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A notable example due to Heier, Lu, Wong, and Zheng shows that there exist compact complex Kähler manifolds with ample canonical line bundle such that the holomorphic sectional curvature is negative semi‐definite and vanishes along high‐dimensional linear subspaces in every tangent space. The main result of this note is an upper bound for the dimensions of these subspaces. Due to the holomorphic sectional curvature being a real‐valued bihomogeneous polynomial of bidegree (2,2) on every tangent space, the proof is based on making a connection with the work of D'Angelo on complex subvarieties of real algebraic varieties and the decomposition of polynomials into differences of squares. Our bound involves an invariant that we call the holomorphic sectional curvature square decomposition length, and our arguments work as long as the holomorphic sectional curvature is semi‐definite, be it negative or positive. [ABSTRACT FROM AUTHOR]

An experimental study was carried out to examine the antifouling effect of compound treatment with ultrasonic and magnetic fields simultaneously in convection heat transfer process. The ultrasonic was provided with a frequency of 20 kHz and powers up to 240 W, and the magnetic field was applied with field intensity of 0.25 T and 0.4 T, respectively. The results showed that the ultrasonic treatment presented a good antifouling effect in flow and heat transfer of hard water, and further the combined treatment of the ultrasonic and magnetic displayed much better performance in scale inhibition of convection heat transfer, in which the scale-inhibition efficiency got up to a maximum of 93.9%. The water treatment not only presented the good scale-inhibition effect but also had the morphology of fouling crystal changed. The crystal of calcium carbonate was mainly comprised of the dense calcite with a cubic shape for the case untreated but transformed to the slender aragonite branchlike after the treatment, and the aragonite became longer with the compound treatment. The experimental phenomenon was also discussed for understanding of the mechanism of the technical treatment, which may be referenced to the antifouling application in heat exchanger. [ABSTRACT FROM AUTHOR]

Background: Tumor cell metabolic reprogramming is crucial for the malignant behavior of cancer cells by promoting their proliferation. However, little is known on how transient receptor potential 7 (TRPM7) modulates metabolic reprogramming in ovarian cancer. Methods: The effects of TRPM7 silencing on transcriptome profile, glucose uptake, lactic acid production, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), intracellular ROS and ATP levels, and NAD+/NADH ratios in ovarian cancer cells were examined. The impacts of TRPM7 silencing on the levels of glycolysis-related HK2, PDK1 and oxidative phosphorylation (OXPHOS)-related IDH3B and UQCRC1, HIF-1α expression and AMPK phosphorylation were determined in ovarian cancer. The effect of AMPK activity on HIF-1α ubiquitination degradation was investigated in ovarian cancer cells. Results: Compared with the control, TRPM7 silencing suppressed the proliferation of ovarian cancer cells by shifting preferable glycolysis to OXPHOS. In parallel, TRPM7 silencing decreased the glucose uptake of tumor-bearing mice and TRPM7 levels were negatively correlated with IDH3B and UQCRC1, but positively with HK2 and PDK1 expression in ovarian cancer tissues. Mechanistically, TRPM7 silencing significantly increased AMPK phosphorylation and decreased HIF-1α protein levels in ovarian cancer, particularly in HIF-1α silencing cells. The shifting from glycolysis to OXPHOS by TRPM7 silencing was abrogated by HIF-1α over-expression and impaired by inhibiting AMPK activity in ovarian cancer cells. Moreover, enhanced AMPK activation inhibited glycolysis, which was abrogated by HIF-1α over-expression in ovarian cancer cells. Moreover, the enhanced AMPK activation promoted HIF-1α ubiquitination degradation. Conclusions: TRPM7 silencing enhanced AMPK activation to shift glycolysis to oxidative phosphorylation by promoting HIF-1α ubiquitination degradation in ovarian cancer. Hence, TRPM7 may be a therapeutic target for intervention of ovarian cancer. [ABSTRACT FROM AUTHOR]

An experimental study on the antifouling performance of ultrasonic and/or electronic treatment was carried out in a convective heat transfer process by using a fouling monitor system. An ultrasonic device was used in a frequency of 28 kHz and a power of 80 W, and a low-voltage electronic processor also used with a maximum current of 0.8 A for water treatment. The experimental results showed that both of the ultrasonic and the electronic treatment, all displayed good scale-inhibition effects for hard water in convective heat transfer, and further the compound treatment of them gave much better antifouling performance at the same conditions. The fouling inhibition efficiency got up to a maximum of 100% by the treatments. The technical treatment may change not only the amount of deposition on heat transfer surface, but also the morphology of crystals formed in microscale. The fouling crystal displayed a clear type of aragonite of calcium carbonate but varied obviously with the treatments. It can be sure that the technical treatments are effective and applicable in real heat transfer application with hard water as a working fluid. [ABSTRACT FROM AUTHOR]

Based on a modification of a magnetohydrodynamic turbulence model, a numerical study was performed to investigate the effects of transverse uniform and gradient magnetic field on the turbulent flow and heat transfer characteristics of a low melting point molten salt in a stainless steel pipe. With the Hartmann number from 0 to 80, the numerical results showed that the fluid flow displayed anisotropic distributions under the magnetic field with decrease of velocity in the mainstream region, and decrease of turbulent intensity, whereas the flow velocity increased in the boundary layer near the Hartmann and Roberts wall. Especially, a velocity jet phenomenon was observed in the Roberts boundary layers at higher Hartmann number in the uniform magnetic field or the positive gradient magnetic field. Under the gradient magnetic field, the flow and heat transfer of molten salt displayed much more variations than under the uniform magnetic field. The magnetohydrodynamic calculation results proposed here might be helpful to the design of the composite heat transfer system for molten salt in actual industrial applications. • Both the uniform and non-uniform magnetic field were applied in pipe flow of molten salt for comparison. • A modified MHD turbulence model was established for turbulent flow of molten salt. • The characteristics of flow and heat transfer were numerically studied for a low melting point molten salt. • The complex influence of magnetic field to flow and heat transfer of molten salt was observed. [ABSTRACT FROM AUTHOR]

A synthesis of two prevailing global navigation satellite system positioning technologies, namely the precise point positioning and the network-based real-time kinematic, results in the emergence of the PPP-RTK, enabling single-receiver users to achieve high positioning accuracy with reasonable timeliness through integer ambiguity resolution. The realization of PPP-RTK needs to accomplish two sequential tasks. The first task is to determine a class of corrections including, among others, the satellite phase biases (SPBs) at the network level. With these corrections, the second task, then, is to solve for the ambiguity-fixed, absolute position at the user level. In this contribution, we revisit three variants (geometry-free, geometry-fixed and geometry-plus-satellite-clock-fixed) of the undifferenced and uncombined PPP-RTK network model and then point out their implications for practical use. We also carry out a case study using multi-day, dual-frequency global positioning system data from the crustal movement observation network of China stations, aiming to figure out what are the most appropriate linear combinations of the SPBs to be transmitted to the users from the viewpoint of decorrelation, and to assess the static and kinematic positioning performance. [ABSTRACT FROM AUTHOR]

