plants. Results indicated that developmental period of different immature stages decreased with increase in temperature from 17 to 29°C and above 29°C, of eggs, and pupa decreased, while those of the four larval instars increased. Accumulated survival rates were significantly higher at the temperature of 23 and 26°C than at other temperatures. Highest fecundity of C. brachylobus females (252.40 eggs) was recorded at 26°C. Based on these results, life table of C. brachylobus was cons tructed for temperatures in the range of 17-29°C. The innate capacity for increase (rm) and the finite rate of increase (λ) reached their maximu m at 26°C, while the maximu m value of reproductive rate (R0) was obtained at 23°C. The mean length of a generation (T) decreased with increasing temperature. The lower development thresholds of C. brachylobus for the total pre-imaginal development was 9.58°C, whereas the number of degree-days required for the development from egg to adult emergence was 276.5 degree days. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that infection by coxsackievirus B3 (CVB3), a positive-stranded RNA enterovirus, results in the accumulation of insoluble ubiquitin-protein aggregates, which resembles the common feature of neurodegenerative diseases. The importance of protein aggregation in viral pathogenesis has been recognized; however, the underlying regulatory mechanisms remain ill-defined. Transactive response DNA-binding protein-43 (TDP-43) is an RNA-binding protein that has an essential role in regulating RNA metabolism at multiple levels. Cleavage and cytoplasmic aggregation of TDP-43 serves as a major molecular marker for amyotrophic lateral sclerosis and frontotemporal lobar degeneration and contributes significantly to disease progression. In this study, we reported that TDP-43 is translocated from the nucleus to the cytoplasm during CVB3 infection through the activity of viral protease 2A, followed by the cleavage mediated by viral protease 3C. Cytoplasmic translocation of TDP-43 is accompanied by reduced solubility and increased formation of protein aggregates. The cleavage takes place at amino-acid 327 between glutamine and alanine, resulting in the generation of an N- and C-terminal cleavage fragment of ~35 and ~8 kDa, respectively. The C-terminal product of TDP-43 is unstable and quickly degraded through the proteasome degradation pathway, whereas the N-terminal truncation of TDP-43 acts as a dominant-negative mutant that inhibits the function of native TDP-43 in alternative RNA splicing. Lastly, we demonstrated that knockdown of TDP-43 results in an increase in viral titers, suggesting a protective role for TDP-43 in CVB3 infection. Taken together, our findings suggest a novel model by which cytoplasmic redistribution and cleavage of TDP-43 as a consequence of CVB3 infection disrupts the solubility and transcriptional activity of TDP-43. Our results also reveal a mechanism evolved by enteroviruses to support efficient viral infection. [ABSTRACT FROM AUTHOR]

Summary: Peripheral blood monocytes (PBMs) are an important source of precursors of osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that have profound effects on osteoclast differentiation, activation, and apoptosis. So PBMs represent a highly valuable and unique working cell model for bone-related study. Finding an appropriate working cell model for clinical and (epi-)genomic studies of human skeletal disorders is a challenge. Peripheral blood monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells. Particularly, PBMs provide the sole source of osteoclast precursors for adult peripheral skeleton where the bone marrow is normally hematopoietically inactive. PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important for osteoclast differentiation, activation, and apoptosis. Reduced production of PBM cytokines represents a major mechanism for the inhibitory effects of sex hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have been linked to various skeletal disorders/traits, strongly supporting for the biological relevance of PBMs with bone metabolism and disorders. Here, we briefly review the origin and further differentiation of PBMs. In particular, we discuss the close relationship between PBMs and osteoclasts, and highlight the utility of PBMs in study the pathophysiological mechanisms underlying various skeletal disorders. [ABSTRACT FROM AUTHOR]

