Search

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

In order to improve the ability of cooperative spectrum sensing to withstand spectrum sensing data falsification (SSDF) attacks, a double reputation and multi-angle weight-based cooperative spectrum sensing (DRMW-CSS) method was proposed.Firstly, a scoring reputation was obtained by multiple iterations of historical local decision results, and an accuracy reputation was calculated on this basis.Secondly, secondary users (SU) were screened by double reputation and multiple reputation thresholds.Then, the impact of SSDF attacks on the screening method was judged and divided into three situations.Finally, the final global decision was made using the corresponding multi-angle weight data fusion decision method according to different situations.Simulation results show that the proposed method has good sensing accuracy when facing SSDF attacks with different attack strategies and probabilities, and has better anti-attack capability compared to traditional methods.

Overexpression of SNCA has been implicated in the pathogenesis of synucleinopathies, particularly Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). While PD and DLB share some clinical and pathological similarities, each disease presents distinct characteristics, including the primary affected brain region and neuronal type. We aimed to develop neuronal-type-specific SNCA-targeted epigenome therapies for synucleinopathies. The system is based on an all-in-one lentiviral vector comprised of CRISPR-dSaCas9 and guide RNA (gRNA) targeted at SNCA intron 1 fused with a synthetic repressor molecule of Krüppel-associated box (KRAB)/ methyl CpG binding protein 2 (MeCp2) transcription repression domain (TRD). To achieve neuronal-type specificity for dopaminergic and cholinergic neurons, the system was driven by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) promoters, respectively. Delivering the system into human induced pluripotent stem cell (hiPSC)-derived dopaminergic and cholinergic neurons from a patient with the SNCA triplication resulted in efficient and neuronal-type-specific downregulation of SNCA-mRNA and protein. Furthermore, the reduction in SNCA levels by the gRNA-dSaCas9-repressor system rescued disease-related cellular phenotypes including Ser129-phophorylated α-synuclein, neuronal viability, and mitochondrial dysfunction. We established a novel neuronal-type-specific SNCA-targeted epigenome therapy and provided in vitro proof of concept using human-based disease models. Our results support the therapeutic potential of our system for PD and DLB and provide the foundation for further preclinical studies in animal models toward investigational new drug (IND) enablement and clinical trials.

In order to support the implementation of “multidimensional orthogonal configured communication protection between communication modules as well as parameters and interference” in cognitive communication countermeasures scenarios, jamming effectiveness requires module level responsiveness.A penetrating jamming effectiveness evaluation method was proposed.Firstly, the core parameters of each signal processing module were selected as evaluation parameters.Secondly, analytic hierarchy process (AHP) and entropy weight method (EWM) were used to determine the weight of indicators.The coordination problem in AHP was solved through expert weight allocation, and the weight allocation problem in EWM was solved through non-uniform mapping.Finally, the subjective and objective weights were weighed through game theory, and the jamming effectiveness was judged by the technique for order preference by similarity to ideal solution (TOPSIS).By conducting evaluation experiments on the jamming performance of the Link16 data link, taking into account multiple aspects such as jamming types, number of jamming frequencies, jamming duration, and system types.Experiment results demonstrate that the penetration-based jamming performance evaluation method not only provides a more intuitive representation of the relationship between evaluation results and metric parameters, but also possesses excellent jamming discrimination capability.

Abstract Objective To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers. Methods This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers. Results A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P

The efficient extraction, storage, and visualization of geometric and semantic information is a key foundation for the operation of the building information modeling (BIM) platform. This study aims to develop a lightweight BIM system and optimize the system’s performance according to the specific characteristics of steel structures. This study proposes several novel techniques for extracting and decoupling the geometric and semantic information of components from industry foundation class (IFC) files. A redundancy removal approach combining the principal content analysis (PCA) algorithm and the Hausdorff-based comparison algorithm is proposed to identify standardized steel components, and a lightweight visualization method on Web3D for redundant instances is also presented. A loading mechanism of the level of detail (LOD) model based on a mesh simplification algorithm is presented to optimize the display efficiency. The developed system is evaluated by three steel structural models. Using the redundancy removal approach, the number of instances is decreased by 96.46% in less than 30 s and over 30 FPS (frame per second) is kept when rendering. Using the LOD loading mechanism, 95.38% of vertices and 98.46% of patches are eliminated under 50 mm precision. The experiment results indicate that users can quickly load large BIM models and fetch sufficient information from the website.