In order to investigate the heat transfer characteristics of mixed molten salt, an experimental setup for the submerged jet impingement has been established in this paper. Firstly, an experimental investigation on heat transfer of submerged jet impingement with water as working fluid was carried out to verify reliability of experimental method. A good consistence was found between experimental results and those classical correlations from references for stagnation heat transfer, which indicate the reliability and accuracy of experimental method. On the basic of ensuring the reliability of experiment, a series of studies on jet impingement experiments were carried out with new mixed molten salt. The results indicated that effect of submerged jet impingement heat transfer enhanced gradually with the increase Reynolds number and the heat transfer characteristics at the stagnation are analogous with the water in the scope of experimental investigations. Further, a correlation about quaternary mixed molten salt was proposed based on experimental data. At same Reynolds number, the Nusselt number of mixed molten salt is obviously higher than that of water at stagnation zone because of its higher Prandtl number and becomes lower than water at larger radial distance due to its higher viscosity. The results indicated that thermophysical properties of working fluid have an enormous influence on the Heat transfer performance. The experimental results in this paper provide a necessary technical guarantee for the study of heat transfer of the high temperature fluid. [ABSTRACT FROM AUTHOR]

In this paper, a prediction model for the crystallization fouling was proposed on the basis of the Kern-Seaton model for the heat transfer and fouling process in circulated cooling water. The fouling deposition and removal process were analyzed, respectively, for the fouling process, on which the coupling effects of the scale layer, temperature and ions concentration were considered. The model calculation may predict the fouling resistance variations in fouling process, which were in good agreement with experimental data from references within a range of given conditions especially for the turbulent flow, indicating the model applicability for actual process. Since the model can be used without requirement of a large amount of measured data for fitting, it gives a more convenient way for predicting fouling process of heat exchangers in industry. • A prediction model for CaCO 3 crystallization fouling in circulating cooling water was established. • The fouling deposition and removal processes were all analyzed in the model respectively. • The coupling effects of fouling layer, temperature and concentration of fouling ions were considered. • The calculation of model may provide a fouling prediction without requirement of a number of experimental data for fitting. [ABSTRACT FROM AUTHOR]

The content authenticity is critical for secure transmission of multimedia information. As a promising solution, perceptual image hashing has gain great attention. In this paper, we develop a novel algorithm for generating an image hash based on invariants of radial Tchebichef moments. The idea is justified by the fact that the radial Tchebichef moments represent the image under the orthogonal kernel, which has the desirable qualities of orthogonality and robustness. The hash values are achieved by adaptive quantization of the invariants of radial Tchebichef moments, then the random Gay code is applied in the discrete–binary conversion stage to enhance the expected discriminability. Experiments are conducted to show that the proposed hashing algorithm has superior robustness and discrimination performance compared with other state-of-the-art algorithms, in terms of receiving operating characteristic (ROC) curves. [ABSTRACT FROM AUTHOR]

Abstract: Ethene hydrogenation reaction, catalyzed by an iridium atom adsorbed on γ-Al2O3(001) surface, is studied via ab initio calculations based on density functional theory (DFT). The catalyzed reaction process and activation energy are compared with the counterparts of a reaction occurs in vacuum condition. It is found that the activation energy barrier is substantially lowered by the adsorbed Ir atom on the γ-Al2O3(001). The catalyzed reaction is modeled in two steps: (1) Hydrogen molecular dissolution and then bonded with C2H4 molecular. (2) Desorption of the C2H6 molecular from the surface. [Copyright &y& Elsevier]

Much effort has been focused on improving assisted reproductive technology procedures in humans and nonhuman primates ( NHPs). However, the pregnancy rate after embryo transfer ( ET) has not been satisfactory, indicating that some barriers still need to be overcome in this important procedure. One of the key factors is embryo-uterine synchronicity, which is little known in NHPs. The objective of this study was to investigate the available ET time window in rhesus monkey ( Macaca mulatta). Eighty-two adult female rhesus monkeys were superovulated with recombinant human FSH. Ovarian phases were identified according to estrogen (E2) and progesterone (P4) levels as well as ovarian examination by ultrasonography and laparoscopy. A total of 259 embryos were transferred by the laparoscopic approach into the oviducts of 63 adult female monkeys. Ovarian phases were divided into late follicular and early luteal phases. Similar pregnancy rates (30-36.4%) were obtained from recipients receiving ET either in their late follicular or early luteal phases, regardless of embryo developmental stages. This study indicates that the available time window for ET in rhesus monkeys is from the late follicular to early luteal phases. [ABSTRACT FROM AUTHOR]

An innovative physical method to control fouling in heat transfer equipment—low voltage electrolysis anti-fouling (LVEAF) technology—is introduced. The objective of the present study is to testify the effect of LVEAF treatment in forced convective system and identify the operating mechanism. A series of fouling tests were carried out with and without LVEAF treatment. During the experiments fouling resistance was monitored, and the properties of test liquid were measured, including hardness, alkalinity, electrical conductivity, and pH. The main results were as follows: (1) The fouling was effectively restrained to form on the heat exchanger surface if the circulating water was treated with LVEAF. The scale inhibition ratios exceeded 90% in most cases. (2) The LVEAF technology is an active anti-fouling technology with lower energy consumption. The properties of treated test liquid were changed. (3) Electrochemical reactions occur near the electrode due to the low current existence in the water when the LVEAF device is working. A lot of fouling deposits formed in the test liquid near the cathode or on the inner surface of the treatment unit, but did not deposit on the heat exchanger surface. [ABSTRACT FROM AUTHOR]

Abstract: Iridium adsorption on γ-Al2O3 (001) surface has been studied using the ab initio calculation method and the electronic structures of the bare and the Ir adsorbed γ-Al2O3 (001) surfaces have been analyzed. By modeling different adsorption sites, one can conclude that the energetically most favorable sites for the Ir are the top sites of the O atoms at the γ-Al2O3 (001) surface terminated with octahedral Al. Charge redistribution around the Ir atom adsorbed on the surface improves the activity of the Ir atom as a catalyst. [Copyright &y& Elsevier]

Background: Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. Methods: We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. Results: IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). Conclusion: IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC. [ABSTRACT FROM AUTHOR]

