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Though using parallel evolutionary algorithm to solve large-scale TSP problems is efficient, the parallel computer costs too much and the algorithm is not easy to expand. To address this issue, I propose a parallel genetic algorithm based on a gene pool under the existing network. To replace the group-genes in the evolutionary algorithm with the genes from the gene pool, the algorithm conducts greedy algorithm. The host process conducts greedy algorithm and improved evolutionary algorithm of Inver-over operator while the child process performs the improved hybrid genetic algorithms. Simulation results demonstrate that this algorithm achieves a better solution.

This paper examines revenue and expenditure management in the People’s Republic of China (PRC) and recommends ways to cut risk and strengthen the resilience of the fiscal system. The paper outlines the PRC’s fiscal reforms and the impact of COVID-19. It notes the financing gap facing subnational governments that play a key role in providing public investment in infrastructure. The authors discuss the PRC’s need to adjust its focus on economic growth to tackle its fiscal imbalance, improve the sustainability of local government finances, and address inequality and environmental degradation. This paper is the first of two on key aspects of fiscal reform in the PRC.

Objectives: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used. Methods: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n=53) were matched at a ratio of 1 to 2 (n=106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient’s prognosis of the two groups were compared. Results: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P=0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P=0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P=0.024). However, there were no significant differences in ICU mortality or 28-day mortality. Conclusions: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients.

To evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) in detecting pathogens in bronchoalveolar lavage fluid (BALF) for pulmonary infection in solid organ transplant patients in intensive care unit (ICU).A retrospective study was conducted, the BALF samples from 46 patients with post organ transplant pneumonia/suspected pneumonia admitted to the Department of Critical Care Medicine of the First Affiliated Hospital of University of Science and Technology of China from August 2018 to August 2021 were collected, all tested by simultaneous mNGS and conventional comprehensive microbial test (CMT), and the results of CMT were used as the reference standard to compare the differences in the diagnostic value of mNGS and CMT for pulmonary infections in solid organ transplant patients, and to analyze the diagnostic value of mNGS for mixed infections.(1) Pneumonia pathogens: a total of 31 pathogens were detected in 35 patients, including bacteria (16 species), fungi (9 species) and viruses (6 species). Among them, 25 pathogens were detected by mNGS and CMT, and only 19 pathogens were detected by mNGS. Among the microorganisms isolated by mNGS method, the detection rates of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were higher [51.4% (18/35), 42.9% (15/35), 31.4% (11/35), respectively]; Candida albicans, Aspergillus and Pneumocystis carinii were the most commonly detected fungi [31.4% (11/35), 22.9% (8/35), 22.9% (8/35), respectively]; 20 patients were positive for the virus, and the most commonly detected viruses were cytomegalovirus, herpesvirus and EB virus [28.6% (10/35), 20.0% (7/35), 17.1% (6/35), respectively]. In addition, one case of Brucella was detected by mNGS. (2) Diagnostic efficiency: as far as bacterial detection is concerned, 20 cases of negative results were obtained by CMT detection of 35 samples included in the study, and a total of 10 cases of positive results were obtained by mNGS detection of negative samples; the percentage of mNGS positive samples was significantly higher than that of CMT positive samples [odds ratio (OR) = 5.5, 95% confidence interval (95%CI) = 1.2-24.8, P = 0.02]. When compared with CMT, the sensitivity and specificity of mNGS were 93.3% and 50.0%, and the positive predictive value (PPV) and negative predictive value (NPV) were 58.3%, 91.1%. As far as fungal detection was concerned, there was no significant difference in the percentage of positive samples between the two methods (OR = 1.5, 95%CI = 0.5-4.2, P = 0.60); the sensitivity and specificity of mNGS were 72.2% and 64.7%, and the PPV and NPV were 68.4%, 68.8%; CMT test of the 35 included samples produced 17 negative results, and mNGS test of the negative samples produced 6 positive results. A total of 20 patients tested positive for the virus by mNGS. In addition, 23 patients (65.7%) were diagnosed with pulmonary mixed infection.The use of mNGS to detect pathogens in BALF can improve the sensitivity and specificity of bacterial identification of pulmonary infection in critically ill organ transplant patients, and mNGS has obvious advantages in detecting virus and identifying mixed infections.

