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As the number of cores in a chip multiprocessor increase, the directory size becomes excessive. Current research shows that directory size can be reduced by tracking private entries with coarse-grain directory entries called region entries. In order to indicate which blocks the region owner has cached, the present vector in the region entries in the dual-grain directory (DGD) uses a bit vector format. If a coarser-grain region granularity is used, the length of the region entries becomes excessive. Besides, most of the latest scalable directories use the short-entry directory format with only one pointer. Therefore, DGD has limited flexibility of region granularity and is incompatible with the latest scalable directories. In this paper, we propose a scalable short-entry dual-grain coherence directory with flexible region granularity (SS-DGD). In private region entries, a counter is used instead of the original bit vector. Region entries using counters and private block entries using a single pointer always have the same length, giving SS-DGD the flexibility of region size. To reduce the directory size, SS-DGD is divided into a shared directory and a private directory that includes private block entries and private region entries. With the same total number of directory entries, SS-DGD has a smaller directory size than previous DGD because the private directory entries in SS-DGD are shorter. And the detailed simulation-based study shows that there are no statistically significant differences in execution time and network traffic between SS-DGD and DGD. In the 64-core system, our proposal can reduce the directory size by 29.9%. More importantly, the region entries in SS-DGD can be used in the latest scalable directories and have a high potential to compress the number of directory entries. [ABSTRACT FROM AUTHOR]

Studies on the environmental fate and risk of mercury (Hg) have been mostly focused on total mercury and a very toxic species methylmercury (MeHg). However, another organic Hg species, ethylmercury (EtHg), has long been neglected, partly due to the analytical limitations. The generally used aqueous ethylation for analyzing MeHg converts both Hg2+ and EtHg into diethylmercury, making it impossible to distinguish EtHg from Hg2+. Thanks to the emerging methods other than ethylation derivatization, EtHg has been identified in soils and sediments from a variety of sites, with a similar concentration to MeHg in some cases (e.g., the Florida Everglades). More importantly, results from recent studies also suggested that EtHg in the environment is derived not only from anthropogenic input (as bactericide, etc.), but also possibly from unknown natural formation pathways. Unfortunately, the environmental aspects, including formation, transport, transformation, bioaccumulation, and toxicity of EtHg, are still not well understood, limiting our understanding of this "new" organic Hg species. In this review, the current analytical methods focusing on gas/liquid chromatography coupled with atomic spectrometer for EtHg are summarized. Then, the occurrence of EtHg and its possible natural sources in the environment are discussed. Finally, the environmental transport, degradation, bioaccumulation, and toxicity of EtHg are discussed. It is expected that this review would provide comprehensive background and important clues to understand the natural occurrence and fate of EtHg. [ABSTRACT FROM AUTHOR]

The incidence and mortality rate of gastric cancer (GC) have remained high worldwide. Although some progress has been made in immunotargeted therapy, the treatment effect remains limited. With more attention has been paid to the immune potential of tumor-associated macrophages (TAMs), but the specific mechanisms of tumor immunity are still unclear. Thus, we screened marker genes in TAMs differentiation (MDMs) through single-cell RNA sequencing, and combined with GC transcriptome data from TCGA and GEO databases, the clinical and TME characteristics, prognostic differences, immune infiltration, and drug sensitivity among different subtypes of patients with GC in different data sets were analyzed. A prognostic model of GC was constructed to evaluate the prognosis and immunotherapy response of patients with GC. In this study, we extensively studied the mutations in MDMs such as CGN, S100A6, and C1QA, and found differences in the infiltration of immune cells and immune checkpoints including M2 TAMs, T cells, CD274, and CTLA4 in different GC subtypes. In the model, we constructed a predictive scoring system with high accuracy and screened out key MDMs-related genes associated with prognosis and M2 TAMs, among which VKORC1 may be involved in GC progression and iron death in tumor cells. Therefore, this study explores the therapeutic strategy of TAMs reprogramming in-depth, providing new ideas for the clinical diagnosis, treatment, and prognosis assessment of GC. [ABSTRACT FROM AUTHOR]

Knowledge of x-ray free electron lasers' (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs' self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator's configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties. Methods to characterize the free-electron laser pulses are evolving and their performances are also improving. Here the authors demonstrate a method based on the artificial neural networks to predict the output pulses of the X-ray free-electron laser by considering the electron beam parameters as input. [ABSTRACT FROM AUTHOR]