• An experimental setup for free-surface jet impingement heat transfer of molten salt. • A new correlation of stagnation heat transfer with molten salt proposed. • Heat transfer characteristics of molten salt along heat transfer surface obtained. An experimental study of free-surface jet impingement was carried out with compound molten salt to understand its characteristics of heat transfer. Based on pre-experimental verification on the reliability of experimental method by water as working fluid, a compound molten salt was chosen as a new working fluid to conduct experiment of free-surface jet impingement. The heat transfer of molten salt at stagnation point was investigated in detail, and the Nusselt number of molten salt increased with increasing of the Reynolds number and the Prandtl number, and was nearly constant with increasing of nozzle-to-plate spacing at present ranges. The data was correlated by an empirical formula, which was compared with those classical correlations from references. Next, the variation of the Nusselt number of molten salt was also verified along heated surface. It was shown that the local Nusselt number decreased monotonously with increasing of lateral distances from stagnation point, and increased with increasing of the Reynolds number. The profiles of the Nusselt number were nearly unchanged for different nozzle-to-plate spacing, which can be well correlated by a normalized formula. This work focused on the heat transfer characteristics of the molten salt in free-surface jet impingement, which may be recognized as a reference for promoting the application of molten salt in heat transfer process, especially in high temperature situations. [ABSTRACT FROM AUTHOR]

Cortical traumatic brain injury (TBI) is a major cause of cognitive impairment accompanied by motor and behavioral deficits, and there is no effective treatment strategy in the clinic. Cell transplantation is a promising therapeutic strategy, and it is necessary to verify the survival and differentiation of cells after transplantation in large animal models like rhesus monkeys. In this study, we transplanted neural stem cells (NSCs) and simultaneously injected basic fibroblast growth factor/epidermal growth factor (bFGF/EGF) into the cortex (visual and sensory cortices) of rhesus monkeys with superficial TBI. The results showed that the transplanted NSCs did not enter the cerebrospinal fluid (CSF) and were confined to the transplantation site for at least one year. The transplanted NSCs differentiated into mature neurons that formed synaptic connections with host neurons, but glial scar formation between the graft and the host tissue did not occur. This study is the first to explore the repairing effect of transplanting NSCs into the superficial cerebral cortex of rhesus monkeys after TBI, and the results show the ability of NSCs to survive long-term and differentiate into neurons, demonstrating the potential of NSC transplantation for cortical TBI. [ABSTRACT FROM AUTHOR]

• The importance of androgen receptors in prostate cancer. • Application of ncRNAs in the diagnosis and treatment of prostate cancer. • Relationship between ncRNAs and androgen receptor signaling pathways. Prostate cancer (PCa) is one of the most common malignancies for men worldwide, and abnormal activation of the androgen receptor (AR) signaling plays an important role in the progression of PCa. However, in the androgen deprivation therapy (ADT), AR signaling inevitably recovered, as a result, exploring novel regulating mechanisms is of great importance. Recently, non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, circular RNAs, could be involved in the progression of PCa, and participate in the regulatory network of AR signaling in a variety of ways. This will help to identify novel molecular mechanisms to promote the development of PCa and find new potential therapeutic targets. In this review, we provide a synopsis of the latest research relating to ncRNAs and associated AR signaling in PCa. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate the importance of extracapsular extension (ECE) of transitional zone (TZ) prostate cancer (PCa), examine the causes of its missed detection by Mp-MRI, and develop a new predictive model by integrating multi-level clinical variables. Materials and methods: This retrospective study included 304 patients who underwent laparoscopic radical prostatectomy after 12 + X needle transperineal transrectal ultrasound (TRUS)-MRI-guided targeted prostate biopsy from 2018 to 2021 in our center was performed. Results: In this study, the incidence rates of ECE were similar in patients with MRI lesions in the peripheral zone (PZ) and TZ (P = 0.66). However, the missed detection rate was higher in patients with TZ lesions than in those with PZ lesions (P < 0.05). These missed detections result in a higher positive surgical margin rate (P < 0.05). In patients with TZ lesions, detected MP-MRI ECE may have grey areas: the longest diameters of the MRI lesions were 16.5–23.5 mm; MRI lesion volumes were 0.63–2.51 ml; MRI lesion volume ratios were 2.75–8.86%; PSA were 13.85–23.05 ng/ml. LASSO regression was used to construct a clinical prediction model for predicting the risk of ECE in TZ lesions from the perspective of MRI and clinical features, including four variables: the longest diameter of MRI lesions, TZ pseudocapsule invasion, ISUP grading of biopsy pathology, and number of positive biopsy needles. Conclusions: Patients with MRI lesions in the TZ have the same incidence of ECE as those with lesions in the PZ, but a higher missed detection rate. [ABSTRACT FROM AUTHOR]

Summary Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT. [ABSTRACT FROM AUTHOR]

Highlights • Autism is a behaviorally defined neurodevelopmental disease. • Macaques provide unique advantages over rodents to model human autism. • This review focuses on behavioral phenotyping assays for macaque models of autism. Abstract Autism is a behaviorally defined neurodevelopmental disease characterized by social communication and social interaction deficits, as well as repetitive behaviors and restricted interests. Although the causes of autism are extremely complex, involving genes, environments and gene-environment interactions, genetic mutations are the important risk factors. For this reason, preclinical research is now shifting into focusing on generating transgenic and knockout models, especially using macaques, which are the closest relatives to humans. In spite of unique advantages of macaques over rodents in both functionally specialized brain structures and highly sophisticated social behaviors, the limited availability of phenotype screening tools restricts their translational utility. Here, this review focuses specially on behavioral phenotyping assays for macaque models of autism. In the first part, the existing behavioral tests are discussed, and the second part is devoted to some few, in our view, very promising tests of new developments. In years to come, we should develop macaque models with high construct validity, improve face validity by designing more specialized behavioral screening tools, strengthen collaborative efforts between rodent and macaque models, and ultimately translate the results from animal models into human clinical trials. [ABSTRACT FROM AUTHOR]

The performance of real-time (RT) precise positioning can be improved by utilizing observations from multiple Global Navigation Satellite Systems (GNSS) instead of one particular system. Since the end of 2012, BeiDou, independently established by China, began to provide operational services for users in the Asia-Pacific regions. In this study, a regional RT precise positioning system is developed to evaluate the performance of GPS/BeiDou observations in Australia in providing high precision positioning services for users. Fixing three hourly updated satellite orbits, RT correction messages are generated and broadcasted by processing RT observation/navigation data streams from the national network of GNSS Continuously Operating Reference Stations in Australia (AUSCORS) at the server side. At the user side, RT PPP is realized by processing RT data streams and the RT correction messages received. RT clock offsets, for which the accuracy reached 0.07 and 0.28 ns for GPS and BeiDou, respectively, can be determined. Based on these corrections, an accuracy of 12.2, 30.0 and 45.6 cm in the North, East and Up directions was achieved for the BeiDou-only solution after 30 min while the GPS-only solution reached 5.1, 15.3 and 15.5 cm for the same components at the same time. A further improvement of 43.7, 36.9 and 45.0 percent in the three directions, respectively, was achieved for the combined GPS/BeiDou solution. After the initialization process, the North, East and Up positioning accuracies were 5.2, 8.1 and 17.8 cm, respectively, for the BeiDou-only solution, while 1.5, 3.0, and 4.7 cm for the GPS-only solution. However, we only noticed a 20.9% improvement in the East direction was obtained for the GPS/BeiDou solution, while no improvements in the other directions were detected. It is expected that such improvements may become bigger with the increasing accuracy of the BeiDou-only solution. [ABSTRACT FROM AUTHOR]