OBJECTIVE: To explore the perioperative period characteristics of paediatric cochlear implant recipients of CHARGE syndrome with complex deformities. METHODS: Retrospective case series of CHARGE syndrome were included. Radiological results, intraoperative findings, surgical planning and post-operative complications were analyzed. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre and post-operatively to measure auditory speech rehabilitation outcomes. RESULTS: Five prelingual profoundly deaf children were identified, aged from 14 months to 60 months. All patients had congenital heart disease and underwent surgery before cochlear implantation. Upper airway abnormalities were detected as choanal atresia, laryngomalacia and tracheal stenosis. All ten ears showed cochlear abnormalities(Incomplete partition Ⅱ), eight of them combined with secretory otitis media and/or middle ear deformity. All patients underwent single side surgery using standard transmastoid facial recess approach. Full insertion of the electrode was achieved in two cochleas, while partial insertion was done in three cochleas. Three ears with absent auditory nerves in MRI showed no response in the neural remote test. All patients had improved audio-speech performance with CAP scores 3.0±0.7 and 3.6±0.9, SIR scores 1.2±0.4 and 1.8±0.8, IT-MAIS scores 18.8±9.1 and 26.2±10.0, MUSS scores 2.2±2.4 and 7.2±8.3 after twelve months and twenty-four months follow up. CONCLUSION: Cochlear implantation in patients with CHARGE syndrome is a challenge in both its surgical and rehabilitation aspects due to multiple abnormalities. Adequate treatment planning is necessary for safe and effective surgery, including airway structures and intricate temporal bone landmarks.

The metastasis of nasopharyngeal carcinoma (NPC) is a complex process associated with oncogenic dysfunction, the deciphering of which remains a challenge and requires more in-depth studies. Y-box protein 3 (YBX3) is a DNA/RNA binding protein associated with gene transcription, DNA repair, and the progression of various diseases. However, whether and how YBX3 affects the metastasis of NPC remains unknown. Thus, in this study, we aimed to investigate the role of YBX3 in the metastasis of NPC and determine its underlying mechanism. Interestingly, it was found that the expression of YBX3, which was associated with NPC metastasis, was upregulated in the clinical NPC tissues and cell lines. Moreover, we found that knockdown of YBX3 expression by lentivirus shRNA significantly suppressed NPC cells migration in vitro and metastasis in vivo. Mechanistically, RNA sequencing results suggested that the genes regulated by YBX3 were significantly enriched in cell adhesion molecules, cAMP signaling pathway, calcium signaling pathway, focal adhesion, PI3K/AKT signaling pathway, Ras signaling pathway, Rap1 signaling pathway, NF-κB signaling pathway, and Chemokine signaling pathway. Of these, PI3K/AKT signaling pathway contained the most genes. Accordingly, YBX3 knockdown decreased the activation of PI3K/AKT signaling pathway, thereby inhibit epithelial-to-mesenchymal transition (EMT) and MMP1. These results have demonstrated that YBX3 are involved in the metastasis of NPC through regulating PI3K/AKT signaling pathway, and serve as a potential therapeutic target for patients with NPC.

Colorectal cancer (CRC) is the third most common cancer in the world and its development is associated with oncogenic dysfunction. Therefore, the present study aimed to identify differentially expressed genes (DEGs) in CRC tissues and to determine the role of keratin 80 (KRT80) in CRC cell proliferation. DEGs were initially screened in 32 paired CRC tissues and matched adjacent normal tissues from RNA-Seq datasets in The Cancer Genome Atlas database using the limma package in R software. In total, 2,114 DEGs were identified, of which KRT80 was discovered to be the most upregulated in CRC tissues. Moreover, increased KRT80 expression levels were confirmed in tissues collected from 50 patients with CRC using reverse transcription-quantitative PCR, and its increased expression levels were significantly associated with increased lymph node and distant metastasis and a higher pathological stage. Furthermore, KRT80 knockdown using siRNA decreased the viability and proliferation of CRC cells. Finally, pathway analysis revealed that the proteins co-expressed with KRT80 in CRC were enriched in the cell cycle, DNA replication, immune system, metabolism of protein and RNA, signal transduction and other cellular processes. Among them, the cell cycle and DNA replication pathways contained the highest number of the proteins identified. In conclusion, the findings of the present study suggested that KRT80 may be overexpressed in CRC tissues. Furthermore, KRT80 may be involved in the proliferation of CRC cells, which is likely through its ability to regulate the cell cycle and DNA replication pathways, thus it may serve as a potential therapeutic target for patients with CRC.