Drug resistance is a major obstacle leading to treating failure and poor outcome in gastric cancer (GC). This study explores the interaction between SMAD family member 1 (SMAD1) and Yes1-associated transcriptional regulator (YAP1) and their roles in cisplatin (DDP) resistance in GC. Transcriptome analysis predicted that SMAD1 is highly expressed in DDP-resistant cells. Elevated SMAD1 expression was detected in GC tissue and cells, especially in DDP-resistant cells (MKN-45/DDP and AGS/DDP). SMAD1 downregulation in cells decreased 50% inhibition value of DDP, reduced proliferation, migration, and invasion, and promoted cell cycle arrest and apoptosis. A protein–protein interaction network suggested a possible SMAD1 and YAP1 interaction in GC. The SMAD1 and YAP1 interaction was validated by chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), and luciferase assays. SMAD1 bound to YAP1 and activated its transcription. SMAD1 formed complexes with YAP1 in nucleus, and YAP1 upregulation enhanced SMAD1 activity as well. Upregulation of YAP1 restored the malignant behaviors of GC cells suppressed by SMAD1 silencing. In vivo, SMAD1 silencing suppressed growth and DDP resistance of xenograft tumors in nude mice, and this suppression was blocked by YAP1 overexpression again. In conclusion, this study demonstrates that SMAD1 can interact with YAP1 to enhance the DDP resistance of GC cells. [ABSTRACT FROM AUTHOR]

Although the stick-slip piezoelectric actuator has been extensively developed, its consistency in forward and reverse motions is still poor under the same driving voltage and frequency. To improve the consistency in forward and reverse motion, extremely precise adjustment of actuators is necessary. For achieving high consistency in forward and reverse motions with low difficulty in assembly and adjustment, a stick-slip piezoelectric actuator with the symmetric mechanism and optimized installation method was developed in this study. By means of the pseudo-rigid body method (PRBM), matrix-based compliance modeling (MCM) method and the finite element method (FEM), theoretical calculation and analysis of the designed symmetric flexure hinge mechanism (SFHM) were carried out firstly. Then, the effects of installation methods on the forward and reverse motion consistency were investigated by experiments, and accordingly, an optimized installation method was determined. With this method, output performances of the actuator were tested under various voltages, frequencies and external loads, and the consistency in forward and reverse motions were further compared and analyzed. The experimental results indicated that good consistency in forward and reverse motions had been successfully achieved by the symmetric mechanism and optimized installation method, and the ratio of difference λ was only 6.80% which showed the actuator had an extremely competitiveness. High bidirectional motion consistency will reduce the control difficulty of the actuator, which is beneficial to its application in the fields of precision instruments, aerospace and material mechanical performance testing. [ABSTRACT FROM AUTHOR]

Coagulation is a simple and cost-effective water treatment method that does not work well in removing multiple cationic and anionic heavy metals simultaneously from drinking water. Titanium potassium oxalate (K2TiO(C2O4)2), a fur tanning reagent, was found to be able to efficiently remove arsenite (As(III)), arsenate (As(V)), and Cd simultaneously. A dose of 120 µmol/L K2TiO(C2O4)2 could remove more than 90% of As and Cd to meet the drinking water standards when their initial concentrations were 10 times their maximum concentration limits, whereas traditional coagulants, such as Fe2(SO4)3 and Al2(SO4)3, failed to meet the drinking water standards. Additionally, K2TiO(C2O4)2 coagulation consumes natural water hardness (Ca2+/Mg2+) to produce softer water and releases healthy K+ as a by-product. The mechanism study indicated that K2TiO(C2O4)2 reacted with natural calcium ions in drinking water to form calcium oxalate, while residual titanium was hydrolyzed with water to form hydrous titanium oxide. Arsenic was removed primarily via complexation with hydrous titanium oxide, while Cd was removed via the combined effect of adsorption by hydrous titanium oxide and mixed-crystal formation by calcium oxalate. This study provides an efficient coagulant for removing multiple heavy metals simultaneously, which can be applied in water treatment to provide safe and healthy drinking water. [ABSTRACT FROM AUTHOR]