In this paper, semideterministic multi-input multi-output (MIMO) channel modeling is proposed for a tunnel with two types of cross sections. To be more consistent with the MIMO propagation characteristics of the measured data, ray tracing (RT) is used to simulate the specular components (SCs) and a directed path channel modeling method based on directive scattering model (DSM) is used to simulate the diffuse components (DCs), which has an important contribution in MIMO channel capacity. The performance of the proposed model is compared in terms of delay domain, angle domain, and channel capacity. By analyzing the DSM and the propagation graph based on the Lambertian scattering model (LSM), it was demonstrated that the proposed method is more suitable in terms of comprehensive performance.

Abstract Background Breast cancer is a serious threat to female health, and its incidence varies with education level (EL). In the present study, the association between EL and the risk of developing female breast cancer was investigated. Methods From May 2006 to December 2007, 20,400 observation subjects in Kailuan Cohort received questionnaires and were subjected to clinical examinations for data collection on baseline population characteristics, height, weight, lifestyle and past disease history. Then, these participants were followed up with from the date of recruitment to December 31, 2019. Cox proportional risk regression models were used to analyse the association between EL and the risk of developing female breast cancer. Results The cumulative follow-up period of 20,129 observation subjects that meet the inclusion criteria of this study was 254,386.72 person-years, and the median follow-up time was 12.96 years. During the follow-up period, 279 cases of breast cancer were diagnosed. In comparison with the low EL group, the risk of developing breast cancer was significantly higher in the medium (hazard ratio [HR] (95% confidence interval [CI]) = 2.23 (1.12–4.64)] and high [HRs (95% CI) = 2.52 (1.12–5.70)] EL group. Conclusion An increased risk of breast cancer was associated with a higher EL, and some certain factors, such as alcohol use and hormone therapy, may play a mediating role.

For the problem of communication jamming effectiveness, an effective jamming coefficient was proposed as an evaluation metric based on the correlation between jamming and communication signals, and the impact of orthogonal receivers was analyzed.Specially, minimum shift keying (MSK) and several typical binary modulation signals were chosen as the target communication and jamming signals, respectively.Jamming effectiveness evaluation was performed for the above mentioned scenario by deriving its theoretical bit error rate (BER) formulas.Moreover, for coherent jamming scenario with MSK being the jamming signal, the impact of its phase difference, frequency difference and delay on the jamming effectiveness were also systematically analyzed.The analysis suggests that to achieve better jamming effectiveness, different jamming modulation scheme should be chosen according to the signal-to-noise (SNR) of the jamming communication signal.Simulation has also shown that there is a good match between the derived theoretical analysis and numerical simulation of the proposed method effectiveness, which has proven its accuracy and validity.

