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Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved., Graphical abstract Image 1, Highlights • The PDA-ALN-DOX presented high bone targeting property, photothermal conversion efficiency, drug loading capacity, and multimodal imaging modalities. • CPT is a more efficient and convenient therapy for bone tumors.

Background: Subthreshold depression (SD) is considered to be the precursor stage of major depression, which is correlated with functional impairment and increased suicide rate. Although there are multiple therapies for the treatment of SD, the comparison and efficacy of various methods has yet to be evaluated. This study aimed to evaluate the efficacy of different therapies by performing a Bayesian network meta-analysis. Methods: We searched eight databases on April 3, 2021. Center for Epidemiologic Studies Depression Scale (CES-D), Beck Depression Inventory scale (BDI), the Patient Health Questionnaire-9 (PHQ-9), and the Kessler Screening Scale for Psychological Distress (K-6) were used as efficacy outcomes. This Bayesian network meta-analysis used a fixed-effects model. Findings: Twenty-one randomized controlled trials involving 5,048 participants were included in this study. The results suggested that electroacupuncture (MD −12.00, 95% CrI −15.00, −10.00), conventional acupuncture plus wheat-grain moxibustion (MD −9.70, 95% CrI −14.00, −5.30), and the Chinese traditional peripateticism pill plus group counseling (MD −9.00, 95% CrI −11.00, −6.70) had better efficacy than the control group (CG) in improving CES-D. For BDI outcome, bright light therapy (MD −9.70, 95% CrI −13.00, −6.00), behavioral activation program (MD −5.70, 95% CrI −6.10, −5.40), and dim light therapy (MD −6.30, 95% CrI −10.00, −2.20) were better than the CG. Tai chi (MD −3.00, 95% CrI −4.00, −2.00) was better than CG for PHQ-9 outcomes. Telephone-based cognitive behavioral treatment (MD −2.50 95% CrI −2.70, −2.30) was better than the CG for K-6 scores. Conclusion: Our results suggest that electroacupuncture or bright light therapy appear to be the better choices in the treatment of SD. This study provide new insights into clinical treatment selection and may aid the development of guidelines for the management of SD., Graphical Abstract Graphical abstract of the network meta-analysis. Note: CES-D, Center for Epidemiologic Studies Depression Scale; BDI, Beck Depression Inventory Scale; PHQ-9, the nine-Item Patient Health Questionnaire; K6, Kessler Screening Scale for Psychological Distress; SUCRA, surface area under the cumulative ranking curves.

Background Highly pathogenic H5N1 influenza viruses remain a pandemic risk to the world population. Although vaccines are the best solution to prevent this threat, a more effective vaccine for H5 strains of influenza has yet to be developed. All existing vaccines target only serum antibody against influenza as the primary outcome, while mucosal immunity has not been addressed. To address these shortcomings we have used an effective mucosal adjuvant system to produce a prototype vaccine that provides antibody, cellular and mucosal immunity to multiple serotypes of H5. Methods Plant-derived recombinant H5 (rH5) antigen was mixed with a novel nanoemulsion NE01 adjuvant. The rH5-NE01 vaccine was administered intranasally to CD-1 mice and ferrets. Immunogenicity of this immunization was evaluated through rH5-specific antibody and cellular immune responses. Hemagglutination inhibition (HI) and virus neutralization (VN) assays were performed. Protection against H5N1 virus challenge was evaluated in ferrets. Results Intranasal immunization with rH5-NE01vaccine induced high titers (>106) of rH5-specific IgG in mice. In mice and ferrets this vaccine also achieved titers of ≥40 for both HI and VN. Additionally, the levels of rH5-specific IgA were significantly increased in bronchial secretions in these animals. The rH5-NE01 vaccine enhanced rH5-specific cellular immune responses including IFN-γ and IL-17. Ten-day survival post challenge was 100% in ferrets that received rH5-NE01compared to 12.5% in the PBS group. Furthermore, this vaccine prevented weight loss and increases in body temperature after H5N1 challenge as compared to the controls. Moreover, H5N1 virus in nasal wash of rH5-NE01-vaccinated ferrets was significantly decreased compared to controls. Conclusion Intranasal immunization with rH5 antigen formulated with NE01 adjuvant elicited strong, broad and balanced immune responses that effectively protect against H5N1 influenza virus infection in the ferret model. The ease of formulation of rH5-NE01 makes this novel combination a promising mucosal vaccine candidate for pandemic influenza.