Diffuse gliomas (DGs) are the most common and lethal primary neoplasms in the central nervous system. The latest 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was published in 2021, immensely changing the approach to diagnosis and decision making. As a part of the Chinese Glioma Genome Atlas (CGGA) project, our aim was to provide genomic profiling of gliomas in a Chinese cohort. Two hundred eighty six gliomas with different grades were collected over the last decade. Using the Illumina HiSeq platform, over 75.8 million high-quality 150 bp paired-end reads were generated per sample, yielding a total of 43.4 billion reads. We also collected each patient's clinical and pathological information and used it to annotate their genetic data. All patients were diagnosed and classified by neuro-pathologist under the 2021 WHO classification. This dataset provides an important reference for researchers and will significantly advance our understanding of gliomas. Measurement(s) glioma Technology Type(s) Whole Exome Sequencing Sample Characteristic - Organism Homo sapiens [ABSTRACT FROM AUTHOR]

The self-assembly of surface-order structures based on the surface wrinkling of stiff film-compliant substrate structures (SFCS) is potentially useful in the fabrication of functional devices, the manufacture of superhydrophobic or self-cleaning surfaces, and so on. Due to the influence of the intrinsic characteristic length (g), the surface wrinkling behavior of SFCS at the micro scale is different from that at the macro scale. In this work, based on the strain gradient theory, a trans-scale surface wrinkling model for SFCS is established. First, the effectiveness of this model is verified by previous experiments. Then, based on the model and dimensional analysis, the effect of g on the surface wrinkling behavior is investigated, and the scaling relationship of surface wrinkling of SFCS at different scales is analyzed. The results show that the influence of g cannot be neglected when the film thickness decreases to the one comparable to g. At the micro scale, g will lead to the increase of the critical wrinkling wavelength and load. In addition, the scaling relationship of surface wrinkling at the micro scale will not follow the traditional one. Our study explains the underlying mechanism of the dissimilarity of surface wrinkling behaviors of SFCS at different scales and lays a theoretical foundation for the precise control of surface-order structures. [ABSTRACT FROM AUTHOR]

Air leakage in borehole not only seriously restricts the development and utilization of coal bed methane (CBM) but also affects gas disaster prevention and underground safety mining. Several triaxial-seepage experiments were conducted to analyze the seepage characteristic change of raw coal under different loads in consideration of the above-mentioned problems. On this basis, a dynamic multifield coupling model, including coal permeability evolution, creep mechanical, and binary gas flow system, was proposed to describe the CBM drainage process. Based on this fully coupling model, factors influencing air leakage flux were investigated by numerical method. Findings show that the dynamic change of air leakage flux is determined by stress and permeability variation. Therefore, in practical work, grouting method can be adopted to decrease coal permeability and softening modulus as well as increase coal residual strength and support stress, so as to reduce air leaking in borehole. Furthermore, we also proposed a new remedy method, including self-developed GP material and corresponding sealing–plugging integrative device, for preventing borehole leakage. The field test results indicate that the gas concentration of the boreholes was effectively enhanced after the leakage treatment by this method, and a great drainage level was still maintained at the late period. The results in this work can provide a remedy method for improving borehole sealing and drained gas quality. Such method is important for enhancing the CBM utilization, reducing greenhouse gas emission, and ensuring mining safety. [ABSTRACT FROM AUTHOR]

The hard film/soft substrate systems are widely found in production and life. In order to better understand the indentation response of those systems, a closed-form indentation model is established based on the theory of plates and the assumption of Hertz contact stress distribution. Inspired by the model, a new method of measuring the mechanical properties of nanofilms by indentation on hard film/soft substrate system is proposed. Then, with the help of finite element method (FEM), the effectiveness of the model and the method is systematically verified. The results show that compared with the Xu-Pharr model which established by the perturbation method, our model can better describe the compliance of the hard film/soft substrate system in a lager range of modulus ratio of the film to the substrate. In order to obtain the modulus of the nanofilms more accurately by our method, the optimum indentation depth for testing is 0.5 times the film thickness to 1 times the film thickness, and it is best to use a softer substrate to make the modulus ratio of the film to the substrate greater than 103. In addition, the radius of the AFM tip is preferably more than 1 times the film thickness and less than 4 times the film thickness, and a smooth surface of the sample is most preferred. Compared with free standing indentation test or bulge test, our research provides a more convenient and cheaper method for measuring the nanofilms' modulus in laboratory. [ABSTRACT FROM AUTHOR]