Multi-GNSS PPP partial ambiguity resolution (PAR) can improve the fixing success rate and shorten the time to first fix (TTFF). Ambiguity subset selection based on the bootstrapping success rate sorting criterion (BSSC) is widely used in PPP PAR due to its ease of computation and comprehensive evaluation of the global quality of ambiguity solutions. However, due to the influence of unmodeled errors, such as atmospheric residuals and gross errors, ambiguity parameter estimation will inevitably introduce bias. For ambiguity parameters with bias, their variance will converge incorrectly and will not accurately reflect the estimation accuracy. As a result, the selected ambiguity subset based on the BSSC becomes inaccurate, affecting the fixing success rate and TTFF. Therefore, we proposed an improved multi-GNSS PPP PAR method based on a two-step sorting criterion (TSSC). This method aims to address the influence of inaccurate variance of ambiguity parameters, particularly those with low observation quality, on the ambiguity subset selection based on the BSSC. The ambiguity subset satisfying the preset success rate threshold is selected to reduce the influence of unconverged ambiguity on the TSSC. In the first step of the sorting process, the observations whose elevation angle is below 30° or whose posterior residual falls into the IGG3 model reduction domain are clustered together. The posterior observation weight criterion (POWC) instead of the BSSC is adopted to sort ambiguities to overcome the false convergence of variance of ambiguity parameters. In the second step of the sorting process, the remaining ambiguities with reasonable variances are sorted based on the BSSC. Finally, the bottom ambiguity is removed one by one from the ambiguity subset sorted based on the two-step sorting criterion (TSSC) until the requirements of the ratio test for LAMBDA are met. The static data from 10 MGEX stations over a period of 30 days, along with urban kinematic data, were collected to validate the proposed method. Compared with the PAR based on the BSSC, the static experiments demonstrated a reduction of 8.7% and 16.8% in the TTFF and convergence time, respectively. Additionally, the positioning accuracy in the east, north, and up directions was improved by 20.1%, 17.1%, and 4.67%, respectively. Furthermore, the kinematic experiment revealed that the TTFF and convergence time decreased from 1.65 min and 10.5 min to 1.3 min and 1.8 min, respectively, with higher positioning accuracy.

One quarter of the world’s population uses karst groundwater. Due to the complex hydrological conditions in karst areas, they are vulnerable to pollution. The study of the hydrochemical characteristics and environmental quality evaluations of karst groundwater is of great significance for the rational development and utilization of karst groundwater. The study area is located in the Mengzi area of Yunnan Province, which is a typical karst area. The groundwater in the study area was analyzed and evaluated by a statistical analysis, hydrogeochemical analysis, ion ratio and Nemerow’s index method (PN). The results show that the hydrochemical types are mainly the Ca–HCO3 and Ca–Mg–HCO3 types. The main hydrochemical compositions of groundwater were controlled by carbonate dissolution. The results of the water quality evaluation show that the main pollutants in the study area are Mn, COD and NO3−. Compared with groundwater, the concentration and exceeding rate of pollutants in surface water are much higher than those in groundwater. There is the possibility of groundwater pollution by surface water infiltration. The results reveal the characteristics of groundwater pollution in typical karst areas and provide a theoretical basis for the rational development and utilization of groundwater.

Carbon dioxide (CO2) assisted oxidative dehydrogenation of propane over Ga-modified catalysts is highly sensitive to the identity of support, but the underlying cause of support effects has not been well established. In this article, SSZ-13, SSZ-39, ZSM-5, silica and γ-Al2O3 were used to load Ga species by incipient wet impregnation. The structure, textural properties, acidity of the Ga-based catalysts and the process of CO2-assisted oxidative dehydrogenation of propane were examined by X-ray diffraction (XRD), nitrogen physisorption (N2 physisorption), ammonia temperature-programmed desorption (NH3-TPD), pyridine chemisorbed Fourier transform infrared spectra (Py-FTIR), OH-FTIR and in situ FTIR. Evaluation of the catalytic performance combined with detailed catalyst characterization suggests that their dehydrogenation activity is positively associated with the number of acid sites in middle strength, confirming that the Lewis acid sites generated by Ga cations are the active species in the reaction. Ga/Na-SSZ-39(9) also has feasible acidic strength and a unique channel structure, which is conducive to the dissociative adsorption of propane and desorption of olefins. The Ga/Na-SSZ-39(9) catalysts showed superior olefins selectivity and catalytic stability at 600 ℃ compared to any other catalysts. This approach to quantifying support acid strength, and channel structure and applying it as a key catalytic descriptor of support effects is a useful tool to enable the rational design of next-generation CO2-assisted oxidative dehydrogenation catalysts.