ZrO2, a traditional inert transition metal oxide (TMO), can be prepared into ZrO2 nanofilms (NFs) with a single-layer thickness of only 2.5 nm through the generally applicable two-dimensional TMO synthesis strategy reported by us, and has displayed remarkable sensitivity and selectivity properties for triethylamine gas detection. [ABSTRACT FROM AUTHOR]

The study of secretory protein kinase is an emergent research field in recent years. The secretion phenomenon of type II cGMP‐dependent protein kinase (PKG II) was found in our latest research and our previous study confirmed that PKG II inhibited platelet‐derived growth factor receptor β (PDGFRβ) activation induced by platelet‐derived growth factor BB (PDGF‐BB) within the gastric cancer cells. Thus, this study was designed to investigated effect of secretory PKG II on PDGFRβ. Transwell assay and CCK8 assay indicated that secretory PKG II reversed PDGF‐BB‐induced cell migration, invasion, and proliferation. Immunoprecipitation, GST pull down and Western blotting results showed that secretory PKG II combined with extracellular domains of PDGFRβ and phosphorylated it, and thereby inhibited PDGF‐BB‐induced activation of PDGFRβ, and downstream PI3K/Akt and MAPK/ERK pathways. Mutation at Ser254 of PDGFRβ to alanine abolished the above inhibitory effects of secretory PKG II on PDGFRβ, indicating that Ser254 was the specific site phosphorylated by secretory PKG II. In conclusion, secretory PKG II inhibited PDGFRβ activation via Ser254 site. [ABSTRACT FROM AUTHOR]

It is a challenge work to estimate the 3D human motion from image sequence. There are some problems, such as unsatisfactory estimation error, ambiguous matching and transient occlusion. Although the prior information of learning large‐scale samples exists, these problems are still difficult to be solved. How to extract the feature of the high‐dimensional (HD) sample of 3D human motion and find the desired one will become the key to solve these problems above. Some dimension reduction methods can extract the sample features and build the low‐dimensional (LD) space to view their LD features, but how to search the relevant valid and desired LD samples remains the bottleneck problem, which can be used to reconstruct the 3D human motions denoted by the corresponding high‐dimensional samples. Thus, a new method called dynamic manifold Boltzmann optimization (DMBO) is proposed to estimate the 3D human motion from multi‐view images. DMBO can find the best matching 3D human motion model by the help of the self‐supervised learning from Gaussian incremental dimension reduction model (GIDRM). DMBO can avoid the local optimum during searching and solve the problems above, so that the generation of the accurate 3D human motion corresponding to multi‐view images can be achieved. [ABSTRACT FROM AUTHOR]

Background: Our previous research results showed that Type II cGMP dependent protein kinase (PKG II) could block the activation of epidermal growth factor receptor (EGFR) and consequently inhibit the proliferation and the related MAPK/ERK-mediated signal transduction of gastric cancer cell line BGC-823, suggesting that PKG II might inhibit other EGFR-triggered signal transduction pathways and related biological activities of gastric cancer cells. This paper was designed to investigate the potential inhibition of PKG II on EGF/EGFR-induced migration activity and the related signal transduction pathways. Methodology/Principal Findings: In gastric cancer cell line AGS, expression and activity of PKG II were increased by infecting the cells with adenoviral construct encoding PKG II cDNA (Ad-PKG II) and treating the cells with cGMP analogue 8-pCPT-cGMP. Phosphorylation of proteins was detected by Western Blotting and active small G protein Ras and Rac1 was measured by “Pull-down” method. Cell migration activity was detected with trans-well equipment. Binding between PKG II and EGFR was detected with Co-IP. The results showed EGF stimulated migration of AGS cell and the effect was related to PLCγ1 and ERK-mediated signal transduction pathways. PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLCγ1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it. Conclusion/Significance: Our results systemically confirms the inhibition of PKG II on EGF-induced migration and related signal transduction of PLCγ1 and MAPK/ERK-mediated pathways, indicating that PKG II has a fargoing inhibition on EGF/EGFR related signal transduction and biological activities of gastric cancer cells through phosphorylating EGFR and blocking the activation of it. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods: An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results: The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19–3.62) times more likely than females to receive the H1N1 vaccination; the 45–54 and 55+ years old were 2.12 (95% CI 1.06–4.24) and 2.44 (95% CI 1.13–5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48–10.92). The 2 principal barriers were “fear of side effects” and “unsure of vaccine''s effectiveness”. Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine''s safety profile and contraindications. Conclusion: Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine''s side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine''s safety profile. [Copyright &y& Elsevier]

[Display omitted] [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that type II cGMP-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF) induced tyrosine phosphorylation/activation of the EGF receptor (EGFR). This paper was designed to investigate the mechanism of the inhibition of PKG II on EGFR activation. Gastric cancer cells HGC-27 and AGS were infected with an adenoviral vector encoding the cDNA of PKG II (Ad-PKG II) to overexpress PKG II and treated with 8-(4-chlorophenylthio) guanosine-3′,5′-cyclic monophosphate (8-pCPT-cGMP) to activate the kinase. Co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assay were performed to detect the interaction between PKG II and EGFR. Western blotting, mass spectrometry (MS) and site mutagenesis were performed to detect the PKG II-specific phosphorylation site on EGFR. The results showed that in living COS-7 cells, which were infected with Ad-PKG II and treated with 8-pCPT-cGMP, there was an interaction between PKG II and EGFR. The results also showed that PKG II caused threonine 669 (T669) phosphorylation of EGFR in HGC-27 and AGS cells infected with Ad-PKG II and treated with 8-pCPT-cGMP, and then inhibited the activation of EGFR. When T669 of EGFR was mutated to alanine, the inhibitory effect of PKG II on the activation of EGFR was eradicated. These findings suggested a PKG II-specific phosphorylation site on EGFR, and might be beneficial to illuminate the anti-tumor role of PKG II. • Interaction between PKG II and EGFR was detected in living cells. • PKG II caused T669 phosphorylation of EGFR. • PKG II inhibited the activation of EGFR via phosphorylating its T669. [ABSTRACT FROM AUTHOR]

Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive. Here, we successfully generated 11 transgenic rhesus monkeys (8 first-generation and 3 second-generation) carrying human copies of MCPH1 , an important gene for brain development and brain evolution. Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation, resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys, similar to the known evolutionary change of developmental delay (neoteny) in humans. Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes, providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task. The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies revealed that type II cGMP‐dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR) which is a widely investigated RTK. PDGFR belongs to family of receptor tyrosine kinases (RTKs) too. However, the effect of PKG II on PDGFR activation is not clear yet. This study investigated potential regulatory effect of PKG II on activation of PDGFRβ and the downstream signaling transductions in gastric cancer. The results from CCK8 assay and Transwell assay indicated that PDGF‐BB induced cell proliferation and migration. Activated PKG II reversed the above variations caused by PDGF‐BB. Immunoprecipitation and Western blotting results showed that PKG II combined with PDGFRβ and phosphorylated this receptor, and thereby inhibited PDGF‐BB induced activation of PDGFRβ, and MAPK/ERK and PI3K/Akt mediated signal transduction pathways. Based on the prediction by phosphorylation site software, Ser643 and Ser712 were mutated to alanine respectively which prevented phosphorylation at these sites. Mutation at Ser712 abolished the inhibitory function of PKG II on PDGFRβ activation but mutation of Ser643 had no such an effect, indicating that Ser712 was PKG II‐specific phosphorylating site of PDGFRβ. In conclusion, PKG II inhibited PDGFRβ activation in gastric cancer via phosphorylating Ser712 of this RTK. [ABSTRACT FROM AUTHOR]

Care should be taken to minimize the adverse impact of differential code biases (DCBs) on global navigation satellite systems (GNSS)-derived ionospheric information determinations. For the sake of convenience, satellite and receiver DCB products provided by the International GNSS Service (IGS) are treated as constants over a period of 24 h (Li et al. (2014)). However, if DCB estimates show remarkable intra-day variability, the DCBs estimated as constants over 1-day period will partially account for ionospheric modeling error; in this case DCBs will be required to be estimated over shorter time period. Therefore, it is important to further gain insight into the short-term variation characteristics of receiver DCBs. In this contribution, the IGS combined global ionospheric maps and the German Aerospace Center (DLR)-provided satellite DCBs are used in the improved method to determine the multi-GNSS receiver DCBs with an hourly time resolution. The intra-day stability of the receiver DCBs is thereby analyzed in detail. Based on 1 month of data collected within the multi-GNSS experiment of the IGS, a good agreement within the receiver DCBs is found between the resulting receiver DCB estimates and multi-GNSS DCB products from the DLR at a level of 0.24 ns for GPS, 0.28 ns for GLONASS, 0.28 ns for BDS, and 0.30 ns for Galileo. Although most of the receiver DCBs are relatively stable over a 1-day period, large fluctuations (more than 9 ns between two consecutive hours) within the receiver DCBs can be found. We also demonstrate the impact of the significant short-term variations in receiver DCBs on the extraction of ionospheric total electron content (TEC), at a level of 12.96 TECu (TEC unit). Compared to daily receiver DCB estimates, the hourly DCB estimates obtained from this study can reflect the short-term variations of the DCB estimates more dedicatedly. The main conclusion is that preliminary analysis of characteristics of receiver DCB variations over short-term intervals should be finished prior to estimate daily multi-GNSS receiver DCB products. [ABSTRACT FROM AUTHOR]

Maternal affiliation by infants is the first social behavior of mammalian animals. We report here that elimination of the Tph2 gene essential for serotonin synthesis in the brain reduced affiliation in mice, rats, and monkeys. Calcium imaging and c-fos immunostaining showed maternal odors activation of serotonergic neurons in the raphe nuclei (RNs) and oxytocinergic neurons in the paraventricular nucleus (PVN). Genetic elimination of oxytocin (OXT) or its receptor reduced maternal preference. OXT rescued maternal preference in mouse and monkey infants lacking serotonin. Tph2 elimination from RN serotonergic neurons innervating PVN reduced maternal preference. Reduced maternal preference after inhibiting serotonergic neurons was rescued by oxytocinergic neuronal activation. Our genetic studies reveal a role for serotonin in affiliation conserved from mice and rats to monkeys, while electrophysiological, pharmacological, chemogenetic, and optogenetic studies uncover OXT downstream of serotonin. We suggest serotonin as the master regulator upstream of neuropeptides in mammalian social behaviors. [Display omitted] • Tph2 gene knockout in mice, rats, or monkeys reduced maternal affiliation by infants • Serotonergic neurons and oxytocinergic neurons were activated by maternal odors • Serotonergic neurons in the RN activate oxytocinergic neurons in the PVN • 5-HT acts upstream of oxytocin in regulating maternal affiliation by infants Maternal affiliation by infants is the first social behavior. Liu et al. have discovered a role for serotonin in this behavior conserved from mice and rats to monkeys. Serotonergic neurons from the raphe nucleus innervates oxytocinergic neurons in the paraventricular nucleus with serotonin acting upstream of oxytocin in maternal affiliation. [ABSTRACT FROM AUTHOR]

