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FOXA1, as a pioneering transcription factor, has been shown to drive prostate cancer progression. Previous studies showed that FOXA1 expression in prostate cancer was positively associated with cancer angiolymphatic invasion and metastasis. However, the mechanism underlying the correlation between FOXA1 and prostate cancer angiolymphatic invasion and metastasis remains largely unclear. Herein, we set out to investigate the role of FOXA1 in the interactions between prostate cancer cells and endothelial cells. Endothelial cells' phenotypes were assessed through CCK‐8 assay, Transwell migration assay, and tube formation assay. The angiogenic factors acting on endothelial cells mediated by FOXA1were characterized by RNA-seq, qPCR array, angiogenesis cytokines array, and ELISA assay. The impact of FOXA1 on tumor angiogenesis was examined in a xenograft model in nude mice. The effect of FOXA1 on prostate cancer angiogenesis was validated on a primary prostate cancer tissue microarray. FOXA1 expression in prostate cancer cells promoted endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, FOXA1 increased pro-angiogenic factors production, including EGF, Endothelin-1, and Endoglin. Moreover, in vivo study showed that FOXA1 facilitated tumor angiogenesis. Furthermore, clinical samples investigation indicated that FOXA1 enhanced prostate cancer angiogenesis. Overall, these findings illustrated a tumor angiogenesis-promoting role of FOXA1 in prostate cancer.

Real‐time power dispatch can coordinate wind farms, automatic generation control units and non‐automatic generation control units. In real‐time power dispatch, the probable wind power forecast errors should be appropriately formulated to ensure system security with high probability and minimize operational cost. Previous studies and the authors' onsite tests show that Cauchy distribution effectively fits the “leptokurtic” feature of small‐timescale wind power forecast errors distributions. In this paper, a chance‐constrained real‐time dispatch model with the wind power forecast errors represented by multivariate Cauchy distribution is proposed. Since the Cauchy distribution is stable and has promising mathematical characteristics, the proposed chance‐constrained real‐time dispatch model can be analytically transformed to a convex optimization problem considering the dependence among wind farms’ outputs. Moreover, the proposed model incorporates an affine control strategy compatible with automatic generation control systems. This strategy makes the chance‐constrained real‐time dispatch adaptively take into account both the potential power ramping requirement and power variation on transmission lines caused by the generation adjustment to offset the wind power forecast errors in real‐time power dispatch stage. Numerical test results show that the proposed method is reliable and effective. Meanwhile it is very efficient and suitable for real‐time application.

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml-1, 10.1-20.0 ng ml-1, and >20.0 ng ml-1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml-2, 0.297 ng ml-2, and 1.180 ng ml-2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The α7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with α7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility. To overcome the challenges with orthosteric agonists, we have identified a novel selective α7 positive allosteric modulator (PAM), BNC375. This compound is selective over related receptors and potentiates acetylcholine-evoked α7 currents with only marginal effect on the receptor desensitization kinetics. In addition, BNC375 enhances long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo. Systemic administration of BNC375 reverses scopolamine-induced cognitive deficits in rat novel object recognition and rhesus monkey object retrieval detour (ORD) task over a wide range of exposures, showing no evidence of an inverted U-shaped dose-effect curve. The compound also improves performance in the ORD task in aged African green monkeys. Moreover, ex vivo 13C-NMR analysis indicates that BNC375 treatment can enhance neurotransmitter release in rat medial prefrontal cortex. These findings suggest that α7 nAChR PAMs have multiple advantages over orthosteric α7 nAChR agonists for the treatment of cognitive dysfunction associated with CNS diseases. SIGNIFICANCE STATEMENT: BNC375 is a novel and selective α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) that potentiates acetylcholine-evoked α7 currents in in vitro assays with little to no effect on the desensitization kinetics. In vivo, BNC375 demonstrated robust procognitive effects in multiple preclinical models across a wide exposure range. These results suggest that α7 nAChR PAMs have therapeutic potential in central nervous system diseases with cognitive impairments.

This paper presents a two-stage optimization method for a coupled capacity planning and operation problem, cast within the economical operation of Regional Integrated Energy System. The first stage optimization of the proposed model represents a regional integrated energy system planner whose purpose is to minimize its energy and environmental cost, while the second stage is an operation problem whose primary role is to achieve the optimal operation scheme of the system. The regional integrated energy system planner pursues best interests by co-optimizing the capacity configuration and power output of individual energy supply module, while the regional integrated energy system maximizes the installed capacity of renewable energy sources and minimizes the environmental costs. To illustrate the advantage of the proposed method, the NSGA-II algorithm and the mixed integer linear programming method are implemented to solve the model based on simulation. Besides, application of the optimization method proposed to the energy infrastructure of a regional integrated energy system in China is discussed, and the results obtained through simulation are compared to the bi-level optimization objectives. The results show that the proposed method is economical and effective in practical application.