The Dempster-Shafer(DS) evidence theory was applied to cooperative spectrum sensing and address the paradox of evidence in classical DS evidence theory, a new weighted distance measure based algorithm was proposed.Firstly, the evidences were extracted for each sensing user.Then, the weighted distance measure of extracted basic probability assignment data was adopted as the similarity between evidences of sensing users.Finally, the similarity of evidences was transformed into credibility, which was utilized as the weight to obtain the weighted average of basic probability assignment.In order to reduce the amount of data reported to the fusion center, the projection approximation method was employed to adjust the basic probability assignment.Both theoretical analysis and simulation results show that the proposed method can improve the detection performance of spectrum sensing while the paradox of evidence exists.Compared with traditional methods the cooperation overhead is reduced.

With the full operation of the global BeiDou navigation satellite system (BDS-3), positioning performance can be further enhanced by BDS-3 combined with the regional BeiDou navigation satellite system (BDS-2). However, due to satellite signals being out of lock and the limited visibility of satellites, the traditional multi-frequency BDS-2/3 precise point positioning (PPP) model is unable to maintain great positioning performance under urban environmental conditions. In this study, a mixed multi-frequency undifferenced and uncombined (UDUC) BDS-2/3 PPP model is presented to improve the positioning performance under urban environmental conditions by making full use of B1I, B1C, B2I, B2a, and B3I signals from all visible BDS satellites. In this model, BDS satellites with single-, dual-, triple- and quad-frequency observations all can participate in PPP. The static and kinematic experiments were carried out using the mixed multi-frequency UDUC BDS-2/3 PPP model to fully assess the positioning performance under urban environmental conditions with comparisons to the multi-frequency model. The static experiments indicated that the mixed multi-frequency UDUC BDS-2/3 PPP could continuously achieve decimeter-level positioning accuracy at a cut-off elevation angle of 40°, but part of the BDS-3 PPP would lose resolution due to limited visible satellites. Furthermore, the initial kinematic vehicle experiment showed that mixed multi-frequency UDUC BDS-2/3 PPP had better satellite geometry and more observation redundancy than the traditional multi-frequency model. Compared with the traditional multi-frequency BDS-2/3 model, the positioning accuracy of the mixed multi-frequency model was improved by 51.6, 35.5, and 39.1%, respectively, in east, north, and up directions. The convergence time was shortened by 40%.

Dynamic displacement plays an essential role in structural health monitoring. To overcome the shortcomings of displacement measured directly, such as installation difficulty of monitoring devices, this paper proposes a smart reconstruction method, which can realize real-time intelligent online reconstruction of structural displacement. Unlike the existing approaches, the proposed algorithm combines the improved mode superposition methods that is suitable for complex beam structures with the Kalman filtering approach using acceleration and strain data. The effectiveness of the proposed multi-rate data fusion method for dynamic displacement reconstruction is demonstrated by both numerical simulation and model vibration experiment. Parametric analysis shows that the reconstruction error is only 5% when the noise signal to noise ratio is 5 dB, illustrating that the proposed algorithm has excellent anti-noise performance. The results also indicate that both the high-frequency and low-frequency components of the dynamic displacements can be accurately reconstructed through the proposed method, which has good robustness.

A novel method of improving the SO2 absorption performance of sodium citrate (Ci-Na) using sodium humate (HA–Na) as an additive was put forward. The influence of different Ci-Na concentration, inlet SO2 concentration and gas flow rate on desulfurization performance were studied. The synergistic mechanism of SO2 absorption by HA–Na and Ci-Na was also analyzed. The consequence shows that the efficiency of SO2 absorption by Ci-Na is above 90% and the desulfurization time added with the Ci-Na concentration rising from 0.01 to 0.1 mol/L. Both the desulfurization efficiency and time may increase with the adding of HA–Na quality in Ci-Na solution. Due to adding HA–Na, the desulfurization efficiency of Ci-Na increased from 90% to 99% and the desulfurization time increased from 40 to 55 min. Under the optimum conditions, the desulfurization time of Ci-Na can exceed 70 min because of adding HA–Na, which is nearly doubled. The growth of inlet SO2 concentration has little effect on the desulfurization efficiency. The SO2 adsorption efficiency decreases with the increase of inlet flow gas. The presence of O2 improves the SO2 removal efficiency and prolongs the desulfurization time. Therefore, HA–Na plays a key role during SO2 absorption and can dramatically enhance the SO2 adsorption performance of Ci-Na solution.