Background The overexpression and mutation of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are widespread in cancers and have been recognized as attractive oncologic targets with diverse therapeutic targets. Reports of the overexpression of genes, proteins and mutations of PDGFs/PDGFRs in gastric cancer and their associations with clinicopathological features, Western and Asian patients, as well as prognostic role have shown variable outcomes. This study sought to employ meta-analysis to evaluate PDGFs/PDGFRs status prognostic significance and their association with clinicopathological features of gastric cancer. Method A comprehensive search of PubMed database for studies that investigated the overexpression of mRNA/Protein and mutation of PDGFs/PDGFRs in gastric cancer of Western and Asian patients, their prognostic significance and association with clinicopathological characteristics in May, 2017 or earlier was carried out by two reviewers independently. Pooled odd ratios and hazard ratios at 95% confidence intervals were estimated and summarized using fixed-effect and random-effect Mantel-Haenszel models and Inverse Variance models in Review Manager software version 5.3. Results Fourteen studies with 16 datasets of 1178 patients were included in meta-analysis. Fourteen studies of 1178 patients with 1446 cases and 7 studies of 1076 patients with 1280 cases were included in meta-analysis of clinicopathological and prognostic significance of high or positive PDGF/PDGFR status respectively. Odd ratio at 95% confidence intervals for different groups of analysis are as follows: males versus females(OR = 1.38, 95% CI: 1.04–1.83, P OR  = 0.03); ≥T2 stage versus T1 stage(OR = 2.06, 95% CI: 1.22–3.49, P OR  = 0.007); nodal metastasis versus no nodal metastasis(OR = 2.78, 95% CI: 1.48–5.22, P OR  = 0.002); TNM stage ≥II versus TNM stage I(OR = 3.55, 95% CI: 1.89–6.69, P OR <0.0001). Subgroup analysis of the association of PDGF/PDGFR among Western patients(OR = 0.24 95% CI: 0.10–0.58, P OR  = 0.002) and association of PDGFs/PDGFRs gene mutation among gastric cancer patients(OR = 0.15, 95% CI: 0.05–0.45, P OR  = 0.0008) were significant. The association of PDGFs/PDGFRs in young and middle age versus elderly aged, undifferentiated versus well differentiated tumors, large tumor size group(>6 cm) versus small tumor size group(≤6 cm) were insignificant. Subgroup analysis of the association of PDGFs/PDGFRs among Western Asian patients; PDGF/PDGFR mRNA expression and protein expression among gastric cancer patients were insignificant. In addition, PDGF/PDGFR status among gastric cancer patients was insignificant in overall effect analysis PDGF/PDGFR status has shown to predict reduced overall survival(HR = 1.25, 95% CI: 0.49–3.22, P HR  = 0.64) and relapse free survival(HR = 0.93, 95% CI: 0.36–2.41, P HR  = 0.88) insignificantly. Also, overall prognostic effect analysis(HR = 1.07, 95% CI: 0.58–1.96, P HR  = 0.84) was insignificant. Conclusion PDGFs/PDGFRs status amongst gastric cancer patients plays a key role in clinical variables and nodal metastasis. These insights might be helpful in providing guidelines for diagnosis, molecular target therapy, and prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP‐dependent protein kinase (PKG II) could block the EGF‐EGFR axis as well as down‐stream signaling pathways, for example, MAPK, PI3 K, and PLC in GC cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human GC cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad‐PKG II) to up‐regulate PKG II and then treated with 8‐pCPT‐cGMP. Two‐dimensional electrophoresis (2‐DE) was used to analyze the changes of protein expression in the cells. The results showed that 17 proteins had more than twofold changes in EGF‐treated group compared with control. However, Ad‐PKG II could effectively reversed the changes. Furthermore, far upstream element‐binding protein 1 (FUBP1) and MarvelD3 were chosen and PKG II activation reversed EGF/EGFR‐induced up‐regulation of FUBP1 and downregulation of MarvelD3, respectively. MarvelD3 silence effectively abolished the inhibitory effect of PKG II on EGF‐triggered migration. These data indicated that the inhibitory effect of PKG II partially was associated with MarvelD3. [ABSTRACT FROM AUTHOR]

Shale samples collected from seven wells in the southeastern Ordos Basin were tested to investigate quantitatively the pore structure and fractal characteristics of the Lower Permian Shanxi Shale, which was deposited in a marine-continental transitional (hereinafter referred to as the transitional) environment. Low-pressure nitrogen adsorption data show that the Shanxi Shale exhibits considerably much lower surface area (SA) and pore volume (PV) in the range of 0.6–1.3 m 2 /g and 0.25–0.9 ml/100 g, respectively. Type III kerogen abundant in the transitional Shanxi Shale were observed to be poorly developed in the organic pores in spite of being highly mature, which resulted in a small contribution of organic matter (OM) to the SA and PV. Instead, I/S (illite-smectite mixed clay) together with illite jointly contributed mostly to the SA and PV as a result of the large amount of inter-layer pores associated with them, which were evident in broad-ion-beam (BIB) imaging and statistical analysis. Additionally, the Shanxi Shale has fractal geometries of both pore surface and pore structure, with the pore surface fractal dimension (D1) ranging from 2.16 to 2.42 and the pore structure fractal dimension (D2) ranging from 2.49 to 2.68, respectively. The D1 values denote a pore surface irregularity increase with an increase in I/S and illite content attributed to their more irregular pore surface compared with other mineralogical compositions and OM. The fractal dimension D2 characterizing the pore structure complexity is closely related to the pore arrangement and connectivity, and I/S and illite decrease the D2 when their contents increase due to the incremental ordering degree and connectivity of I/S- or illite-hosted pores. Meanwhile, other shale constituents (including kaolinite, chlorite, and OM) that possess few pores can significantly increase the pore structure complexity by way of pore-blocking. [ABSTRACT FROM AUTHOR]

A joint-processing model for multi-GNSS (GPS, GLONASS, BDS and GALILEO) precise point positioning (PPP) is proposed, in which raw code and phase observations are used. In the proposed model, inter-system biases (ISBs) and GLONASS code inter-frequency biases (IFBs) are carefully considered, among which GLONASS code IFBs are modeled as a linear function of frequency numbers. To get the full rank function model, the unknowns are re-parameterized and the estimable slant ionospheric delays and ISBs/IFBs are derived and estimated simultaneously. One month of data in April, 2015 from 32 stations of the International GNSS Service (IGS) Multi-GNSS Experiment (MGEX) tracking network have been used to validate the proposed model. Preliminary results show that RMS values of the positioning errors (with respect to external double-difference solutions) for static/kinematic solutions (four systems) are 6.2 mm/2.1 cm (north), 6.0 mm/2.2 cm (east) and 9.3 mm/4.9 cm (up). One-day stabilities of the estimated ISBs described by STD values are 0.36 and 0.38 ns, for GLONASS and BDS, respectively. Significant ISB jumps are identified between adjacent days for all stations, which are caused by the different satellite clock datums in different days and for different systems. Unlike ISBs, the estimated GLONASS code IFBs are quite stable for all stations, with an average STD of 0.04 ns over a month. Single-difference experiment of short baseline shows that PPP ionospheric delays are more precise than traditional leveling ionospheric delays. [ABSTRACT FROM AUTHOR]