Background: Until recently, most enucleation techniques of the prostate were performed with the application of morcellator. We introduce a modified enucleation technique of thulium laser with non-morcellator approach, which is about incising and vaporizing remaining prostate tissue instead of a morcellator.Methods: A retrospective evaluation of 223 patients undergoing ThuLEP from January 2014 to December 2015 was performed in our institution. One hundred five of the patients used morcellator while the other 118 used non-morcellator approach. All patients were assessed with the International Prostate Symptom Score (IPSS), quality of life (Qol), ultrasonography, serum prostate-specific antigen (PSA), maximal urine flow rate (Qmax), and postvoid residual urine volume (PVR). We reassessed these parameters at 1-, 3-, 6-, and 12-months after operation. Operative time, perioperative, and postoperative complications were also recorded.Results: Significant improvement was noted in the IPSS, QoL, Qmax, and PVR in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. Comparisons of the total operation time and enucleation time demonstrated no significant differences between the two groups. Our non-morcellator approach needed more time to incise and vaporize the enucleated tissue compared to morcellation when the prostate volume was about 40–80 ml (p < 0.05), while it showed a significant lower rate of superficial bladder injury than using morcellator (p < 0.05). There were no significant differences in other complications between the two groups (p > 0.05).Conclusions: Our modified technique is a safe and effective procedure for the treatment of BPH avoiding the potential complications caused by morcellator.

Background Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT. Methods PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot. Results Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.

Integrating electric heater (EH) and heat storage (HS) into power systems is a feasible solution to reduce wind power curtailment. However, most researches consider the capacities optimization without their distribution. Based on a practical power grid with eight buses, utilizing the DC power flow model together with the capacity and operation constraints of EH, HS and other power units gives the mathematic model of the integrated energy system. On this basis, applying the economic benefit as the optimization objective gives the optimal capacities and distribution of EH and HS to satisfy certain proportion of heat load. Besides, the concept of “generalized energy storage” is put forward to provide an explanation of the regulating ability of power generation and consumption of a region. The results show that the economic benefit in the optimal case with the optimal distribution of EH and HS is 44.65% higher compared to the case that maintains the same power transmitted after installing EH and HS, and 1.76% higher than that in the case that allocates the electric heaters equally. Besides, the influence of the coal price is nearly twice of the HS price, and 4 times of the EH price on economic benefit.

To compare the safety and efficacy of thulium laser enucleation of the prostate (ThuLEP) versus thulium laser resection of the prostate (TmLRP) in small prostates (≤ 30 g) and to test the validity of ThuLEP for bladder neck contracture (BNC). A total of 115 patients with benign prostatic hyperplasia (BPH) (prostate size ≤ 30 g) were randomly assigned to ThuLEP (n = 56) or TmLRP (n = 59). All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery. Baseline characteristics of the patients, perioperative data, postoperative outcomes and complications were assessed. Comparisons of the baseline and perioperative data demonstrated no significant differences between the ThuLEP and TmLRP groups. Significant improvement was noted in the International Prostate Symptom Score, quality of life, maximal urinary flow rate (Qmax) and post-void residual volume (PVR) in both groups at the 12-month follow-up, and assessment showed no differences in these parameters between the two groups. The TmLRP group showed a significantly higher rate (13.6%) of BNC than the ThuLEP group (1.8%; P = 0.045). There were no significant differences in other complications between the two groups (P > 0.05). ThuLEP and TmLRP are both safe and efficient procedures for the treatment of patients with small prostate volume, while ThuLEP can significantly reduce the risk of BNC in patients with a small prostate because the procedure enucleates adenomas without thermal damage to the bladder neck.

Background Prostate cancer is one of the most common malignancies. Increasing evidence suggested that endothelial cells may contribute to prostate cancer progression and metastasis. Most recently, autophagy has been proposed to plays a significant role in tumorigenesis and metastasis. Also, it is reported that downregulation of androgen receptor (AR) induces autophagy in prostate cancer cells. However, the underlying mechanisms remain unclear. Here, we aim to explore the role and mechanisms of endothelial cell in prostate cancer progression. Methods The coculture system was established to test the effect of endothelial cells on prostate cancer cells. We performed antibody array and ELISA were used to profile the cytokine expression pattern of endothelial cells in supernatant. Western blot and RT-PCR were used to determine the mechanism by endothelial cells to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic xenograft mouse models and drug treatment study were conducted to determine the role of endothelial cells in promoting metastatic potential in vivo. Results We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo. Conclusions Together, our data establish the function for endothelial cells in tumor metastasis and propose new drug target for mCRPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0884-2) contains supplementary material, which is available to authorized users.