Abstract The cell range expansion (CRE) is encouraged to be applied in the heterogeneous cellular networks (HCNs), to enhance the capacity by offloading macro users to small cells. However, the enhanced inter-cell interference coordination (eICIC) techniques are supposed to be used for mitigating the strong cross-tier interference suffered by the offloaded users and small cell edge users. To address this, a novel soft frequency reuse (SFR) scheme is adopted in this paper. We analyze multichannel downlink scenarios for the SFR scheme using the tools of stochastic geometry. In consideration of the random resource allocation and practical cell load model, the analytical results of coverage probability and average user rate are derived and validated through Monte Carlo methods. Furthermore, our results can reduce to simple closed-form under reasonable special case for modern urban cellular networks. The main evaluation of the performance in terms of average user rate is presented, and the optimal combination of association bias and parameters of the SFR scheme is also investigated. Numerical results show that the SFR scheme outperforms the frequency resource partitioning (FRP) scheme in any load condition. Moreover, the CRE with SFR scheme can improve the average user rate significantly.

[This corrects the article DOI: 10.1371/journal.ppat.1007253.].

Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin six receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17-induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.

This paper has established a two-dimensional (2D) mathematical model for the generation, growth, and deposition of cigarette total particulate matter (TPM) in the smoldering state. The model has covered the chemical reactions and mass transfer as well as the mechanism of generation, flow, and condensation of particulate matter inside a burning cigarette. Cigarette smoke was generated by puffing under a constant pressure, and the pressure of the filter outlet was −274 Pa. The peak of the concentration of particulate matter was spatially overlapped with the peaks of pyrolysis and oxidation. Pertaining to the cross section of the cigarette at the same axial position, the peak of the diameter of particulate matter along the radial distribution first appeared in the zone near the edge of the cigarette cross section, and then gradually moved to the center of the cigarette with the cigarette smoke moving away from the combustion cone. The maximum number density of particulate matter calculated by the 2D mathematical model at the same axial position of the cigarette and the corresponding particle diameter, as well as the filtration efficiency of the filter rod, are in good accordance with the experimental data reported in previous studies.

This study explored the regenerated performance of activated carbon (AC) as SO2 adsorbent. The optimal conditions of SO2 removal were determined by experiment, and then the adsorption efficiency of AC was studied by a method of thermal regeneration. The characteristics of regenerated AC were analyzed by Brunauer-Emmett-Teller (BET) and Scanning Electron Microscopy (SEM) methods. The test results showed that the most suitable adsorption conditions were using 4 g of activated carbon, 1.65 L/min gas flue rate, and 5% O2. During the ten regenerations, the desulfurization efficiency and sulfur capacity of AC still maintained a high level. The characterization results showed that the increase of material surface area and pore volume were 101 m2 g−1, and 0.13 cm3 g−1, respectively, after the cycles.

Phosphorus recovery from industrial wastewater has attracted considerable interest. In this study, struvite crystallization method has been used for treatment of high phosphorus wastewater. The new combination agents of Mg5(CO3)4(OH)2·4H2O and NH4Cl were used as the precipitant. The effects of initial pH, n(Mg):n(P), n(N):n(P), and reaction time on the removal of total phosphorus (TP) in wastewater were investigated. The results showed that under the condition of initial pH = 4, Mg:N:P = 1.2:1.1:1, reaction time for 30 min, and static storage for 20 min, the residual amount of TP in wastewater was 2.98 mg /L, and the removal rate of TP reached 99.99%. The mass fraction of P2O5 in the generated sediment reached 25.22%, equivalent to high grade phosphate ore and slow-release fertilizer, so as to realize the recycling and utilization of phosphorus in ultra-high phosphorous wastewater. This work will have practical application potential in treatment of high phosphorus wastewater and environmental management.