Purpose: To explore the characteristics of growth disturbance in patients with intracranial germinoma with different origins. Methods: Clinical data of 151 patients with single-origin germinomas were studied retrospectively. Z-score of height (ZSOH) at both diagnosis and the last follow-up was calculated using the WHO AnthroPlus software. Linear regression was used to analyse the correlation between the absolute change in ZSOH (|ZSOH last follow-up - ZSOH diagnosis|) and clinical factors. Results: The mean ZSOH decreased significantly in every origin subgroup at the last follow-up. In patients with sellar germinoma (n = 62), the mean ZSOH values at both diagnosis and the last follow-up were significantly lower than those in patients with pineal (n = 30) (p < 0.001) or basal ganglia germinomas (n = 59) (p < 0.001), respectively. In patients with basal ganglia germinoma, the mean absolute change in ZSOH decreased significantly compared to that in the patients with sellar (p = 0.006) or pineal germinomas (p = 0.04). Linear analysis revealed that sex (male vs female; p = 0.003) and age at diagnosis (≤10 years vs >10 years; p = 0.026) had negative correlations, while radiation dose at the hypothalamic-pituitary axis (HPA) (≤40 Gy vs >40 Gy; p = 0.085) had a marginally positive correlation, with absolute change in ZSOH. Conclusions: Patients with germinoma experienced growth retardation after treatments. The growth disturbance was consistent and more severe in patients with germinoma of sellar origin, while the greatest aggravation was observed in patients with germinoma of basal ganglia origin. Decreasing radiation dose to the HPA may minimize the negative impact of radiotherapy on growth. [ABSTRACT FROM AUTHOR]

Dynamic Adaptive Streaming over Http (DASH) -based video streaming applications are becoming increasingly prevalent over the mobile Internet. Many efforts have been made to optimize their performances. Multipath video streaming that simultaneously utilizes multiple wireless networks for video content delivery is a common method. Another effective approach is the cross-layer video streaming optimization that jointly takes the parameters at different protocol layers into account. However, multipath streaming schemes mainly focus on how to efficiently utilize multiple wireless networks and the collaboration of parameters at different layers in each network is neglected. Likewise, the cross-layer schemes normally optimize the parameters at different layers in purely one network without fully utilizing the aggregated bandwidths of multiple available wireless networks. Therefore, both of them are sub-optimal and might suffer from degrading performance. In this paper, we propose a joint Cross-layer DASH-based multipath video streaming scheme that takes advantage of bandwidth aggregation of multiple wireless networks and further improves the performance by optimizing the different layers' parameters in each network with a cross-layer manner. In the proposed scheme, the LTE and 802.11ac networks are adopted. The bitrate of DASH-based video chunk at application layer, the rate allocation among networks and the Modulation and Coding Scheme (MCS) at physical layers in LTE and 802.11ac downlink are jointly optimized. We also compare our proposed scheme to state-of-the-art schemes using trace-driven experiments. Experimental results show that our proposed scheme outperforms state-of-the-art schemes in terms of PSNR, normalized QoE, and balance between video bitrate and rebuffering penalty. [ABSTRACT FROM AUTHOR]

The 2019 Coronavirus Disease (COVID-19) has become an unprecedented public crisis. We retrospectively investigated the clinical data of 197 COVID-19 patients and identified 88 patients as disease aggravation cases. Compared with patients without disease aggravation, the aggravation cases had more comorbidities, including hypertension (25.9%) and diabetes (20.8%), and presented with dyspnoea (23.4%), neutrophilia (31.5%), and lymphocytopenia (46.7%). These patients were more prone to develop organ damage in liver, kidney, and heart (P < 0.05). A multivariable regression analysis showed that advanced age, comorbidities, dyspnea, lymphopenia, and elevated levels of Fbg, CTnI, IL-6, and serum ferritin were significant predictors of disease aggravation. Further, we performed a Kaplan–Meier analysis to evaluate the prognosis of COVID-19 patients, which suggested that 64.9% of the patients had not experienced ICU transfers and survival from the hospital. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) has a strong application potential as a lightweight metal. Yet, its absolute strength still needs improvement. In this work, we demonstrate that machine learning can be utilized to guide the development of high-strength Mg cast alloys. In the design framework, the composition and heat treatment condition are iteratively optimized by a surrogate model that is also evolving. After two iterations, a new alloy with the composition of Mg-10.0Al-2.0Sn-2.0Zn-0.1Ca-0.1Mn (at. pct) was identified. After aging at 200 °C for 96 hours, this alloy shows a Vickers hardness value of 110.5 Hv, which surpasses the highest value (102.5 Hv) in the initial dataset from literature. Finally, microstructure of the optimized alloy was characterized to understand the origin of its high hardness. This work demonstrates the potential of data-driven approaches for material development. [ABSTRACT FROM AUTHOR]