The thermal conductivity of a representative endothermic hydrocarbon aviation kerosene fuel RP-3 was accurately measured using the classical transient hot-wire method at sub- and supercritical pressures. The measured data cover a temperature range of 285 K to 513 K and a pressure range of 0.1 MPa to 5 MPa. The expanded uncertainty of the experiment was less than 3.0 % based on an uncertainty analysis. Furthermore, the measured data were correlated using a polynomial equation to analyze the deviations; 97.6 % of the measured data were within a 2 % error band. The average absolute deviation ( AAD) and maximum absolute deviation ( MAD) of the fitted thermal-conductivity data were 0.209 % and 2.31 % for all values, respectively. [ABSTRACT FROM AUTHOR]

Background:The effective mechanisms of microRNAs (miRNAs) functions as oncogenes or tumour suppressors in human hepatocellular carcinoma (HCC) are still obscure. Here, we investigated the function and expression of miR-1228 in HCC.Methods:The role of miR-1228 in HCC was determined by colony formation, transwell, and nude mice xenograft experiments. miR-1228 target gene were identified by EGFP reporter assays, real-time PCR, and western blot analysis. Dual-luciferase reporter assay and real-time PCR analysis are used to examine the regulation of p53.Results:miR-1228 promoted proliferation and metastasis, and facilitated the transition of cell cycle in hepatoma cells. miR-1228 downregulated p53 expression by binding to its 3′UTR. The ectopic expression of p53 abrogated the phenotypes induced by miR-1228. An inverse correlation existed between miR-1228 and p53 expression in hepatoma tissues compared with the adjacent tissues and three hepatoma cell lines. Moreover, we found that p53 suppressed the expression and promoter activity of miR-1228.Conclusions:miR-1228 functions as an oncogene by promoting cell cycle progression and cell mobility and negatively regulates the expression of p53. p53 downregulation in turn leads to an increase in miR-1228 expression, thereby forming a positive feedback loop that contributes to cancerogenesis in HCC. [ABSTRACT FROM AUTHOR]

Collision accidents often occur during parking or reversing cars. In allusion to this point, this paper conducts a review of literatures on automatic parking. To begin with, a brief introduction of automatic parking including its background and significance is given. Then its commercial application, research status and latest progress are summarized which include visual perception, ultrasonic sensors and radar technology, path planning, control algorithms based on fuzzy theory, neural network, image processing and recognition technology, and digital signal processing technology, etc. On further analysis, some reasonable conclusions are drawn and the future work is suggested. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the tumor specificity, cytotoxicity and the antitumor activity of two conditionally replicating oncolytic adenoviruses, SKL001 and SKL002, which expressed granulocyte macrophage colony-stimulating factor (GM-CSF) or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA4) antibody, respectively, and determine their antitumor efficacy in A549 lung tumor model, B16F10 mouse melanoma tumor model and CMT-64 mouse small lung carcinoma tumor model. Virus yield and cytotoxicity were used to determine tumor specificity and virus replication-mediated cytotoxicity of SKL001 and SKL002 in a panel of human tumor cell lines and primary cells in vitro. Two subcutaneous (s.c.) tumor nexograft tumor models were used to assess their antitumor activity. Under the control of the E2F promoter, the expression of E1a genes appeared only in tumor cells, whereas the wild-type Ad5 expressed its E1a genes in both tumor cells and normal cells. GM-CSF and anti-CTLA4 production were significantly higher in tumor cells than normal cells. SKL001 and SKL002 replicated in Rb-defective cell lines as efficiently as wild-type adenovirus but produced 100-fold less virus in normal human cells. SKL001 and SKL002 was up to 1000-fold more cytotoxic in Rb pathway-defective human tumor cells in comparison with normal human cells. Antitumor activity of SKL001 and SKL002 following intravenous administration was shown in a human lung A549 s.c. xenograft tumor model and mouse B16F10 melanoma tumor model when compared with phosphate-buffered saline treatment. In immune-competent mice, the addition of GM-CSF produced a stronger antitumor activity and induced a higher number of mature dendritic cells and macrophages, whereas additive antitumor activity was observed in the group when SKL001 and SKL002 were combined. In vitro and in vivo studies showed the selective replication, cytotoxicity, gene production and antitumor efficacy of SKL001 and SKL002 in human tumor model, suggesting a potential utility of this oncolytic agent for the treatment of human cancer. Further studies are warranted to show the role of human GM-CSF and anti-CTLA4 antibody in the antitumor efficacy of these two oncolytic viruses. [ABSTRACT FROM AUTHOR]