Due to the nature of fluctuation and intermittence, integration of renewable energy sources (RESs) requests more flexibility of power systems. However, the “heat-led” operation mode limits the adjustability of combined heat and power (CHP) plants, and reduce the accommodation of RESs. This paper studies an integrated thermal and power system and introduces a phase-change heat storage (HS) facility into the CHP plant to improve the adjustability, where the heat released from the extraction steam is not consistent to the heat load at each moment. Furthermore, the heat transfer processes in the HS facility are modelled as a thermal resistance network, which provides the feasibility for analyzing the integrated system in a unified model. On this basis, the operation plan of the integrated system is optimized by the linear programming (LP) method to minimize the wind energy loss. The results show that: 1) HS facility installation increases the flexibility of power system, and reduces the wind energy loss from 18.7% to 11.2%. 2) Heat transfer processes should be carefully taken into account for precisely setting the power generations of each plant. 3) The phase-change temperatures of HS materials should be between 90 °C and 100 °C for the maximum wind power accommodation.

The α7 nicotinic acetylcholine receptor (nAChR) is a promising target for the treatment of cognitive deficits associated with psychiatric and neurological disorders, including schizophrenia and Alzheimer's disease (AD). Several α7 nAChR agonists and positive allosteric modulators (PAMs) have demonstrated procognitive effects in preclinical models and early clinical trials. However, despite intense research efforts in the pharmaceutical industry and academia, none of the α7 nAChR ligands has been approved for clinical use. This chapter will focus on the α7 nAChR ligands that have advanced to clinical studies and explore the reasons why these agents have not met with unequivocal clinical success.

Simultaneous measurement of curvature and temperature by monitoring the transmission spectrum of a hybrid-structure fiber sensor which consists of two peanut-shape structures and a FBG is proposed in this paper. Besides the transmission spectrum, reflection spectrum of this hybrid-structure sensor can also be used for the curvature measurement. Unlike the wavelength demodulation of the transmission spectrum, the reflection spectrum which employs the intensity demodulation has an evident advantage that we can realize the measurement of curvature by using a relatively simple optical power meter instead of an elaborate and expensive OSA in practical application, which can reduce the cost well.

RGB lasers have been widely used as light sources in projectors, endoscopes, HUD(Head up Displays) and many other displays. In this study, we designed a current driver circuit for an ultra-compact RGB laser, which allows for high speed driving current modulations. This characteristic is suitable for scanning display in many occasions. The laser current driver circuit is consisted of the current driver and the temperature controller. The current driver has three independently high-speed current modulation channels. We have tested the P-I performance of the RGB laser and the highest current modulation speed is 1.55MHz.

When the traditional Genetic Algorithm(GA) is used for unmanned aerial vehicle(UAV) path planning, the shortcomings of local search ability are reflected when the planning time is more urgent. To address this shortcoming, this paper proposes an improved genetic algorithm that limits the new gene's generating region. The generating region of the evolution operator is dynamically adjusted. The algorithm is applied to UAV online path planning for tracking moving target. The simulation results show that the method enhances the local search ability of the algorithm and improves the searching efficiency. UAV online path planning can be completed well with the improved genetic algorithm.