Vehicle-infrastructure cooperative systems can potentially enhance both traffic safety and efficiency by conducting coordinated control through the interactive strategy between the vehicles and the infrastructure. In this study, the interactive strategy of a vehicle infrastructure cooperative system is designed. Lane change maneuver is a conventional behavior in driving. Thus, this paper proposes a trajectory planning algorithm based on a Gauss pseudo-spectral method that is applied to the intelligent vehicle-infrastructure cooperative system in the lane change scenario. A road side unit calculates the planning trajectory using collected vehicle information and sensor data and then sends the trajectory planning advice to the designated vehicle. The Gauss pseudo-spectral method is used to obtain the planning trajectory, which effectively helps solve the discontinuous optimization problems in partial conditions. It transforms the optimal control problem of dynamic systems into a nonlinear programming problem using the orthogonal collocation method to discretize the objective function and various constraints of the optimization problem. Furthermore, the ssuential quadratic programming method is used to solve the problem numerically. The effectiveness of the proposed method and interactive strategy are demonstrated through simulations and experimental results. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary intracranial tumor and is associated with very low survival rates. The development of reliable biomarkers can help to elucidate the molecular mechanisms involved in glioma development. Here the expression of ABCC8 mRNA, clinical characteristics, and survival information based on 1893 glioma samples from four independent databases were analyzed. The expression patterns of ABCC8 mRNA were compared by a Chi square test. The overall survival rate of gliomas was evaluated according to the expression level of ABCC8 mRNA. The prognostic value of this marker in gliomas was tested using Cox single factor and multi factor regression analyses. We found patients with low WHO grade, oligodendrocytoma, low molecular grade, IDH mutation, and 1p19q combined deletion had high ABCC8 mRNA expression. The patients with high expression of ABCC8 mRNA had longer survival. ABCC8 mRNA expression was a new independent prognostic index for glioma. Temozolomide chemotherapy was an independent index to prolong overall survival in high ABCC8 mRNA expression glioma patients, whereas in patients with low expression, there was no significant difference. So ABCC8 mRNA expression could be an independent prognostic indicator for glioma patients and could predict the sensitivity of glioma to temozolomide. [ABSTRACT FROM AUTHOR]

The indentation technique is widely used in measuring the mechanical properties of soft matter at the microscale or nanoscale, but still faces challenges by these unique properties as well as the consequent strong surface adhesion, including the strong nonlinear effect, unclear judgment of the contact point, difficulties in estimating the contact area, and the risk of the indenter piercing the sample. Here we propose a two-step method to solve these problems: lay a hard film on a soft matter, and obtain the viscoelastic properties of this soft matter through the indentation response of this composite structure. We first establish a theoretical indentation model of the hard film-soft substrate system based on the theory of plates, elastic-viscoelastic correspondence principle and Boltzmann superposition principle. To verify the correctness of this method, we measure the mechanical properties of the methyl vinyl silicone rubber (MVSR) covered by a Cu nanofilm. Finally, we test the effectiveness and error sensitivity of this method with the finite element method (FEM). The results show that our method can accurately measure the mechanical properties of soft matter, while effectively circumventing the problems of the traditional indentation technique. [ABSTRACT FROM AUTHOR]

As a theoretical basis, methane diffusion from coal particles can be used to determine the coalbed gas content, gas desorption index by drill cuttings of coal, evaluation parameters of coal gas mining, and the gas outburst prediction. Moisture content is one of the significant factors influencing the diffusion law of gas-bearing coal particles. In this paper, three deformed coal samples with diverse metamorphic degrees, taken from three different coal mines with coal and gas outburst hazard, were investigated through the self-made devices. The variation law of diffusion flux, diffusion coefficient, and diffusion speed with moisture content was experimentally studied. The results show that diffusion flux, diffusion speed, and diffusion coefficients of high-, medium-, and low-rank coal samples decrease significantly with the increasing moisture content until they reach equilibrium moisture content. The diffusion coefficient of dry coal particles is 3–5 times larger than that of coal particles with equilibrium moisture at the same metamorphic degree. The diffusion coefficient of coal samples at different ranks decreases with time and ranges from 1.58E-08 to 3.03E-07 cm2/s. Based on gas migration theory in porous media and experimental results, the influence mechanism of moisture on gas diffusion rules was discussed. [ABSTRACT FROM AUTHOR]