BACKGROUND: Circular RNAs (circRNAs) are endogenous RNAs that have a covalent closed cycle configuration. circRNAs have been found to be differentially expressed in many human cancers. Therefore, circRNAs may be ideal biomarkers for the diagnosis and treatment of cancer. However, we know very little about the function of circRNAs in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the circRNA expression profiles in NPC. METHODS: We utilized high-throughput RNA sequencing (RNA-Seq) to evaluate the circRNA expression profile in NPC A total of 13,561 unique circRNA candidates were detected. Selection of aberrantly expressed circRNAs was carried out using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. We carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to identify the biological functions of differentially expressed circRNAs. Moreover, bioinformatics analyses were implemented to predict the effects between circRNAs and cancer-related microRNAs (miRNAs), and we used Cytoscape to build a cancer-related circRNA-miRNA target gene map. Finally, to verify dysregulated circRNAs, quantitative real-time PCR was utilized. RESULTS: In NPC tissues, we found that 73 circRNAs were downregulated and 59 were upregulated. The top 12 candidate circRNAs were selected from several vital NPC pathways such as the human papillomavirus and Epstein-Barr virus infection signaling pathways (hsa05165 and hsa05169, respectively), Hepatitis B (hsa05161), and the Ras signaling pathway (hsa04014). A network map of circRNA-miRNA interactions of 12 differentially expressed circRNAs was built. Hsa_circ_0007637 expression distinguished NPC tissues from paired healthy tissues and NPC cell lines (HNE1 6-10B, 5-8F, CNE-2, and so on) from a normal epithelial (NP460) cell line. CONCLUSIONS: In this study, we investigated the profiles of differentially expressed circRNAs in NPC, and our results show that hsa_circ_0007637 may be a biomarker for NPC and play a role in its development. This observation-based research identified dysregulated circRNAs in NPC, which may assist in the development of biomarkers for this disease. Further studies on the mechanisms and functions of these circRNAs may promote our understanding of NPC tumorigenesis.

Objective To explore the applicability of metagenomic next-generation sequencing (mNGS) technology for the detection of blood pathogens in intensive care unit patients. Methods The clinical data of 63 critically ill patients who could not be diagnosed with blood culture (BC) and who underwent mNGS blood sample testing were retrospectively analyzed. The diagnostic efficacy of mNGS was compared with that of traditional detection methods; the distribution of the pathogens identified by mNGS was analyzed; and the differences in laboratory tests, comorbidities, treatment, and prognosis between the mNGS-positive and mNGS-negative groups were compared. Results The positive rate of mNGS was 41.3% (26/63), and 16 patients were found to have mixed infections. However, the positive rate of BCs performed simultaneously with mNGS was only 7.9% (5/63). The results of univariate analysis showed that the average length of intensive care unit stay (β, −8.689 [95% CI, −16.176, −1.202]; P = 0.026) and the time from onset to sequencing (β, −5.816 [95% CI,−9.936, −1.696]; P = 0.007) of the mNGS-positive group were significantly shorter than those of the mNGS-negative group. More patients in the positive group were adjusted for anti-infective treatment after mNGS (OR, 3.789 [95% CI,1.176, 12.211]; P Conclusions Detection of blood pathogens by mNGS has good applicability for critically ill patients who cannot be diagnosed by BC in the early stages of infection, and mNGS should be performed as early as possible to obtain higher pathogen detection rates.