Background : While localized prostate cancer (PCa) can be mitigated by surgery and radiation, metastatic PCa remains a challenge to treat. Androgen deprivation therapies and androgen receptor (AR) pathway inhibitors are mainstay treatments for advanced PCa. Yet, resistance often develops leading to castration-resistant prostate cancer (CRPC). Forkhead Box A1 (FOXA1) is a pioneer transcription factor that plays pivotal roles in regulating AR activity and promoting epithelial differentiation. Studies have shown that FOXA1 is frequently downregulated in CRPC tumors. Congruently, FOXA1 loss is reported to induce aberrant AR signaling, epithelial-mesenchymal transition, and PCa de-differentiation. However, the role of FOXA1 in regulating PCa immune response, an area of much interest recently, has not been reported. CRPC has shown poor response to immune checkpoint inhibitors, due to its immunosuppressive nature. A better understanding of the tumor intrinsic mechanisms regulating PCa tumor immunity will inform the design of better targeted immunotherapeutic approaches. Methods: We performed RNA-seq, ChIP-seq, qPCR, western blot, and ELISA analyses to evaluate how FOXA1 regulates inflammatory response genes. We utilized an in vitro macrophage infiltration transwell assay, in which M2-like macrophages were added to the upper chamber and PCa cells were plated in the lower chamber, to examine how perturbations to PCa cells affect macrophage migration. Finally, we performed bioinformatic analyses of patient datasets to confirm the clinical relevance of FOXA1 repression of inflammatory genes in PCa. Results: Through integration of RNA-seq and ChIP-seq data, we uncovered a novel function of FOXA1 in suppressing inflammatory response pathways. In accordance, patient data analyses revealed that inflammatory response genes were upregulated in FOXA1-low PCa tumors. Mechanistically, we showed that FOXA1 proteins bound an intragenic enhancer of Hypoxia-inducible factor 1-alpha (HIF1A) gene to directly repress its expression, such that FOXA1 loss induced HIF1A upregulation. We further showed that Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) became upregulated upon FOXA1 depletion in a HIF1A-dependent manner. This led to infiltration by immunosuppressive, tumor promoting M2-like macrophages. Inhibiting this HIF1A-CCL2 axis with a HIF1A inhibitor or CCL2 neutralizing antibody blocked macrophage infiltration. Future studies using immunocompetent mouse models are needed to confirm the effect of FOXA1 on macrophage infiltration in vivo and evaluate the preclinical potential of targeting the FOXA1-HIF1A-CCL2 axis in CRPC. Conclusion: This study proposes a novel role for FOXA1 loss in promoting macrophage infiltration via the HIF1A-CCL2 axis. Moreover, our findings suggest that targeting this axis may be a promising approach for the treatment of FOXA1-low CRPC tumors.

Integrated energy system (IES) models are considered effective tools to improve energy efficiency and reduce energy supply cost by integrating multiple energy carriers. Building complexes have electricity, heat and cold demands, and the use of IES can help meet these demands effectively. The type, capacity and operation strategy of battery energy storage systems (BESS) have a crucial influence on the planning results of IES. In this paper, the two operation strategies of BESS suitable for different scenarios are firstly introduced. Based on the two strategies of BESS, firstly the optimal planning model with the annual total cost of IES as the optimal objective has been established in detail. Secondly, the technical characteristics and economic parameters of different batteries are considered in the optimal planning of BESS. A hybrid energy system in a residential complex is taken as a case study to demonstrate the application of the proposed method. The simulation results show that the operation strategy is successfully conducted and the proposed method is economical and effective. In addition, the different strategies of BESS proposed could also provide support for the operation strategy of IES under the energy development.

With the proliferation of smartphones and tablets, large amounts of data are generated at the edge of the network. Edge computing becomes a promising paradigm for the processing of large amounts of data due to its characteristics of low latency, high data throughput, and low traffic pressure. However, the increasing requirements of the novel terminal applications and services on timely content delivery. Further reducing the latency and improving the data service quality are still the challenges for the data processing. Caching strategy is an effective solution to address these issues. In order to better save the cache space of edge nodes to cache more high heat files, thereby to improve the quality of user data services, a cache replacement strategy based on priority and LRU is proposed. In this strategy, the files to be replaced are selected according to the LRU principle in each priority queue. Then the re-access weight of these files is calculated. The file with the smallest re-access weight is selected to finally be replaced. To further improve the quality of data services and reduce user access latency, a cache prefetching strategy based on Bayesian network theory is presented. This strategy selects the files to be prefetched based on the Bayesian network, and then selects edge nodes with lower loads to place these files. The proposed strategies are evaluated in an edge computing environment built over a campus network. Extensive experimental results show that the proposed cache replacement strategy outperforms the benchmarks in terms of cache hit rate, delay saving rate and cost saving rate. The proposed cache prefetching strategy performs better than the benchmarks in terms of prefetching hit rate and memory load consuming.

Gear transmission is a major form of power transmission, of which the reliability greatly affects the life of many mechanical devices. Gears have two main failure modes, namely tooth surface pitting and tooth root fracture. Tooth surface pitting is mainly due to excessive contact stress and tooth root fracture is mainly due to excessive bending stress. In this paper, we focus on increasing the tooth root strength of spur gears by optimizing the hob tip contour. A hobbing simulation model is developed to generate the tooth root profile from its corresponding hob tip contour. The hob tip contour is defined by introducing a Bezier curve of five points. An optimization process based on genetic algorithm and FEM analysis is designed to find the optimal tooth root profile with larger bending load capacity. The optimal tooth root profile and its corresponding hob tip contour can be obtained for engineering application. This work provides a theoretical basis for spur gear design with a high bending load capacity.