Background:TAp63 is a tumour-suppressor protein that is often underexpressed in various types of cancer. It has been shown to activate gene transcription depending on the transcription domain and to be closely related with metastasis. In this study, we demonstrate that TAp63 suppresses metastasis in colon cancer cells through microRNA-133b.Methods:We evaluated the correlation of TAp63 and miR-133b with HT-29 and SW-620 cells and investigated the roles of TAp63 in the expression of RhoA, E-cadherin and vimentin. We further investigated the roles of TAp63-mediated invasion and migration of colon cancer cells.Results:TAp63 expression is downregulated in colon cancer, and microRNA-133b is a transcriptional target of TAp63. Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin. Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b. Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.Conclusions:TAp63 and microRNA-133b were able to suppress the metastasis of colon cancer. Both TAp63 and microRNA-133b may be potential biomarkers for diagnosis in colon cancer metastasis and may provide unique therapeutic targets for this common malignancy. [ABSTRACT FROM AUTHOR]

The interference pattern of coherent diffraction radiation (CDR) from a silt target is measured using the extracted beam of the microtron at Tomsk Polytechnic University. A theoretical interference pattern is calculated based on a model developed earlier for calculating the CDR characteristics in the far and near zones with allowance for the detector-sensitivity function. Comparison of the theoretical and experimental interference patterns makes it possible to obtain information about the longitudinal size of the bunch. The results obtained by the proposed and earlier methods agree well with each other. [ABSTRACT FROM AUTHOR]

The two membrane-bound proteins, focal adhesion kinase (FAK) and CD44, are involved in processes critical to cancer progression. FAK has an active role in angiogenesis, cell proliferation and cell apoptosis, whereas the heavily glycosylated CD44 has been implicated in cancer metastasis. Here, using short hairpin RNA (shRNA) against FAK and CD44, we demonstrate that simultaneous knockdown of both these genes inhibits cancer growth more efficiently than knockdown of either gene individually. Plasmids targeting these genes or non-relative control sequences were constructed and delivered to ovarian cancer targets by biodegradable poly D,L-lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Single gene knockdown resulted in significantly smaller tumors than those observed in the empty-vector control (P's<0.001). More importantly, knockdown of both genes resulted in tumors smaller than both the empty-vector group (P<0.0001) and the single gene knockdown groups (P's<0.001). Knockdown of both FAK and CD44 resulted in tumors with inhibited angiogenesis, reduced proliferation and increased apoptosis as compared with controls (P's<0.001) and single knockdown groups (P's<0.05). These results indicate that dual knockdown of FAK and CD44 in the tumors of patients with ovarian cancer may have an enhanced therapeutic effect, and point toward a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Transfection of plasmid vectors coexpressing short hairpin RNA (shRNA) for focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) significantly inhibited protein level of FAK and EGFR. Knockdown of FAK and EGFR expression significantly inhibited cell proliferation and induced cell apoptosis of A549 lung cancer cells in vitro. In A549 subcutaneous xenograft model, mice treated for 3 weeks with plasmid that coexpresses FAK and EGFR shRNA had significantly smaller tumors than those in control mice (P<0.01). FAK and EGFR dual silencing also significantly decreased microvessel density, tumor cell proliferation and increased the level of apoptosis in tumor cells. Moreover, administration with plasmid that coexpresses FAK and EGFR shRNA significantly inhibited the A549 experimental lung metastases. Collectively, our data suggest that the dual inhibition of FAK and EGFR by using plasmid vector-based RNA interference might be a novel therapeutic approach to the treatment of human NSCLC. [ABSTRACT FROM AUTHOR]

Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Summary: We tested whether two genetic variants were associated with BMD at multiple clinically relevant skeletal sites in Caucasians. We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis. Introduction: A recent genome-wide association study identified two single nucleotide polymorphisms (SNPs), rs7776725 and rs1721400, that were associated with bone mineral density (BMD) variation at the radius, tibia and calcaneus in a Korean population. In this study, we aimed to test whether the association of these two genetic variants can be replicated in Caucasians and whether their association with BMD can be extended to other clinically relevant skeletal sites. Methods: We performed this study in two large cohorts of unrelated US Caucasians. Area BMD at the hip, spine, wrist (ultra-distal radius) and whole body were measured with Hologic dual-energy X-ray absorptiometer. SNPs were genotyped with Affymetrix human genome-wide genotyping arrays. Association analyses were performed using PLINK. Results: We detected highly significant association (combined p = 1.42 × 10) of rs7776725 with wrist BMD but only borderline association signal (combined p = 0.017) for rs1721400 with wrist BMD. In addition, we found that rs7776725 was associated with BMD at the hip, spine and whole body. At the FAM3C gene locus where rs7776725 was located, we identified several other SNPs (rs4727922, rs1803389, rs718766 and rs7793554) that were also associated with BMD. Conclusions: This is the first follow-up association study of rs7776725 and rs1721400 with BMD. The rs7776725 showed consistent association with BMD at multiple clinically important skeletal sites, which highlighted the potential importance of rs7776725 or linked SNPs for risk of osteoporosis. Further in-depth re-sequencing studies and functional assays are necessary to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Free-electron lasers have been successfully operated with ultrahigh brightness and excellent transverse coherence at X-ray wavelengths. One of the next goals for further improvements is full coherence. An obvious approach is to seed the free-electron laser interaction using a conventional source that has good temporal coherence. Here, we show the first lasing of a free-electron laser with an echo-enabled harmonic generation scheme, which shows great promise for producing coherent lasing at short wavelengths, even in the X-ray regime. The experiment was conducted at a test facility that combines a 135.4 MeV electron accelerator with an amplifier consisting of a series of undulator magnets. Lasing was achieved at the third harmonic of the seed with a gain of ?100,000 over spontaneous radiation. The measurements show typical exponential growth and excellent spectral characteristics, as well as good intensity stability. [ABSTRACT FROM AUTHOR]

Summary: Given the biological function of SOX6 and recent genome-wide association finding, we performed a fine-mapping association analyses to investigate the relationship between SOX6 and BMD both in Caucasian and Chinese populations. We identified many single-nucleotide polymorphisms (SNPs) within or near the SOX6 gene to be significantly associated with hip bone mineral density (BMD). Introduction: SOX6 gene is an essential transcription factor in chondrogenesis and cartilage formation. Recent genome-wide association studies (GWAS) detected a SNP (rs7117858) located at the downstream of SOX6 significantly associated with hip BMD. Methods: Given the biological function of SOX6 and the GWAS finding, we considered SOX6 as a new candidate for BMD and osteoporosis. Therefore, in this study, we performed a fine-mapping association analyses to investigate the relationship between SNPs within and near the SOX6 gene and BMD at both hip and spine. A total of 301 SNPs were tested in two independent US Caucasian populations (2,286 and 1,000 unrelated subjects, respectively) and a Chinese population (1,627 unrelated Han subjects). Results: We confirmed that the previously reported rs7117858-A was associated with reduced hip BMD, with combined P value of 2.45 × 10. Besides this SNP, we identified another 19 SNPs within or near the SOX6 gene to be significantly associated with hip BMD after false discovery rate adjustment. The most significant SNP was rs1347677 located at the intron 3 ( P = 3.15 × 10). Seven additional SNPs in high linkage disequilibrium with rs1347677 were also significantly associated with hip BMD. SNPs in SOX6 showed significant skeletal site specificity since no SNP was detected to be associated with spine BMD. Conclusion: Our study identified many SNPs in the SOX6 gene associated with hip BMD even across different ethnicities, which further highlighted the importance of the SOX6 gene influencing BMD variation and provided more information to the understanding of the genetic architecture of osteoporosis. [ABSTRACT FROM AUTHOR]