Photodegradation of gas phase benzene by SnO2 nanoparticles has been studied in humid air, dry air and N2 by using a tubular photoreactor. The SnO2 nanoparticles are synthesized by the oxidation of anhydrous stannic chloride (SnCl4) in a propane/air turbulent flame. Direct hole oxidation and the ·OH radical mechanisms have been discussed based on experimental results. The goal of this research is to explore a viable and efficient alternative photocatalyst and photocatalytic process, in particular, for humidity-tolerant photocatalyst or photocatalytic process in environmental applications.

Shugoshin-1 (Sgo1) protects the integrity of the centromeres, and H2A phosphorylation is critical for this process. The mitotic checkpoint kinase Bub1, phosphorylates H2A and ensures fidelity of chromosome segregation and chromosome number. Oncogenic KSHV induces genetic alterations through chromosomal instability (CIN), and its essential antigen LANA regulates Bub1. We show that LANA inhibits Bub1 phosphorylation of H2A and Cdc20, important for chromosome segregation and mitotic signaling. Inhibition of H2A phosphorylation at residue T120 by LANA resulted in dislocation of Sgo1, and cohesin from the centromeres. Arrest of Cdc20 phosphorylation also rescued degradation of Securin and Cyclin B1 at mitotic exit, and interaction of H2A, and Cdc20 with Bub1 was inhibited by LANA. The N-terminal nuclear localization sequence domain of LANA was essential for LANA and Bub1 interaction, reversed LANA inhibited phosphorylation of H2A and Cdc20, and attenuated LANA-induced aneuploidy and cell proliferation. This molecular mechanism whereby KSHV-induced CIN, demonstrated that the NNLS of LANA is a promising target for development of anti-viral therapies targeting KSHV associated cancers.

Kaposi’s sarcoma associated herpesvirus (KSHV), like other human herpes viruses, establishes a biphasic life cycle referred to as dormant or latent, and productive or lytic phases. The latent phase is characterized by the persistence of viral episomes in a highly ordered chromatin structure and with the expression of a limited number of viral genes. Latency Associated Nuclear Antigen (LANA) is among the most abundantly expressed proteins during latency and is required for various nuclear functions including the recruitment of cellular machineries for viral DNA replication and segregation of the replicated genomes to daughter cells. LANA achieves these functions by recruiting cellular proteins including replication factors, chromatin modifying enzymes and cellular mitotic apparatus assembly. LANA directly binds to the terminal repeat region of the viral genome and associates with nucleosomal proteins to tether to the host chromosome. Binding of LANA to TR recruits the replication machinery, thereby initiating DNA replication within the TR. However, other regions of the viral genome can also initiate replication as determined by Single Molecule Analysis of the Replicated DNA (SMARD) approach. Recent, next generation sequence analysis of the viral transcriptome shows the expression of additional genes during latent phase. Here, we discuss the newly annotated latent genes and the role of major latent proteins in KSHV biology.

The latent EBV nuclear antigen 3C (EBNA3C) is required for transformation of primary human B lymphocytes. Most mature B-cell malignancies originate from malignant transformation of germinal center (GC) B-cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is Bcl6, a key regulator of this process. We now demonstrate that EBNA3C contributes to B-cell transformation by targeted degradation of Bcl6. We show that EBNA3C can physically associate with Bcl6. Notably, EBNA3C expression leads to reduced Bcl6 protein levels in a ubiquitin-proteasome dependent manner. Further, EBNA3C inhibits the transcriptional activity of the Bcl6 promoter through interaction with the cellular protein IRF4. Bcl6 degradation induced by EBNA3C rescued the functions of the Bcl6-targeted downstream regulatory proteins Bcl2 and CCND1, which resulted in increased proliferation and G1-S transition. These data provide new insights into the function of EBNA3C in B-cell transformation during GC reaction, and raises the possibility of developing new targeted therapies against EBV-associated cancers.