This paper investigated the dimensional variation problem of high defect rate of front wheel camber for Macpherson suspension, found the factors affecting dimensional deviation, determined the contribution of each factor for the camber by contrasting the 3D tolerance simulation analysis results based on 3DCS with the physical assembly verification results, and then solved the Macpherson suspension camber problem of high defect rate at last by optimizing those components tolerances with greater contributive factors and monitoring dimensional variation of these key factors in production at the same time.

Virtual reality technology can construct the approximate nautical environment required for navigational fix training, which can not only make positioning teaching more intuitive and vivid, but also make trainees physically and psychologically immersed into training, thereby greatly improving the training quality. In this paper, a digital watermarking-based Image construction method for Navigational Fix training is proposed, with which the observational information will be embedded previously: the invisible watermark carrying the coordinate information is embedded in the video frame, and the observation value will be obtained after extracting the coordinate information in the observation picture. Using this method, the observation error caused by the projection distortion is bypassed, so that the accuracy of training feedback of multiple observation devices can be guaranteed. Thereby the overall system's accuracy requirements and construction difficulty is reduced.

The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression.

Although tau pathology, behavioral deficits, and neuronal loss are observed in patients with tauopathies, the relationship between these endpoints has not been clearly established. Here we found that rTg4510 mice, which overexpress human mutant tau in the forebrain, develop progressive age-dependent increases in locomotor activity (LMA), which correlates with neurofibrillary tangle (NFT) pathology, hyperphosphorylated tau levels, and brain atrophy. To further clarify the relationship between these endpoints, we treated the rTg4510 mice with either doxycycline to reduce mutant tau expression or an O-GlcNAcase inhibitor Thiamet G, which has been shown to ameliorate tau pathology in animal models. We found that both doxycycline and Thiamet G treatments starting at 2 months of age prevented the progression of hyperactivity, slowed brain atrophy, and reduced brain hyperphosphorylated tau. In contrast, initiating doxycycline treatment at 4 months reduced neither brain hyperphosphorylated tau nor hyperactivity, further confirming the relationship between these measures. Collectively, our results demonstrate a unique behavioral phenotype in the rTg4510 mouse model of tauopathy that strongly correlates with disease progression, and that early interventions which reduce tau pathology ameliorate the progression of the locomotor dysfunction. These findings suggest that better understanding the relationship between locomotor deficits and tau pathology in the rTg4510 model may improve our understanding of the mechanisms underlying behavioral disturbances in patients with tauopathies.

Provision of social service is one of the most significant roles of the police. A review of the related literature in policing seems to reveal that empowerment holds significance for frontline officers who are largely responsible for social service delivery. This study examines the possible relationships between police social service role strain (PSSRS) and police social service psychological empowerment (PSSPE) among frontline police officers in China. This study adopts a two-phase (quantitative and qualitative approaches) sequential explanatory design. In the first phase, a questionnaire is used to collect data from a sample of 200 frontline community patrol officers in Shenzhen Public Security Bureau, China. After conducting the quantitative analysis, the author uses in-depth interviews to explore the nature of PSSRS and PSSPE from 12 selected interviewees’ insights. According to the results of the survey and in-depth interviews, the participants report a comparatively high level of PSSRS and a low level of PSSPE. It has been found that there are significantly negative correlations between PSSRS and PSSPE in the Chinese police organization. The Chinese police force is suggested to provide effective interventions for individual experience of psychological empowerment by continuously committing to the organizational philosophy of community policing in response to the PSSRS among frontline police officers.

In northern China, wind curtailment and environmental pollution from the widespread use of traditional heating methods cause huge economic losses. This paper proposes an emerging heating te...

Salmonella Enteritidis (SE) is a highly adapted pathogen causing severe economic losses in the poultry industry worldwide. Chickens infected by SE are a major source of human food poisoning. Vaccination is an effective approach to control SE infections. This study evaluated the immunogenicity and protective efficacy of a SE sptP deletion mutant (C50336ΔsptP) as a live attenuated vaccine (LAV) candidate in chickens. 14 day-old specific pathogen-free (SPF) chickens were intramuscularly immunized with various doses of C50336ΔsptP. Several groups of chickens were challenged with the virulent wild-type SE strain Z-11 via the same route at 14 days post vaccination. Compared to the control group, the groups vaccinated with 1 × 106, 1 × 107 and 1 × 108 colony-forming units (CFU) of C50336ΔsptP exhibited no clinical symptoms after immunization. Only slight pathological changes occurred in the organs of the 1 × 109 CFU vaccinated group. C50336ΔsptP bacteria were cleared from the organs of immunized chickens within 14 days after vaccination. Lymphocyte proliferation and serum cytokine analyses indicated that significant cellular immune responses were induced after the vaccination of C50336ΔsptP. Compared to the control group, specific IgG antibody levels increased significantly in vaccinated chickens, and the levels increased markedly after the challenge. The 1 × 107, 1 × 108, and 1 × 109 CFU vaccinated chickens groups showed no clinical symptoms or pathological changes, and no death after the lethal challenge. Whereas severe clinical signs of disease and pathological changes were observed in the control group chickens after the challenge. These results suggest that a single dose of C50336ΔsptP could be an effective LAV candidate to against SE infection in chickens.