Purpose: Primary glioblastoma (pGBM) is the most common and lethal type of neoplasms in the central nervous system, while the existing biomarkers, lacking consideration on the stemness changes of GBM cells, are not specific enough to predict the complex prognosis respectively. We aimed to build a high-efficiency prediction gene signature related to GBM cell stemness and investigate its prognostic value in primary glioblastoma.Methods: Differentially expressed genes were screened in GSE23806 database. The selected genes were then verified by univariate Cox regression in 591 patients from four enormous independent databases, including the Chinese Glioma Genome Atlas (CGGA), TCGA, REMBRANDT and GSE16011. Finally, the intersected genes were included to build the gene signature. GO analysis and GSEA were carried out to explore the bioinformatic implication.Results: The novel five-gene signature was used to identify high- and low-risk groups in the four databases, and the high-risk group showed notably poorer prognosis (P < 0.05). Gene ontology (GO) terms including “immune response”, “apoptotic process”, and “angiogenesis” were picked out by GO analysis and GSEA, which revealed that the gene signature was highly possibly related to the stemness of GSCs and predicting the prognosis of GBM effectively.Conclusion: We built a gene signature with five glioblastoma stem-like cell (GSC) relevant genes, and predicted the survival in four independent databases effectively, which is possibly related to the stemness of GSCs in pGBM. Several GO terms were investigated to be correlated to the signature. The signature can predict the prognosis of glioblastoma efficiently. [ABSTRACT FROM AUTHOR]

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan-Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan-Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma. [ABSTRACT FROM AUTHOR]

Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems. [ABSTRACT FROM AUTHOR]

In this article, the high codimension bifurcations of a six-neuron BAM neural network system with multiple delays are addressed. We first deduce the existence conditions under which the origin of the system is a Bogdanov-Takens singularity with multiplicities two or three. By choosing the connection coefficients as bifurcation parameters and using the formula derived from the normal form theory and the center manifold, the normal forms of Bogdanov-Takens and triple zero bifurcations are presented. Some numerical examples are shown to support our main results. [ABSTRACT FROM AUTHOR]

Recent researches have shown that the Structural SIMilariy (SSIM)-based Rate-Distortion Optimization (RDO) can obtain more structural information than the traditional SSE-based RDO for video coding. Correspondingly, the perceptual video quality is improved at certain degree for the video stream encoded by the SSIM-based RDO. However, for the MB with significant luminance change (due to the flashlight or sunshine change, etc.) but little structure change compared to the co-located MB in the referred frame, the SSIM-based RDO may select improper encoding mode (SKIP) which leads to uncomfortable visual experience. In this paper, involving the surrounding pixels of the current coding MB into the measurement of spacial texture quality degradation, the RDO which jointly considers the SSIM-based distortion and SSE-based distortion is proposed to improve H.264/AVC perceptual coding performance. The Lagrange multiplier in the proposed RDO is firstly derived at the frame level. Then, to make the Lagrange multiplier more adaptive to the specific video content, the Lagrange multiplier for each individual MB is refined based on the visual information theory. Experimental results show that the proposed perceptual RDO can select the optimal encoding mode which preserves as much structural information as possible with as little SSE-based distortion as possible, and that the perceptual quality of the encoded video is improved. [ABSTRACT FROM AUTHOR]

In the nervous system, Hes1 shows an oscillatory manner in neural progenitors but a persistent one in neurons. Many models involving Hes1 have been provided for the study of neural differentiation but few of them take the role of microRNA into account. It is known that a microRNA, miR-9, plays crucial roles in modulating Hes1 oscillations. However, the roles of miR-9 in controlling Hes1 oscillations and inducing transition between different cell fates still need to be further explored. Here we provide a mathematical model to show the interaction between miR-9 and Hes1, with the aim of understanding how the Hes1 oscillations are produced, how they are controlled, and further, how they are terminated. Based on the experimental findings, the model demonstrates the essential roles of Hes1 and miR-9 in regulating the dynamics of the system. In particular, the model suggests that the balance between miR-9 and Hes1 plays important roles in the choice between progenitor maintenance and neural differentiation. In addition, the synergistic (or antagonistic) effects of several important regulations are investigated so as to elucidate the effects of combinatorial regulation in neural decision-making. Our model provides a qualitative mechanism for understanding the process in neural fate decisions regulated by Hes1 and miR-9. [ABSTRACT FROM AUTHOR]