Spectrum sensing plays an essential role in the detection of unused spectrum whole in cognitive radio networks, including cooperative spectrum sensing (CSS) and independent spectrum sensing. In cognitive radio ad hoc networks (CRAHNs), CSS enhances the sensing performance of cognitive nodes by exploring the spectrum partial homogeneity and fully utilizing the knowledge of neighboring nodes, e.g., sensing results and topological information. However, CSS may also open a door for malicious nodes, i.e., spectrum sensing data falsification (SSDF) attackers, which report fake sensing results to deteriorate the performance of CSS. Generally, the performance of CSS has an inverse relationship with the fraction of SSDF attackers. On the contrary, independent spectrum sensing is robust to SSDF attacks. Therefore, it is desirable to choose a proper sensing strategy between independent sensing and collaborative sensing for CRAHNs coexisting with various fractions of SSDF attackers. In this paper, a novel algorithm called Spectrum Sensing Strategy Selection (4S) is proposed to select better sensing strategies either in a collaborative or in an independent manner. To derive the maximum a posteriori estimation of nodes’ spectrum status, we investigated the graph cut-based CSS method, through which the topological information cost function and the sensing results cost function were constructed. Moreover, the reputation value was applied to evaluate the performance of CSS and independent sensing. The reputation threshold was theoretically analyzed to minimize the probability of choosing the sensing manner with worse performance. Simulations were carried out to verify the viability and the efficiency of the proposed algorithm.

Epstein-Barr virus (EBV) is considered a ubiquitous herpesvirus with the ability to cause latent infection in humans worldwide. EBV-association is evidently linked to different types of human malignancies, mainly of epithelial and lymphoid origin. Of interest is the EBV nuclear antigen 3C (EBNA3C) which is critical for EBV-mediated immortalization. Recently, EBNA3C was shown to bind the E2F1 transcription regulator. The E2F transcription factors have crucial roles in various cellular functions, including cell cycle, DNA replication, DNA repair, cell mitosis, and cell fate. Specifically, E2F6, one of the unique E2F family members, is known to be a pRb-independent transcription repressor of E2F-target genes. In our current study, we explore the role of EBNA3C in regulating E2F6 activities. We observed that EBNA3C plays an important role in inducing E2F6 expression in LCLs. Our study also shows that EBNA3C physically interacts with E2F6 at its amino and carboxy terminal domains and they form a protein complex in human cells. In addition, EBNA3C stabilizes the E2F6 protein and is co-localized in the nucleus. We also demonstrated that both EBNA3C and E2F6 contribute to reduction in E2F1 transcriptional activity. Moreover, E2F1 forms a protein complex with EBNA3C and E2F6, and EBNA3C competes with E2F1 for E2F6 binding. E2F6 is also recruited by EBNA3C to the E2F1 promoter, which is critical for EBNA3C-mediated cell proliferation. These results demonstrate a critical role for E2F family members in EBV-induced malignancies, and provide new insights for targeting E2F transcription factors in EBV-associated cancers as potential therapeutic intervention strategies.

Studies have suggested that Epithelial-Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas.

Pedestrian-positioning technology based on the foot-mounted micro inertial measurement unit (MIMU) plays an important role in the field of indoor navigation and has received extensive attention in recent years. However, the positioning accuracy of the inertial-based pedestrian-positioning method is rapidly reduced because of the relatively low measurement accuracy of the measurement sensor. The zero-velocity update (ZUPT) is an error correction method which was proposed to solve the cumulative error because, on a regular basis, the foot is stationary during the ordinary gait; this is intended to reduce the position error growth of the system. However, the traditional ZUPT has poor performance because the time of foot touchdown is short when the pedestrians move faster, which decreases the positioning accuracy. Considering these problems, a forward and reverse calculation method based on the adaptive zero-velocity interval adjustment for the foot-mounted MIMU location method is proposed in this paper. To solve the inaccuracy of the zero-velocity interval detector during fast pedestrian movement where the contact time of the foot on the ground is short, an adaptive zero-velocity interval detection algorithm based on fuzzy logic reasoning is presented in this paper. In addition, to improve the effectiveness of the ZUPT algorithm, forward and reverse multiple solutions are presented. Finally, with the basic principles and derivation process of this method, the MTi-G710 produced by the XSENS company is used to complete the test. The experimental results verify the correctness and applicability of the proposed method.