Aging is a major risk factor for prostate cancer (PCa), and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors (ARs) by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA (shRNA), matrix metalloproteinase (MMP) expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

Objective To compare intra-arterial chemotherapy combined with intravesical chemotherapy with intravesical chemotherapy alone in the treatment of high-risk non-muscle invasive bladder cancer (HRBC) after thulium laser resection of a bladder tumor (TmLRBT). From January 2009 to December 2013, 283 patients with HRBC were randomly assigned to the combined group (group A, n = 141) or intravesical chemotherapy–alone group (group B, n = 142) after TmLRBT. Intra-arterial chemotherapy was administered after initial TmLRBT, with 3 courses at 4-week intervals. Each course consisted of cisplatin (50 mg/m2) and epirubicin (30 mg/m2). Intravesical chemotherapy was administered in both groups, including an immediate 50 mg of epirubicin instillation after TmLRBT and weekly maintenance for 8 weeks, followed by monthly maintenance for 1 year. The recurrence rate was 29.1% (41/141) in group A and 42.9% (61/142) in group B, with a significant difference (p = 0.01). The progression rate was 15.6% (22/141) in group A and 25.3% (36/142) in group B, with a significant difference (p = 0.039). Patients with concomitant carcinoma in situ (CIS) also had a lower recurrence rate and progression rate in group A compared to those in group B (p = 0.006 and p = 0.03, respectively). On univariate and multivariate logistic regression analyses, patients with low-grade histology had a higher reccurrence-free rate. Multivariate COX analysis of tumor-related factors suggested that concomitant CIS was the only significant prognostic factor associated with poorer recurrence-free survival and progression-free survival. Intra-arterial chemotherapy combined with intravesical chemotherapy could reduce the risk of recurrence and progression compared to intravesical chemotherapy alone in HRBC.

This paper presents a hybrid method by combining cultural algorithm (CA) and particle swarm optimization (PSO) to solve the economic load dispatch (ELD) problem with valve-points effect. The proposed method is called SCAPSO. In SCAPSO, a new velocity update strategy is employed to replace the standard one in PSO, which can enlarge the search space and speed up the convergence. SCAPSO not only has the advantages of PSO, but also utilizes the CA to increase the diversity of the population so as to improve the global search ability. To verify the performance of the proposed method, the power system with 40 generating units is tested. Simulation results show the efficiency, convergence characteristic and robustness of proposed SCAPSO.

Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders1,2,3. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested4,5,6. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown1. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor–null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor7. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.

Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland possesses a stronger inclination for PCa than transition zone. We previously found a variety of genes that differently expressed among different prostate stromal cells, including LIM domain only 2 (LMO2) which highly expressed in peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts (CAFs) compared to transition zone derived stromal cells (TZSCs). Studies on its role in tumors have highlighted LMO2 as an oncogene. Herein, we aim to study the potential mechanisms of stromal LMO2 in promoting PCa progression. The in vitro cells co-culture and in vivo cells recombination revealed that LMO2 over-expressed prostate stromal cells could promote the proliferation and invasiveness of either prostate epithelial or cancer cells. Further protein array screening confirmed that stromal LMO2 stimulated the secretion of Interleukin-11 (IL-11), which could promote proliferation and invasiveness of PCa cells via IL-11 receptor α (IL11Rα) - STAT3 signaling. Moreover, stromal LMO2 over-expression could suppress miR-204-5p which was proven to be a negative regulator of IL-11 expression. Taken together, results of our study demonstrate that prostate stromal LMO2 is capable of stimulating IL-11 secretion and by which activates IL11Rα - STAT3 signaling in PCa cells and then facilitates PCa progression. These results may make stromal LMO2 responsible for zonal characteristic of PCa and as a target for PCa microenvironment-targeted therapy.

In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely.