Background: Aberrant overexpression of Bcl-2 protein has been detected in 80% of nasopharyngeal carcinoma (NPC), and Bcl-2 family proteins are implicated in both NPC oncogenesis and chemotherapy resistance. Previous studies have shown that while treatment of NPC cells with Bcl-2 family inhibitors alone is rarely effective, concomitant treatment with a cytotoxic reagent such as cisplatin can increase efficacy through a synergistic effect. The aim of the current work was to determine how we might increase the efficacy of Bcl-2 family inhibitors in the absence of cytotoxic reagents, which are associated with negative side effect profiles. Methods: We assessed cell proliferation in Bcl-2 high-expressing NPC cells by CCK-8 assay after treatment with the Bcl-2 inhibitor ABT-199 and/or the Mcl-1 inhibitor 563845. Apoptotic induction by ABT-199 was evaluated by Annexin V-FITC and P1 double staining. We also evaluated Bcl-2 family protein expression (Bim, Mc1-1, Bcl-xL, Noxa) after treatment with ABT-199 by western blotting. Finally, xeno-grafted Balb/c nude mice were used to test ABT-199 efficacy in vivo, H&E and immunohistochemistry assay were used to analyze tumor samples. Results: ABT-199 effectively induced NPC cell apoptosis in vitro and in the xenograft model. Following ABT-199 treatment in NPC cells, upregulation of Mcl-1 and Bcl-xL can lead to drug resistance, while concomitant Noxa overexpression partially neutralized the Mcl-1-caused resistance. Given that ABT-199 induces apoptosis in NPC cells through the Bcl-2/Noxa/Mcl-1 axis, treatment avenues further targeting this pathway should be promising. Indeed, the newly developed Mcl-1 inhibitor 563845 in combination with ABT-199 had a synergistic effect on NPC cell apoptosis. Conclusion: Bcl-2 inhibition in NPC cells with ABT-199 triggers apoptosis through the Bcl-2/Noxa/Mcl-1 axis, and dual inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Mcl-1 provided a strong synergistic effect without the need for adjunctive cytotoxic agent treatment with cisplatin. (C) 2018 Elsevier Inc. All rights reserved.

Background The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. Methods We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. Results In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. Conclusions A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

A (2-SPS/PU)&R 4-DOF hybrid robot for ankle rehabilitation is presented in this paper. The robot is able to generate three-dimensional rotations and a stretching motion along the lower limb direction for ankle rehabilitation. In the paper, the inverse kinematics of the parallel mechanism is analyzed using closed-loop vector method. The velocity Jacobian matrix of the parallel mechanism is solved. The kinematics of the (2-SPS/PU)&R hybrid mechanism is simulated using ADAMS software. The results show that the mechanism can reach the motion ranges needed for ankle joint rehabilitation.

Rationale Catheter-related thrombosis is a serious complication of lung transplantation under venovenous extracorporeal membrane oxygenation (ECMO). Although ECMO-related thrombosis is not uncommon, there are few reports of giant hollow catheter thrombosis in lung transplantation under venovenous ECMO (ECMO). Blood loss and transfusion of coagulation factors may promote ECMO-related thrombosis. Hollow catheter thrombus was not detected on ultrasonography performed after initiation of ECMO. Therefore, it is essential to identify, manage, and reduce or avoid such thrombosis. Patient concerns We report a rare case of a 43-year-old man with advanced silicosis who developed a massive hollow catheter thrombus during lung transplantation. Anticoagulant therapy did not affect the size of the thrombus. Diagnosis Giant hollow catheter thrombosis was diagnosed by ultrasonography. Thrombosis from the right external iliac vein to the inferior vena cava was found in the shape of the ECMO pipe. Interventions Heparin was prescribed as an anticoagulant. Outcomes Anticoagulant therapy did not affect the size of the thrombus during 2 weeks. The patient developed an infection and died of multiple organ failure. Conclusion It is uncommon for massive hollow thrombus to occur during venovenous-ECMO-assisted lung transplantation. Fibrinogen and prothrombin complexes promote the formation of thrombus, and the measurement of the wall thickness of ECMO catheter may help to detect such thrombus.