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers.

We analyze the competitive price game model for spectrum sharing in cognitive radio networks with multiple primary users and secondary users and propose a user requirement based competitive price game model for the calculation of the shared spectrum size of cognitive user in Bertrand game. The communication requirement of the cognitive user is quantified into different requirement levels. With the application of spectrum requirement factor, cognitive user can adjust the demanded shared spectrum size according to self-requirement level and the shared spectrum price provided by licensed users. It can avoid the waste of spectrum resource caused by the overdistribution of spectrum to the cognitive user with low communication requirement. Simulation results show that the occupied spectrum of cognitive user can be adjusted with the variation of requirement levels, and the licensed users can achieve better profit performance with consideration of requirement of cognitive user by adjustment of the shared spectrum price proposed spectrum sharing model.

Component doping is the fundamental topic for modulating the properties of semiconductor materials. The introduction of doping ions into lead halide perovskites (LHPs) can not only maintain the excellent photoelectric properties but also enhance the stability of LHPs in open air and thermal environments. However, due to the "self-purification" effect in crystallography, there is an inherent trend to pop doping ions out of LHPs lattice. In this work, it is confirmed that in Mn2+ doped LHPs nanocrystals (NCs) the discharge of Mn2+ will be accelerated at higher temperatures. It is also proved that even at room temperature, the dopants in LHPs NCs will also actively "migrate", resulting in declined optical performance. Therefore, for cation alloying/doping LHPs NCs, the migration of doping ions in the material should be considered in addition to the intrinsic halide migration characteristics. This work will provide a benign reference for application of doped LHPs NCs. [ABSTRACT FROM AUTHOR]

In the new era, there is an urgent need to further promote pairing assistance to Tibet, promote the simultaneous construction of a strong agriculture in China, and compose a Chinese-style modernization. Southern Tibet, located in the southeastern part of the Tibet Autonomous Region, includes Shannan City and Nyingchi City, is a region assisted by four provincial partners including Hubei Province. This paper introduces the agricultural environment in southern Tibet, studies its agricultural characteristics, and analyzes the main issues of its pairing assistance. Taking forging the strong consciousness of the Chinese national community as the main line, the paper explores strategies for promoting agricultural high-quality development in southern Tibet through pairing assistance to Tibet from the perspective of agricultural power, and proposes some strategies, such as inheriting agricultural cultural heritage, promoting the upgrading of modern seed industry, enhancing the characteristic advantages of highland barley (naked barley) and animal husbandry industries, and developing edible fungi and cold water fish industries. [ABSTRACT FROM AUTHOR]

Establishing the Greater Food Approach and promoting the Yangtze River Economic Belt's national major regional development strategy can better support and serve the agricultural power and Chinese-style modernization. This paper introduces the characteristics of fruit industry in 16 autonomous prefectures and 47 autonomous counties under the jurisdiction of the Yangtze River Economic Belt. It studies the intellectual property resources of brand marks from the aspects of geographical indications, collective trademarks, certification trademarks, well-known trademarks in China and national design patents, and analyzes the main problems of brand and high-quality development of fruit industry in these ethnic autonomous areas. Finally, it puts forward some strategies, such as improving the protection of intellectual property rights of geographical indications, using intellectual property rights of brand signs, building modern seed industry upgrading project, drawing lessons from the experience of thousand villages demonstration project, ensuring that large-scale poverty does not occur, and building a diversified food supply system. [ABSTRACT FROM AUTHOR]