To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group (n = 45) and 2D-LPN group (n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC (P

Secondary injury exacerbates the extent of spinal cord insults, yet the mechanistic basis of this phenomenon has largely been unexplored. Here we report that broad regions of the peritraumatic zone are characterized by a sustained process of pathologic, high ATP release. Spinal cord neurons expressed P2X7 purine receptors (P2X7R), and exposure to ATP led to high-frequency spiking, irreversible increases in cytosolic calcium and cell death. To assess the potential effect of P2X7R blockade in ameliorating acute spinal cord injury (SCI), we delivered P2X7R antagonists OxATP or PPADS to rats after acute impact injury. We found that both OxATP and PPADS significantly improved functional recovery and diminished cell death in the peritraumatic zone. These observations demonstrate that SCI is associated with prolonged purinergic receptor activation, which results in excitotoxicity-based neuronal degeneration. P2X7R antagonists inhibit this process, reducing both the histological extent and functional sequelae of acute SCI.

Different fault characteristics are shown in the micro grid due to distributed generators (DGs) interfaced with inverters. Overcurrent protection cannot operate correctly in this type of micro-grid. In this paper, we analyze the characteristics of the fault currents which are supplied by photovoltaic (PV) units, permanent magnet synchronous wind generators (PMSG) and power storages. These generators are always seen as typical inverter-interfaced DGs. Besides, the performance of overcurrent protection schemes is studied by taking a typical isolated micro-grid as the example. Due to the limited fault current supplied by DGs and frequency deviation of fault current waveform, the overcurrent relays can not operate correctly. Voltage controlled overcurrent relays work well if the fault is not very serious. Due to its reliability in fault detection, the differential protection is suggested to be used in the micro-grid with inverter-interfaced DGs. Finally, a practical protection configuration scheme is proposed for the micro grid in this paper. Differential relays are suggested to act as primary protection and voltage controlled overcurrent relays act as backup protection in the proposed scheme. Digital simulations are performed to verify the fault analysis results and proposed protection configuration schemes. The proposed protection configuration schemes have been used in an isolated micro grid and work well.

The first stage of Wuhan Metro line 6 was designed to utilize shield method for tunnel construction, which consists of two sections, one from sport center south station to CheCheng East Road station, and the other from CheCheng East Road station to JiangCheng street station. Selection of shield machine involves geological condition, hydrologic geology, and unfavorable geology of the route on the basis of preliminary investigation. What’s more the pumping test also will help shield machine selection for some special geology. With the aim to provide technical support for construction design, this paper is focus on the shield machine selection by analyzing data of geological exploration and comparing different shield methods.

Focusing on the exceptional jobs that need to visit machines in multiple job shop cells in Cellular Manufacturing System (CMS), the inter-cell moves between batch machines and discrete machines is considered and a combinational ant colony optimization (CACO) approach is proposed to solve the problem of scheduling in multiple job shop cells. The CACO uses different heuristic information in assignment, sequencing and batching processes respectively, and updates the pheromone trail when the whole solution is constructed, so that cooperative scheduling is achieved. The experimental results show the CACO has significant advantages comparing with CPLEX with respect to makespan and utilization rate of batch processing machine.

This paper introduces the operation and control strategies of wind power in Dispatching Center of China's largest provincial grid of wind power in capacity and proportion, West Inner Mongolia Power Grid. Firstly, off-line calculation of static voltage stability, transient stability, small signal stability, thermal stability and short circuit current of the power system with a large scale wind power has been done to make sure the grid is safe in both steady state and dynamic process. Secondly, the system of wind power foresting has been built and the forecasting result of a single wind farm, wind zones and the whole system can be achieved. Based on wind power forecasting, daily power balance with wind power has been done to accommodate wind power as much as possible, especially in valley time. Thirdly, the aim of automatic generation control and automatic voltage control has been achieved in some of the wind farms and the project is still under researching and developing to make most of the wind farms under closed-loop control in the near future.

To investigate the pharmacokinetics of single dose morphine inhaled by modified ultrasonic nebulizer versus intravenous administered in ventilated dogs.Six healthy dogs were randomly assigned to receive nebulized or intravenous morphine and crossed over to the alternative medication 1 week after. Morphine was nebulized by modified ultrasonic nebulizer (YuYue 402A, Jiangsu, China). Arterial blood was sampled every minute during the 10 min of administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, 240, and 360 min after the administration for the determination of morphine concentration by RP-HPLC.The main pharmacokinetic parameters of morphine by inhaled and intravenous administration were: MRT 59±14 min versus 19±4 min, T(1/2) 21.9±5.1 min versus 3.3±1.0 min, T(max) 23.0±2.7 min versus 8.8±2.4 min, C(max) 0.245±0.09 mg·L⁻¹ versus 1.09±0.32 mg·L⁻¹, AUC(0-∞) 9.7±1.1 mg·min·L⁻¹ versus 15.2±7.2 mg·min·L⁻¹, CL 0.069±0.019 L·min⁻¹·kg⁻¹ versus 0.063±0.028 L·min⁻¹·kg⁻¹, and the absolute bioavailability of inhaled morphine was 35.5±10%. There were no significant differences (p0.05) between inhaled and intravenous morphine in AUC and CL. As expected, the T(½) and MRT of inhaled morphine were significantly greater than those of intravenous morphine.Morphine nebulized by ultrasonic nebulizer can be rapidly and extensively absorbed by lungs in ventilated dogs.