In this paper, two average tungsten carbide particle sizes of 2, 0.5 μm are placed respectively, in contact with a WC-16Co substrate, pressed at the pressure of 4.5–5.5 GPa, and heated to temperatures ranging from 1350°C to 1500°C in a large-volume cubic press. During the process Co was forced out of the WC-16Co substrate into the compressed powder. The resulting infiltrated samples were characterized using X-ray diffraction (XRD), scanning electron microscope (SEM), Vickers hardness and cutting performance tests. The results of XRD confirmed that the sintered bulks have WC and Co phases. The scanning electron microscopy (SEM) analysis reveals that the WC grains in well-sintered alloys are round in shape and cobalt with lower content is uniformly dispersed in the WC grain boundaries. The sintered sub-micron WC-Co alloy with a cobalt content of 3.8 wt% exhibits a prominent combination of high hardness value of 23.1 GPa and a large fracture toughness value of 8.6 MPa m½. The high-speed cutting tests...

Background Intake of trans fatty acids (TFAs) from partially hydrogenated vegetable oil is associated with a variety of adverse outcomes, but little is known about the health effects of ruminant trans fats. Trans-vaccenic acid (TVA) is a naturally occurring TFA found in the fat of ruminants and in human dairy products. The present study was conducted to investigate the anticancer activity and underlying mechanisms of TVA on human nasopharyngeal carcinoma (NPC) 5-8F and CNE-2 cells. Methods A CCK8 assay was used to determine the effect of TVA and the Mcl-1 inhibitor S63845 on the proliferation of NPC cells. Apoptosis was measured using flow cytometry. Western blotting was used to detect the protein expression levels of factors associated with Bcl-2-family protein signaling and Akt signaling. Results TVA significantly inhibited cell proliferation in a dose-dependent manner. Mechanistic investigation demonstrated that TVA significantly decreased p-Akt levels and Bad phosphorylation on Ser-136 and Ser-112. More importantly, we discovered that the Mcl-1 inhibitor S63845 synergistically sensitized NPC cells to apoptosis induction by TVA. Conclusion TVA can inhibit NPC cell growth and induced apoptosis through the inhibition of Bad/Akt phosphorylation. The combined use of TVA and Mcl-1 inhibitors offers a potential advantage for nasopharyngeal cancer treatment.

Trust is a very important criterion when service customers select desired Web services from a cluster of Web services with the same function. Most existing trust models cannot effectively implement personalized service selection with regard to consumer preferences and expectations. This paper designs a novel trust management method based on peer-to-peer network and presents a customer-centric trust evaluation model for personalized service selection. The trust evaluation model firstly maintains consumer-to-consumer trust values that are calculated according to preference similarity between customers, secondly gathers ratings on services submitted by other consumers, then synthesizes customer-to-customer trust and these ratings to generate personalized consumer-to-service trust, and finally selects the desired services according to the expected trust levels presented by customers. This paper conducts some experiments to demonstrate the details of service selection. Experimental results show that this model has good applicability to implement personalized service selection. The proposed model well simulates the reality.

Phosphatidylserine (PS) and docosahexaenoic acid-phosphatidylserine (DHA-PS) have significant nutritional and biological functions, which are extensively used in functional food industries. Phospholipase D (PLD)-mediated transphosphatidylation of phosphatidylcholine (PC) or DHA-PC with l-serine, is an effective method for PS and DHA-PS preparation. However, because of the hydrolysis activity of PLD, PC and DHA-PC would be converted to the undesirable byproduct, phosphatidic acid (PA) and DHA-PA. In this study, a novel phospholipase D (PLDa2) was firstly cloned from Acinetobacter radioresistens a2 with high transphosphatidylation activity and no hydrolysis activity. In the PLD-catalyzed synthesis process (12h), both the transphosphatidylation conversion rate and selectivity of PS and DHA-PS were about 100%, which is the only PLD enzyme reported with this superiority up till now. In comparison with the majority of other known PLDs, PLDa2 exerted the highest activity at neutral pH, and it was stable from pH 4.0 to pH 9.0. In addition, PLDa2 had excellent thermal stability, with an optimum reaction temperature of 40°C and keeping more than 80% activity from 20°C to 60°C. The high catalytic selectivity mechanism of PLDa2 was explained by utilizing homology modeling, two-step docking, and binding energy and conformation analysis. PLDa2 ensured a stable supply of the biocatalyst with its most preponderant transphosphatidylation activity and PS selectivity, and had great potential in phospholipids industrial production.