Purpose To investigate oncogenic platelet-derived growth factor receptor(PDGFR) fusion genes involvement in hematological malignancies, the advances in the PDGFR fusion genes diagnosis and development of PDGFR fusions inhibitors. Methods Literature search was done using terms “PDGFR and Fusion” or “PDGFR and Myeloid neoplasm” or ‘PDGFR and Lymphoid neoplasm’ or “PDGFR Fusion Diagnosis” or “PDGFR Fusion Targets” in databases including PubMed, ASCO.org, and Medscape. Results Out of the 36 fusions detected, ETV6(TEL)-PDGFRB and FIP1L1-PDGFRA fusions were frequently detected, 33 are as a result of chromosomal translocation, FIP1L1-PDGFRA and EBF1-PDGFRB are the result of chromosomal deletion and CDK5RAP2- PDGFRΑ is the result of chromosomal insertion. Seven of the 34 rare fusions have detectable reciprocals. Conclusion RNA aptamers are promising therapeutic target of PDGFRs and diagnostic tools of PDGFRs fusion genes. Also, PDGFRs have variable prospective therapeutic strategies including small molecules, RNA aptamers, and interference therapeutics as well as development of adaptor protein Lnk mimetic drugs. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) remains one of the most metastasizing tumors, and directional cell migration is critical for targeting tumor metastasis. GIT2 has been known to bind to Paxillin to control cell polarization and directional migration. However, the molecular mechanisms underlying roles of GIT2 in controlling cell polarization and directional migration remain elusive. Here we demonstrated GIT2 control cell polarization and direction dependent on the regulation of Golgi through RUSC2. RUSC2 interacts with SHD of GIT2 in various lung cancer cells, and stabilizes GIT2 (Mazaki et al., 2006; Yu et al., 2009) by decreasing degradation and increasing its phosphorylation. Silencing of RUSC2 showed reduced stability of GIT2, defective Golgi reorientation toward the wound edge and decreased directional migration. Moreover, short-term EGF stimulation can increase the interaction between RUSC2 and GIT2, prolonged stimulation leads to a decrease of their interaction through activating Rab35. Silencing of Rab35 also reduced stability and phosphorylation of GIT2 and decreased cell migration. Taken together, our study indicated that RUSC2 participates in EGFR signaling and regulates lung cancer progression, and may be a new therapeutic target against lung cancer metastasis. [ABSTRACT FROM AUTHOR]

The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) play a key role in signaling pathways in oncogenesis. The overexpression of PDGFs and PDGFRs and the oncogenic alterations of these receptors have been implicated in human cancers and correlated significantly with poor outcomes. This review discusses the biology of the PDGF isoforms and receptors briefly, and their role in oncogenesis. Also, the attractiveness of targeting PDGFs and PDGFRs, based on a wide display of oncologic alterations in cancers, diverse therapeutic strategies, their roles in resistance to cancer treatments with prospects of overcoming drug resistance, and the extent to which validated biomarkers have been developed for effective PDGFs and PDGFRs-based cancer management are discussed. [ABSTRACT FROM AUTHOR]

PKG II, cGMP-dependent protein kinase type II; EGF, epidermal growth factor; Ad-LacZ, adenoviral vector containing the -galactosidase gene; Ad-PKG II, adenoviral vector containing the PKG II gene; cGMP, cyclic guanosine monophosphate. PKG II, cGMP-dependent protein kinase type II; Ad-LacZ, adenoviral vector containing the -galactosidase gene; Ad-PKG II, adenoviral vector containing the PKG II gene; 8-pCPT-cGMP, 8-(4-chlorophenylthio)-cGMP; cGMP, cyclic guanosine monophosphate; EGF, epidermal growth factor. [Extracted from the article]

• The inappropriate method of separating pseudorange bias into a purely receiver-dependent part or purely satellite-dependent part in mixed network is proved. • A simplified algorithm of the clock offset estimation with pseudorange bias correction is derived. • The pseudorange bias is used to improve the accuracy and performance of precise point position. The pseudorange bias inconsistencies are notably originating primarily from the individual chip shape distortions in the ranging signals, these distortions cause different shifts of the correlator's tracking point for receivers, as a result giving rise to a different pseudorange bias for each pseudorange observation. The different bias should be properly dealt with in the process of satellite clock offset estimation when receivers of mixed types are used. In this work, using observations from 140 international global navigation satellite system (GNSS) service stations, the pseudorange bias was calculated, and the effect of inconsistent biases on satellite clock offset estimation from different receiver networks was investigated. The inconsistencies between the GPS satellites were ranging from −6 ns to 4 ns. For GALILEO and BDS, the biases are significant, ranging from −20 ns to 40 ns and −60 ns to 40 ns, respectively. The biases of the individual satellites are receiver-related and statistically stable from day to day. The influence of pseudorange bias was strikingly noticeable, and can improve the accuracy of the estimated clock offset by several ps for GPS; and by more than 15 ps for GALILEO and BDS after considering bias inconsistencies. Furthermore, owing to the pseudorange bias correction, the convergence and positioning performance have improved significantly, with an improvement of more than 12 % for the static precise point position (PPP), and more than 10 % for the kinematic PPP. [ABSTRACT FROM AUTHOR]

Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which feature extremely dynamic imaging appearance, brain shape and size. However, for non-human primates, which are highly valuable animal models for understanding human brains, the existing brain atlases are mainly developed based on adults or adolescents, denoting a notable lack of temporally densely-sampled atlases covering the dynamic early brain development. To fill this critical gap, in this paper, we construct a comprehensive set of longitudinal brain atlases and associated tissue probability maps (gray matter, white matter, and cerebrospinal fluid) with totally 12 time-points from birth to 4 years of age (i.e., 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 months of age) based on 175 longitudinal structural MRI scans from 39 typically-developing cynomolgus macaques, by leveraging state-of-the-art computational techniques tailored for early developing brains. Furthermore, to facilitate region-based analysis using our atlases, we also provide two popular hierarchy parcellations, i.e., cortical hierarchy maps (6 levels) and subcortical hierarchy maps (6 levels), on our longitudinal macaque brain atlases. These early developing atlases, which have the densest time-points during infancy (to the best of our knowledge), will greatly facilitate the studies of macaque brain development. [ABSTRACT FROM AUTHOR]

Summary: Monkeys serve as important model species for studying human diseases and developing therapeutic strategies, yet the application of monkeys in biomedical researches has been significantly hindered by the difficulties in producing animals genetically modified at the desired target sites. Here, we first applied the CRISPR/Cas9 system, a versatile tool for editing the genes of different organisms, to target monkey genomes. By coinjection of Cas9 mRNA and sgRNAs into one-cell-stage embryos, we successfully achieve precise gene targeting in cynomolgus monkeys. We also show that this system enables simultaneous disruption of two target genes (Ppar-γ and Rag1) in one step, and no off-target mutagenesis was detected by comprehensive analysis. Thus, coinjection of one-cell-stage embryos with Cas9 mRNA and sgRNAs is an efficient and reliable approach for gene-modified cynomolgus monkey generation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Both the morphology and composition of PdAg surfaces are considered in this study. [•] The d-electron activities of Pd atoms are compared among these three surfaces. [•] The close-packed surface alloy is not better than less-densely packed surfaces. [•] The (100) surface activity remains well when the surface Ag concentration grows. [Copyright &y& Elsevier]