Chronic inflammatory pain is a severe clinical symptom that aggravates the life quality of patients and places a huge economic burden on individuals and society. As one complementary and alternative therapy, electroacupuncture (EA) is widely used in clinical practice to treat chronic inflammatory pain based on its safety and efficacy. Previous studies have revealed the potential role of adenosine, neuropeptides, and inflammatory factors in EA analgesia in various pain models, but the identity of some of the signaling pathways involved remain unknown. In the present study, we explored whether neuregulin1 (NRG1)-ErbB4 signaling is involved in EA analgesia in inflammatory pain. Repeated EA treatment at the acupoints Zusanli (ST36) and Sanyinjiao (SP6) for 3 consecutive days remarkably attenuated mechanical allodynia and thermal hyperalgesia in complete Freund’s adjuvant (CFA)-treated mice, with an increased expression of NRG1 in spinal cord (SC). We found that ErbB4 kinase participated in both the EA and NRG1 mediated analgesic effects on inflammatory pain by pharmacological inhibition or genetic ablation ErbB4 in vivo. Intriguingly, the mice with conditional knockout of ErbB4 from PV+ interneurons in SC showed abnormal basal mechanical threshold. Meanwhile, NRG1 treatment could not relieve tactile allodynia in PV-Erbb4–/– mice or AAV-PV-Erbb4–/– mice after CFA injection. These experimental results suggest that regulating NRG1-ErbB4 signaling in SC could reduce pain hypersensitivity and contribute to EA analgesia in inflammatory pain.

Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development., Infections triggered by pathogenic fungi cause a serious threat to the public health care system. In particular, an increase of antifungal drug-resistant fungi has resulted in difficulty in treatment. A limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study, we demonstrate the efficacy of the nanoemulsion NB-201, which utilizes the surfactant benzalkonium chloride, against human-pathogenic fungi. We found that NB-201 exhibited in vitro activity against Candida albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented an enhanced healing process after subcutaneous infections by multidrug-resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp., Aspergillus fumigatus, and Mucorales. Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance developing, presenting a novel treatment to control fungal wound or skin infections. IMPORTANCE Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development.

Silicon photonic integrated devices used for nonlinear optical signal processing play a key role in ultrafast switching, computing, and modern optical communications. However, current devices suffer from limited operation speeds and low conversion efficiencies due to the intrinsically low nonlinear index of silicon. In this paper, we experimentally demonstrate enhanced optical nonlinearity in a silicon–organic hybrid slot waveguide consisting of an ultranarrow slot waveguide coated with a highly nonlinear organic material. The fabricated slot area is as narrow as 45 nm, which is, to the best of our knowledge, the narrowest slot width that has been experimentally reported in silicon slot waveguides. The nonlinear coefficient of the proposed device with a length of 3 mm is measured to be up to 1.43 × 10 6 W − 1 km − 1 . Based on the nanostructure design, the conversion efficiencies of degenerate four-wave mixing showed enhancements of more than 12 dB and 5 dB compared to those measured for an identical device without the organic material and a silicon strip waveguide, respectively. As a proof of concept, all-optical canonical logic units based on the prepared device with two inputs at 40 Gb/s are analyzed. The obtained logic results showed clear temporal waveforms and wide-open eye diagrams with error-free performance, illustrating that our device has great potential for use in high-speed all-optical signal processing and high-performance computing in the nodes and terminals of optical networks.

It is very significant to monitor livestock foraging behavior accurately and in real-time to further improve pasture management and livestock welfare. Although various algorithms have been developed to identify and classify animals' foraging behavior, it still has room to be improved in generality and function. In this study, a representative acoustic dataset generated by typical bodyweight sheep when grazing on various grasses and subsequent ruminating was created. Then an algorithm for the identification and classification of foraging behavior was proposed based on feature extraction technique and deep learning. Specifically, all prominent fragments in the acoustic signal were identified as events by the identification algorithm, and the events were classified as noise, chew, bite, chew-bite, or ruminating behavior through the classification model. The effect of each parameter on the identification algorithm was analyzed, and an optimal set of parameters was derived. As a result, the accuracy of 96.13% was achieved by the identification algorithm with the optimal parameters. Meanwhile, the performances of three common deep network models, including deep neural network (DNN), convolutional neural network (CNN), and recurrent neural network (RNN), were compared. The results showed that the RNN, CNN, and DNN model's accuracy were 93.17%, 92.53%, and 79.43%, respectively. The RNN model had a stronger classification capacity than the CNN model since it involved the inter-dependent information of adjacent events. The CNN model achieved a superior classification performance than the DNN model because the log-scaled Mel-spectrogram representation of the event waveform was more effective than the waveform itself. The algorithm proposed in this study could be well applied to identify and classify all foraging behaviors of typical weight sheep foraging freely on various grasses in the future.