Telomere maintenance is essential for cancer growth. Induction of telomere dysfunction, for example, by inhibition of telomeric proteins or telomerase, has been shown to strongly enhance cancer cells' sensitivity to chemotherapies. However, it is not clear whether modulations of telomere maintenance constitute cancer cellular responses to chemotherapies. Furthermore, the manner in which anti-cancer drugs affect telomere function remains unknown. In this study, we show that anthracyclines, a class of anti-cancer drugs widely used in clinical cancer treatments, have an active role in triggering telomere dysfunction specifically in telomerase-positive cancer cells. Anthracyclines interrupt telomere maintenance by telomerase through the downregulation of PinX1, a protein factor responsible for targeting telomerase onto telomeres, thereby inhibiting telomerase association with telomeres. We further demonstrate that anthracyclines downregulate PinX1 by inducing this protein degradation through the ubiquitin-proteasome-dependent pathway. Our data not only reveal a novel action for anthracyclines as telomerase functional inhibitors but also provide a clue for the development of novel anti-cancer drugs based on telomerase/telomere targeting, which is actively investigated by many current studies. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The generation of induced pluripotent stem cells (iPSCs) provides a promising possibility for type 1 diabetes therapy. However, the generation of insulin-producing cells from iPSCs and evaluation of their efficacy and safety should be achieved in large animals before clinically applying iPSC-derived cells in humans. Here we try to generate insulin-producing cells from rhesus monkey (RM) iPSCs. Methods: Based on the knowledge of embryonic pancreatic development, we developed a four-stage protocol to generate insulin-producing cells from RM iPSCs. We established a quantitative method using flow cytometry to analyse the differentiation efficiency. In addition, to evaluate the differentiation competence and function of RM iPSC-derived cells, transplantation of stage 3 and 4 cells into immunodeficient mice was performed. Results: RM iPSCs were sequentially induced to definitive endoderm (DE), pancreatic progenitors (PP), endocrine precursors (EP) and insulin-producing cells. PDX1 PP cells were obtained efficiently from RM iPSCs (over 85% efficiency). The TGF-β inhibitor SB431542 promoted the generation of NGN3 EP cells, which can generate insulin-producing cells in vivo upon transplantation. Finally, after this four-stage differentiation in vitro, insulin-producing cells that could secrete insulin in response to glucose stimulation were obtained. When transplanted into mouse models for diabetes, these insulin-producing cells could decrease blood glucose levels in approximately 50% of the mice. Conclusions/interpretation: We demonstrate for the first time that RM iPSCs can be differentiated into functional insulin-producing cells, which will provide the basis for investigating the efficacy and safety of autologous iPSC-derived insulin-producing cells in a rhesus monkey model for type 1 diabetes therapy. [ABSTRACT FROM AUTHOR]

InAs films with different thicknesses were fabricated on (100)-oriented InAs substrate by liquid phase epitaxy supercooling technique using the sliding graphite boat. The X-ray diffraction measurement shows that films exhibit (100)-preferred crystal orientation. The film thickness dependence on the growth time and cooling rate was investigated by scanning electron microscope and the growth kinetics was analyzed based on one-dimensional diffusion theory. The experimental data were fitted very well by the supercooling equation, and the fitted diffusion coefficient at 520 °C was 6.2 × 10 cm/s. The newly observed mosaic morphology was probably caused by the shake of the growth solution due to sliding the graphite boat. [ABSTRACT FROM AUTHOR]