Abstract: The small GTPases regulate many major biological processes in both tumorigenesis and tumor progression such as cell survival, actin cytoskeleton organization, cell polarity and movement. Wnt5a, a non-canonical Wnt family member, is implicated in the activation of small GTPases in breast cancer. We previously demonstrated that Wnt5a signaling stimulates the migration of breast cancer cells MDA-MB-231 via activating RhoA. However, we found here that RhoA activation was not enhanced by Wnt5a in breast cancer cells MCF-7. The conflicting results prompted us to further probe novel small GTPases in response to Wnt5a and investigate the mechanisms whereby cell migration is regulated. We showed here that Wnt5a dose dependently activated Dvl2, Rab35 and Rac1 and subsequently promoted the migration of MCF-7 cells, which was, however, abolished by knocking down Wnt5a expression via small interfering RNA (siRNA) transfection. Dvl2 siRNA significantly decreased background and Wnt5a-induced Rab35/Rac1 activation and, consequently, cell migration. Rab35 short hairpin RNA (shRNA) remarkably inhibited background and Wnt5a-induced Rac1 activation and cell migration. Additionally, blockade of Rac1 activation with Rac1 siRNA suppressed background and Wnt5a-induced cell migration. Co-immunoprecipitation and immunofluorescence assays showed that Dvl2 bound to Rab35 in mammalian cells. Taken together, we demonstrated that Wnt5a promotes breast cancer cell migration via the Dvl2/Rab35/Rac1 signaling pathway. These findings implicate Wnt5a signaling in regulating small GTPases, which could be targeted for manipulating breast cancer cell migration. [Copyright &y& Elsevier]

Abstract: Wnt5a, a non-transforming Wnt family member, plays complicated roles in oncogenesis and cancer metastasis. However, Wnt5a signaling in gastric cancer progression remains poorly defined. In this study, we found that Wnt5a dose-dependently stimulated the migration of human gastric cancer cells (SGC-7901), with the maximal effect at 100ng/mL, via enhancing phosphorylation of PI3K/Akt and GSK3β and activating RhoA. Pharmaceutical inhibition of PI3K with LY294002 or Akt siRNA significantly decreased Wnt5a-induced GSK3β phosphorylation and consequently cell migration. Additionally, GSK3β siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Analogously, pre-treatment with LiCl, which induced phosphorylation of GSK3β at Ser9, increased Wnt5a-induced cell migration. Finally, ectopic expression of dominant negative RhoA (N19) suppressed Wnt5a-induced cell migration. Taken together, we demonstrated for the first time that Wnt5a promoted gastric cancer cell migration via the PI3K/Akt/GSK3β/RhoA signaling pathway. These findings could provide a rationale for designing new therapy targeting gastric cancer metastasis. [Copyright &y& Elsevier]

Abstract: A density functional theory (DFT) method has been applied to study the adsorption of thiophenic compounds such as thiophene (TP), benzothiophene (BT), dibenzothiophene (DBT) on cation-exchanged Cu(I)Y, Ni(II)Y, Ce(III)Y zeolites. All of calculations were carried out by the generalized gradient approximation (GGA) with the BLYP exchange-correlation functional and DNP basis set. The calculated results indicate that the stable adsorption configuration of TP molecule adsorbed on the Cu(I)Y is the η5 adsorption mode, whereas for BT and DBT, the η1S adsorption mode was found for the both molecules. Only the η1S adsorption mode can be obtained for the three thiophenic compounds adsorbed on the Ni(II)Y. The η5 adsorption mode can be ascribed to the adsorption of thiophene molecules on the Ce(III)Y, but the competition of different adsorption modes could possibly occur during the adsorption process of BT and DBT on the Ce(III)Y. Moreover, the selectivity of TP adsorbed on the adsorbents is in the order of Cu(I)Y>Ce(III)Y>Ni(II)Y, while for BT and DBT, the order is Cu(I)Y>Ni(II)Y>Ce(III)Y. [Copyright &y& Elsevier]

Abstract: Mesenchymal stem cells (MSCs) are known as a population of multi-potential cells able to proliferate and differentiate into multiple mesodermal tissues including bone, cartilage, muscle, ligament, tendon, fat and stroma. In this study human MSCs were successfully isolated from the umbilical cords. The research characteristics of these cells, e.g., morphologic appearance, surface antigens, growth curve, cytogenetic features, cell cycle, differentiation potential and gene expression were investigated. After 2weeks of incubation, fibroblast-like cells appeared to be dominant. During the second passage the cells presented a homogeneous population of spindle fibroblast-like cells. After more than 4months (approximately 26 passages), the cells continued to retain their characteristics. Flow cytometry analysis revealed that CD29, CD44, CD95, CD105 and HLA-I were expressed on the cell surface, but there was no expression of hematopoietic lineage markers, such as CD34, CD38, CD71 and HLA-DR. Chromosomal analysis showed the cells kept a normal karyotype. The cell cycle at the third passage showed the percentage of G0/G1, G2/M and S phase were 88.86%, 5.69% and 5.45%, respectively. The assays in vitro demonstrated the cells exhibited multi-potential differentiation into osteogenic and adipogenic cells. Both BMI-1 and nucleostemin genes, expressed in adult MSCs from bone marrow, were also expressed in umbilical cord MSCs. Here we show that umbilical cords may be a novel alternative source of human MSCs for experimental and clinical applications. [Copyright &y& Elsevier]

Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical application because of their potential use in regenerative medicine and tissue engineering. However, the therapeutic application of MSCs still remain limited unless the favorable effect of MSCs for tumor growth in vivo and the long-term safety of the clinical applications of MSCs are better understood. In this study, MSCs derived from fetal bone marrow (FMSCs) and adult MSCs (AMSCs) alone or FMSCs and AMSCs with tumor cell line (F6 or SW480) together were transplanted subcutaneously into BALB/c-nu/nu mice to observe the outgrowth of tumor, and the characteristics of tumor cells were investigated by pathological and immunohistochemical methods, flow cytometry and real-time quantitative PCR. The results showed that both FMSCs and AMSCs could favor tumor growth in vivo. The pathologic examination revealed that tumor tissues had rich vessel distribution, extensive necrosis and invasion surrounding normal tissues, such as muscular tissue and subcutaneous tissue. In the immunohistochemical examination, tumor cells mixed with MSCs transplanted subcutaneously exhibited elevated capability of proliferation, rich angiogenesis in tumor tissues and highly metastatic ability. To understand whether MSCs affected the general properties of the tumor cells in vivo, the expression of some surface antigens and Bmi-1 gene of tumor tissue cells was detected in this study. The results indicated that these parameters were not affected after the interaction of MSCs with tumor cells in vivo. These findings suggested that MSCs could favor tumor growth in vivo. It is necessary to carry out a study for assurance of the long-term safety before MSCs were used as a therapy tools in regenerative medicine and tissue engineering. [Copyright &y& Elsevier]