In this paper the Bogdanov-Takens (BT) bifurcation of an 2 m coupled neurons network model with multiple delays is studied, where one neuron is excitatory and the next is inhibitory. When the origin of the model has a double zero eigenvalue, by using center manifold reduction of delay differential equations (DDEs), the second-order and third-order universal unfoldings of the normal forms are deduced, respectively. Some bifurcation diagrams and numerical simulations are presented to verify our main results. [ABSTRACT FROM AUTHOR]

Chromosomal instability is a hallmark of human cancers and is closely linked to tumorigenesis. The prognostic value of molecular signatures of chromosomal instability (CIN) has been validated in various cancers. However, few studies have examined the relationship between CIN and glioma. Histone deacetylases (HDACs) regulate chromosome structure and are linked to the loss of genomic integrity in cancer cells. In this study, the prognostic value of HDAC4 expression and its association with markers of CIN were investigated by analyzing data from our own and four other large sample databases. The results showed that HDAC4 expression is downregulated in high- as compared to low-grade glioma and is associated with a favorable clinical outcome. HDAC4 expression and CIN were closely related in glioma from both functional and statistical standpoints. Moreover, the predictive value of the O- 6- methylguanine- DNA methyltransferase ( MGMT) promoter methylation status-a widely used glioma marker-was refined by HDAC4 expression level, which was significantly related to CIN in our study. In conclusion, we propose that HDAC4 expression, a prognostic and CIN marker, enhances the predictive value of MGMT promoter methylation status for identifying patients who will most benefit from radiochemotherapy. [ABSTRACT FROM AUTHOR]

The gene regulatory networks in which two lineage-affiliated transcription factors, such as GATA1 and PU.1, inhibit each other but activate themselves so as to regulate the choice between alternative cell fates have been extensively studied. These simple networks can generate bistability and explain the transitions between the alternative cell fates. The commitment of a progenitor cell to a new fate corresponds to the occurrence of different types of bifurcations, depending on if a system is symmetrical and how perturbations affect the system. Here we take a general modeling and analyzing approach and show that the lateral inhibition with symmetry and asymmetry can lead to different bifurcation dynamics. Especially, if cell fate decision-making is initiated with asymmetry or symmetry-breaking perturbations, a progenitor cell pre-patterns itself into a polarized cell, depending on the asymmetry or symmetry-breaking perturbations. This study may help us understand the fundamental features of binary cell fate decisions more clearly and further apply to a wider range of decision-making processes. [ABSTRACT FROM AUTHOR]

Cancer is the greatest challenge to human health in our era. Perturbations of receptor tyrosine kinase (RTK) function contribute to a large chunk of cancer etiology. Current evidence supports that mutations in RTKs mediate receptor dimerization and result in ligand-independent kinase activity and tumorigenesis, indicating that mutation-introduced receptor dimerization is a critical component of oncogenesis RTK mutations. However, there are no specialized reviews of this important principle. In the current review, we discuss the physiological and harmless RTK function and subsequently examine mutation-introduced dimerization of RTKs and the role of these mutations in tumorigenesis. We also summarize the protein structure characteristics that are important for dimerization and introduce research methods and tools to predict and validate the existence of oncogenic mutations introduced by dimerization in RTKs. [ABSTRACT FROM AUTHOR]

Promoter methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene has been considered as a prognostic maker and increasingly emphasized in the treatment of glioblastoma multiforme (GBM). Contrastingly, the correlation of MGMT with clinical outcomes in Chinese glioblastoma patients has not been elucidated systematically. In the present study, tumor tissues from 172 GBM patients were analyzed for MGMT protein expression by immunohistochemistry. Of these, 79 were also subjected to pyrosequencing for MGMT promoter methylation analysis. MGMT protein overexpression was found in 109/172 (63.4%) GBM samples. And no significant survival difference was observed between the patients with MGMT overexpression and low expression in terms of progression-free survival or overall survival ( P = 0.605 and P = 0.565, respectively). Meanwhile, MGMT promoter methylation was detected in 26/79 cases (32.9%), whereas 53/79 (67.1%) samples were unmethylated. Further survival analysis also revealed that MGMT promoter methylation status cannot predict patients progression-free survival and overall survival ( P = 0.906 and P = 0.548, respectively). The integrated analysis showed that there was significant negative correlation between MGMT protein expression and promoter methylation ( P = 0.004). These results underscore that, in Chinese GBM patients, (a) MGMT protein expression level was not a prognostic factor, (b) overall survival but not progression-free survival showed a trend toward increase in patients with MGMT promoter methylation, although the difference was not significant statistically and this observation has to be validated in larger patients cohort, (c) there was a significant correlation between MGMT protein expression in immunohistochemistry and MGMT promoter methylation by pyrosequencing. [ABSTRACT FROM AUTHOR]