Aim: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options. Materials & methods: NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA. Results: Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds and inhibited epidermal and deep dermal inflammation. The levels of proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds. Conclusion: NB-201 can greatly reduce inflammation characteristic of infected wounds and has antimicrobial activity that effectively kills MRSA regardless of the genetic basis of antibiotic resistance.

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients., Graphical Abstract

Background Vaccination is the most effective approach to prevent infection with highly pathogenic avian influenza (HPAI). Adjuvants are often used to induce effective immune responses and overcome the immunological weakness of recombinant HPAI antigens. Given the logistical challenges of immunization to HPAI during pandemic situations, vaccines administered via the intramuscular (I.M.) route would be of value. Methods A new formulation of nanoemulsion adjuvant (NE02) suitable for I.M. vaccination was developed. This NE02 was evaluated alone and in combination with CpG to develop H5 immune responses in mouse and ferret models. Measures of recombinant H5 (rH5) specific immunity evaluated included serum IgG and IgG subclasses, bronchoalveolar lavage fluid IgA, and cytokines. The activation of NF-kB was also analyzed. The efficacy of the vaccine was assessed by performing hemagglutination inhibition (HAI), virus neutralization (VN) assays, and viral challenges in ferrets. Results I.M. vaccination with rH5-NE02 significantly increased rH5-specific IgG and protected ferrets in the viral challenge model providing complete protection and sterile immunity in all animals tested. Combining NE02 and CpG produced accelerated antibody responses and this was accompanied by an elevation of IFN-γ and IL-17 responses and the downregulation of IL-5. The combination also caused a synergistic effect on NF-kB activation. In immunized ferrets after viral challenge, the rH5-NE02 + CpG vaccine via I.M. achieved at least 75% and 88% seroconversion of HAI and VN antibody responses, respectively, and improved body temperature stabilization and weight loss over NE02 alone. Conclusions The I.M. injection of NE02 adjuvanted rH5 elicits strong and broad immune responses against H5 antigens and effectively protects animals from lethal H5 challenge. Combining this adjuvant with CpG enhanced immune responses and provided improvements in outcomes to viral challenge in ferrets. The results suggest that combinations of adjuvants may be useful to enhance H5 immune responses and improve protection against influenza infection.

The emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. An increase antifungal drug resistant fungi have posed a serious threat to patients. Combining these circumstances with a limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study we present the utilization of the nanoemulsion NB-201 to control human pathogenic fungi. We found that the NB-201 exhibited in vitro activity against C. albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented enhanced healing process after subcutaneous infections by multidrug resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp, Aspergillus fumigatus, and Mucorales. Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance to develop, thus presents a novel treatment to control fungal wound or skin infections.

Polymer dots (Pdots) represent newly developed semiconductor polymer nanoparticles and exhibit excellent characteristics as fluorescent probes. To improve the sensitivity and biocompatibility of Pdots ratiometric pH biosensors, we synthesized 3 types of water-soluble Pdots: Pdots-PF, Pdots-PP, and Pdots-PPF by different combinations of fluorescent dyes poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO), poly[(9,9-dioctyl-fluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1&prime, 3}-thiadazole)] (PFBT), and fluorescein isothiocyanate (FITC). We found that Pdots-PPF exhibits optimal performance on pH sensing. PFO and FITC in Pdots-PPF produce pH-insensitive (&lambda, = 439 nm) and pH-sensitive (&lambda, = 517 nm) fluorescence respectively upon a single excitation at 380 nm wavelength, which enables Pdots-PPF ratiometric pH sensing ability. F&ouml, rster resonance energy transfer (FRET) together with the use of PFBT amplify the FITC signal, which enables Pdots-PPF robust sensitivity to pH. The emission intensity ratio (I517/I439) of Pdots-PPF changes linearly as a function of pH within the range of pH 3.0 to 8.0. Pdots-PPF also possesses desirable reversibility and stability in pH measurement. More importantly, Pdots-PPF was successfully used for cell imaging in Hela cells, exhibiting effective cellular uptake and low cytotoxicity. Our study suggests the promising potential of Pdots-PPF as an in vivo biomarker.