Skewed T helper 2 (Th2)‑cell polarization plays a critical role in the pathogenesis of allergic inflammations; however, the underlying mechanisms require further elucidation. The aim of the present study was to investigate the mechanisms through which the interaction between T‑cell immunoglobulin and mucin domain (TIM)4 and TIM1 regulates the expression of silent information regulator 1 (SIRT1) in Th2 cells, and the role of SIRT1 in Th2‑cell polarization during nasal allergic inflammation. The results demonstrated that TIM4 expression by splenic dendritic cells was increased in mice with allergic rhinitis, and the TIM4TIM1 interaction promoted CD4+ T cells to express SIRT1 during allergic inflammation via enhancing phosphoinositide 3‑kinase/Akt phosphorylation. SIRT1 then facilitated CD4+ T‑cell proliferation through downregulating the expression of Fas ligand, caspase-3 and p53 in mice with nasal allergic inflammation. In conclusion, the interaction of TIM4TIM1 was found to promote Th2‑cell proliferation through enhancing SIRT1 expression in mice with nasal allergic rhinitis.

c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3β. We find that hnRNPK is able to inhibit the Ser9 phosphorylation of GSK3β by PKC. This has the effect of activating GSK3β and thereby stabilizing c-FLIP protein which contributes to the resistance to TRAIL in H1299 cells. Our immunohistochemical analysis using tissue microarray provides the clinical evidence of this finding by establishing a negative correlation between the level of hnRNPK expression and the Ser9 phosphorylation of GSK3β in both lung adenocarcinoma tissues and normal tissues. Moreover, in all cancer tissues examined, hnRNPK was found in the cytoplasm whereas it is exclusively nuclear in the normal tissues. Our study sheds new insights on the molecular mechanisms governing the resistance to TRAIL in tumor cells, and provides new clues for the combinatorial chemotherapeutic interventions with TRAIL.

Pro-inflammatory cytokines play a critical role in the development of autoimmune and inflammatory diseases. Targeting the cytokine environment has proven efficient for averting inflammation. In this study, we reported that 6-[4-(aminomethyl)-2-chlorophenoxyl]benzo[c][1,2]oxaborol-1(3H)-ol (AN3485), a benzoxaborole analog, inhibited TLR2-, TLR3-, TLR4-, and TLR5-mediated TNF-α, IL-1β, and IL-6 release from human PBMCs and isolated monocytes with IC(50) values ranging from 18 to 580 nM, and the inhibition was mediated at the transcriptional level. Topical administration of AN3485 significantly reduced PMA-induced contact dermatitis and oxazolone-induced delayed-type hypersensitivity in mice, indicating its capability of penetrating skin and potential topical application in skin inflammation. Oral administration of AN3485 showed dose-dependent suppression of LPS-induced TNF-α and IL-6 production in mice with an ED(90) of 30 mg/kg. Oral AN3485, 35 mg/kg, twice a day, suppressed collagen-induced arthritis in mice over a 20-day period. The potent anti-inflammatory activity in in vitro and in vivo disease models makes AN3485 an attractive therapeutic lead for a variety of cutaneous and systemic inflammatory diseases.

Modular innovation network is an organic netlike synergy system according the rules of modularity. In modular innovation system, the loosely coupled knowledge modules can be flexibly recombined to meet the dynamic changes of market demands. This system structures do great benefits for flexible knowledge management in virtue of cutting transaction cost of knowledge collaboration and simplifying the complexity of gigantic knowledge systems. This paper focuses its study on the context of modular innovation network and flexible knowledge management. We first study the meaning and characters of modular innovation network, then we research the mechanism of return increasing mechanism and the mechanism of flexible knowledge management based on modular innovation networks. Then, we analyze four modes of knowledge creating under this mechanism. At last, we play the character analysis of that knowledge management mechanism.