Intense femtosecond (10−15 s) light pulses can be used to transform electronic, magnetic and structural order in condensed-matter systems on timescales of electronic and atomic motion. This technique is particularly useful in the study and in the control of materials whose physical properties are governed by the interactions between multiple degrees of freedom. Time- and angle-resolved photoemission spectroscopy is in this context a direct and comprehensive, energy- and momentum-selective probe of the ultrafast processes that couple to the electronic degrees of freedom. Previously, the capability of such studies to access electron momentum space away from zero momentum was, however, restricted owing to limitations of the available probing photon energy. Here, using femtosecond extreme-ultraviolet pulses delivered by a high-harmonic-generation source, we use time- and angle-resolved photoemission spectroscopy to measure the photoinduced vaporization of a charge-ordered state in the potential excitonic insulator 1T-TiSe2 (refs 12, 13). By way of stroboscopic imaging of electronic band dispersions at large momentum, in the vicinity of the edge of the first Brillouin zone, we reveal that the collapse of atomic-scale periodic long-range order happens on a timescale as short as 20 femtoseconds. The surprisingly fast response of the system is assigned to screening by the transient generation of free charge carriers. Similar screening scenarios are likely to be relevant in other photoinduced solid-state transitions and may generally determine the response times. Moreover, as electron states with large momenta govern fundamental electronic properties in condensed matter systems, we anticipate that the experimental advance represented by the present study will be useful to study the ultrafast dynamics and microscopic mechanisms of electronic phenomena in a wide range of materials. [ABSTRACT FROM AUTHOR]

By using laser molecular beam epitaxy (L-MBE), atomic scale epitaxid growth of BaTiO3(BTO) thin films on SrTiO3 (STO) substrates is achieved. Measurements of reflection high energy electron diffraction (RHEED), X-ray diffraction (XRD), scanning electron microscopy, and transmission electron microscopy reveal that the BTO films are c-axis oriented single crystals with smooth surface. The multi-layer ferroelectric/superconducting heterostructures are also prepared and the ferroelectric properties of BTO films are studied. The results show that by using L-MBE technique, high quality BTO films and improved device performance can be obtained. [ABSTRACT FROM AUTHOR]

Glioma, the most common form of primary malignant brain tumors, is graded based solely on histopathological appearance, which has led to prognostic discrepancies. This study aimed to establish a new glioma grading model by analyzing the expression of Bone Morphogenetic Protein 2 (BMP2) mRNA in patients with gliomas as well, named the Histopathological-BMP2 (HB) system. Clinical information was collected from 692 patients from the Chinese Glioma Genome Atlas database. According to pathological glioma subtypes and the expression of BMP2 mRNA in tumor tissues, the new subtypes HBs, HBh, HBm and HB1 were established, with BMP2 expression highest in HBs and lowest in HB1. Survival periods were analyzed. Based on this, the expression of three BMP2 receptors (BMPR1A, BMPR1B, and BMPR2) was also analyzed, which was related to the prognosis of patients. This new classification model was validated in further groups of patients from the CGGA database (n = 291) and the Cancer Genome Atlas (n = 625). A new glioma grade (HB grade) based on histopathology and BMP2 expression can predict the prognosis of glioma patients, with BMPR1B and BMPR2 expression indicating a different prognosis in different types of gliomas. The higher the concentration of BMP2, the better the prognosis of patients. [ABSTRACT FROM AUTHOR]

As the advanced functional materials, silver nanoparticles are potentially useful in various fields such as photoelectric, bio-sensing, catalysis, antibacterial and other fields, which are mainly based on their various properties. However, the properties of silver nanoparticles are usually determined by their size, shape, and surrounding medium, which can be modulated by various synthesis methods. In this review, the fabrication methods for synthesizing silver nanoparticles of different shapes and specific size are illustrated in detail. Besides, the corresponding properties and applications of silver nanoparticles are also discussed in this paper. [ABSTRACT FROM AUTHOR]