EU's eLearning initiatives attempt to mobilize all actors in its member states in order to accelerate changes in the education and training systems for Europe's move to a knowledge-based society. This paper examines EU's eLearning action plans with their aims and tools since 1990s, esp. the latest ‘European Digital Agenda’ for fulfilling the overall objectives set in ‘Europe 2020 Strategy’ for smart growth, sustainable growth and inclusive growth. It sheds light on China's construction of a digital society in future.

ID management method is the foundation to implement and maintain DHT overlays, especially for Constant Degree DHTs based on de Bruijn and Kautz, because their topologies are not incrementally expandable and using bit-shifting route schema etc. However, corresponding researches on Constant Degree DHTs are scarce, and realized Constant Degree DHTs usually use pure centralized or distributed ID management methods simply, thus cannot guarantee overlay's balance with low cost both in theory and practice. Analyzing the universal tree structures of Constant Degree diagraph, we propose an ID management method based on the internal structure Routing Forest, which regularly aggregates local balancing information to guide new nodes' joining for overall balance. The experimental results validate, with low maintenance and routing message overhead, node IDs' length differ by at most 2 in system, thus the load balancing is efficiently ensured.

Using advanced computer information technology and power system, Real-time Environment Protecting Supervision and Control System (REPSCS) of heavy loads in the Inner Mongolia Electric Power Grid is studied. REPSCS can monitor the operation of the heavy load companies' main equipment and environmental protection electrical equipment. The operation data of those key equipment are collected, processed, transferred and applied, and the above features are integrated into an on-line monitoring and information management system to complete. At the same time, through the latch linkage between the main equipment and the key environmental protection equipment, we achieve the enterprise's environmental monitoring and control. The system is aimed at the practical needs of China's provinces and cities area design, system technology maturity and reliability of industrial applications have been tested in a very wide range of applications. As China's environment protection and energy facilities, environmental monitoring and penalties continue to increase; real-time monitoring system for the environmental protection facilities of the high load companies will be the first choice. Its market demand is very apparent and urgent. Therefore, this project is environmentally friendly energy saving, and it can promote scientific and technological progress and improve the operation and management level.

Constant degree P2P systems are turning into the P2P domain's promising hotspot due to their good properties. However, it is often hard to convert a standard constant degree digraph to a flexible DHT schema adapting to dynamic P2P environments. Thus, most research about constant degree P2P focus on DHT's construction and maintenance, while leaving optimization and supporting to upper-layer application behind, such as complex query, load balance, etc. Combining constant degree topology's bit-shift routing schema, we presents an efficient load balancing algorithm based on Reverse Spanning Tree (REST) for constant degree P2P systems. Using the statistic information in joining process, REST judges how many Virtual Servers that a new join super peer can run, and then join all virtual servers evenly and fast with low cost based on the Spanning Tree Peer Set. Experimental results show, without additional data structure, REST keeps the constant degree P2P system load-balanced by assuring each peer of owning a key space proportional to its capability.

A large amount of geological data can be obtained during tunnelling excavation. An on-going research project, AMADEUS (Adaptive Real-Time Geological Mapping Analysis of Underground Space), is being conducted to develop new methods to measure, process and implement this new geological datain real-time. This paper describes a statistical process developed to determine the shape and size of fractures, using the trace data that is observed along the tunnel wall. From field observations, fractures in sedimentary rocks are commonly rectangular and elongated parallel to their strikes. According to the possible geometric relationships between a fracture and a tunnel, four types of intersections (complete, longedge, short-edge and corner) are defined when fracture width is greater than tunnel diameter. The probabilities of occurrence of these different intersection types are related to tunnel diameter, size, and aspect ratio of fractures. The size and aspect ratio of fractures are then estimated directly from the observed number of occurrences of different types of intersection. Monte Carlo simulations using Excel and custom software are used to generate synthetic fracture populations and a cylindrical tunnel in a three-dimensional sedimentary rock mass. The results of these simulations, which validate the approach, are presented. Use of the estimators is demonstrated by an example. (A) This paper was presented at Safety in the underground space - Proceedings of the ITA-AITES 2006 World Tunnel Congress and the 32nd ITA General Assembly, Seoul, Korea, 22-27 April 2006. For the covering abstract see ITRD E129148. "Reprinted with permission from Elsevier".