Web service selection, as an important part of Web service composition, has direct influence on the quality of composite service. Therefore, it has attracted many researchers to focus on the research of quality of service (QoS) driven Web service selection in the past years, and many algorithms based on integer programming (IP), mixed integer linear programming (MILP), multi-dimension multi-choice 0-1 knapsack problem (MMKP), Markov decision programming (MDP), genetic algorithm (GA), and particle swarm optimization (PSO) and so on, have been presented to solve it, respectively. However, these results have not been satisfied at all yet. In this paper, a new cooperative evolution (Co-evolution) algorithm consists of stochastic particle swarm optimization (SPSO) and simulated annealing (SA) is presented to solve the Web service selection problem (WSSP). Furthermore, in view of the practical Web service composition requirements, an algorithm used to resolve the service selection with multi-objective and QoS global optimization is presented based on SPSO and the intelligent optimization theory of multi-objective PSO, which can produce a set of Pareto optimal composite services with constraint principles by means of optimizing various objective functions simultaneously. Experimental results show that Co-evolution algorithm owns better global convergence ability with faster convergence speed. Meanwhile, multi-objective SPSO is both feasible and efficient.

Under the open environments, it is very difficult to guarantee the trustworthiness of interacting business process using traditional software engineering methods, at the same time, for dealing with the influence of external factors, some proposed business process mining methods are only effective 1-bounded business process, and some behavior dependent relationships are ignore. A behavior trustworthiness analysis method of business process based on induction information is presented in the paper. Firstly, aimed to the internal factors, we analyze the consistent behavior relativity to guarantee the predictable function. Then, for the external factors, in order to analyze the behavior change of business process, we propose a process mining methods based on induction information. Finally, experiment simulation is given out, and compares our method with genetic process mining methods. Theoretical analysis and experimental results indicate that our method is better than the genetic process mining method.

The essence characteristics of software trustworthiness are software execution effect and behavior can be anticipated, which is an important index of software quality. Under the open and dynamic environments, some uncertainty factors cause the behavior of software to be uncontrolled, uncertainty and unpredictable. Behavioraware networked software trustworthiness research methods are proposed in the paper. Firstly, we propose the analysis methods of the consistency between the inferred specification models with component specification model. Then, for analyzing the component interaction behavior, the behavior relativity analyzing method is presented based on Petri net. Finally, aimed to the outer factors, we analyze the behavioral congruence between theoretical composite models with dynamic behavior model based on running logs. Theoretical analysis and the example analysis indicated that this method is benefit to analyze the trustworthiness of networked software.

With the development of Internet and Web service technology, Web service composition has been an effective way to construct software applications; service selection is the crucial element in the composition process. However, the existing selection methods mostly generate static plans since they neglect the inherent stochastic and dynamic nature of Web services. As a result, Web service composition often inevitably terminates with failure. An indeterminacy-aware service selection algorithmbased on an improved Markov decision process (IMDP) has been designed for reliable service composition, but it suffers from higher computation complexity. Therefore, an efficient method is proposed, which can reduce the computation cost by converting the service selection problem based on IMDP into solving a nonhomogeneous linear equation set. Experimental results demonstrate the success rate of service composition has been improved greatly, whilst also reducing computation cost.

Summary This paper documents the diverging patterns of capital accumulation, profit rates, investment rates, capital productivity, and technological progress of China and India between 1980 and 2003. The two Asian economies have followed very different growth patterns and, today, they face different challenges. India’s is how to accelerate growth, while China’s policy makers debate between the need to maintain a high growth rate to generate employment and the imperative to reduce it to cool the economy. India must address impediments to investment. China must deal with the question of whether investment can continue being the main source of growth.

The Dermatophagoides farina (D. farina) allergens are an important factor contributing to allergic disease. To identify new allergens is important for diagnosis and treatment of allergic diseases. In this study, we sought to characterize the biological activity of Der f 21 of D. farina. The recombinant Der f 21 protein was characterized by western-blot, ELISA and Skin prick test using clinic patient’s serum.An allergic asthma mouse model was established with the rDer f 21 as a specific antigen. The results showed that the sera from 28.9% in 38 dust mite allergic children displayed positive results in response to rDer f 21, and 42% in 98 dust mite allergic patients displayed positive response in skin prick test. In addition, Immune inhibition assays showed there was IgE cross-reactivity between rDer f 21 and rDer f 5. Moreover, an allergic asthma mouse model was established. Airway hyperresponsiveness, serum specific IgE, IgG1, eosinophil infiltration in the allergic mice, interleukin-4(IL-4) and interferon-γ (INF-γ) from spleen cells were markedly increased in the allergic mice. The results demonstrate that Der f 21 is a novel allergen.