Pharmacophore is a commonly used method for molecular simulation, including ligand-based pharmacophore (LBP) and structure-based pharmacophore (SBP). LBP can be utilized to identify active compounds usual with lower accuracy, and SBP is able to use for distinguishing active compounds from inactive compounds with frequently higher missing rates. Merged pharmacophore (MP) is presented to integrate advantages and avoid shortcomings of LBP and SBP. In this work, LBP and SBP models were constructed for the study of peroxisome proliferator receptor-alpha (PPARα) agonists. According to the comparison of the two types of pharmacophore models, mainly and secondarily pharmacological features were identified. The weight and tolerance values of these pharmacological features were adjusted to construct MP models by single-factor explorations and orthogonal experimental design based on SBP model. Then, the reliability and screening efficiency of the best MP model were validated by three databases. The best MP model was utilized to compute PPARα activity of compounds from traditional Chinese medicine. The screening efficiency of MP model outperformed individual LBP or SBP model for PPARα agonists, and was similar to combinatorial screening of LBP and SBP. However, MP model might have an advantage over the combination of LBP and SBP in evaluating the activity of compounds and avoiding the inconsistent prediction of LBP and SBP, which would be beneficial to guide drug design and optimization.

Online social networks like twitter are self-organized systems with emergent behaviors from the individual interactions. Predicting the users’ behaviors like posting, replying or retweeting is one of the most important issue. In the paper, we present a method to model the twitter users’ posting behavior with the other users’ response. We also contrast the simulation precision with the model that does not involve the other users’ response. We make use of a stochastic model with Markov chain to predict a specific user’s next tweeting behavior. From the result by contrasting the simulation data and the real data, we demonstrate that the engineering method is able to predict individual posting behaviors based on time windows. In addition, the proposed model involving other users’ response is better than that only considering posting time sequences.

In order to meet the high precision and real-time demand of master-slave robot, the motion controller of it is designed with field programmable gate array (FPGA) as the core chip. The controller firstly implements real-time Ethernet Powerlink instead of the traditional field bus to transfer location information between master-slave hands, then PID closed-loop control algorithm calculates an pulse width modulation (PWM) duty cycle based on the deviation from the location information of master-slave hands, PWM generation module generates corresponding square wave signal to drive the motor rotates. To feedback actual location information and ensure the security of system, encoder acquisition module and motor enable module are designed with logical hardware in FPGA. Finally the motor position control is realized. The results of experiments show that the motion controller based on FPGA, which is compared with the traditional motion controller realized by digital signal processor (DSP) and FPGA, can greatly improve the precision and real-time performance of master-slave robot.

Rotavirus may be an important causative agent of acute gastroenteritis (AGE) in the elderly, a population that is particularly vulnerable due to waning immunity. It is estimated that rotavirus may account for 2-5% of adult gastroenteritis hospitalizations in the United States. This is the first study to assess the safety and immunogenicity of the live pentavalent rotavirus vaccine (RV5) in an elderly population. In this study, healthy, independently living adults aged 65-80 years were randomized in a 2:1 ratio to receive three 2-mL oral doses of RV5 or placebo administered 28-42 days apart. All subjects were followed for safety for 42 days post any vaccination and up to 180 days after the final vaccination for clinical adverse events. Immunogenicity of RV5 was measured by serum anti-rotavirus IgA enzyme immunoassay and serum neutralizing antibody responses to human rotavirus serotypes prior to and after each dose. Results of this study demonstrated that RV5 was generally safe and well tolerated in healthy elderly adults, where 9% of placebo and 27% of RV5 recipients experienced a vaccine-related adverse event of mild or moderate intensity. Immune responses (serum anti-rotavirus immunoglobulin A [IgA] and serum neutralizing antibodies against human rotavirus serotypes in the vaccine) were augmented in this population after a single dose of RV5, despite the factors of older age and preexisting antibodies to the virus. Therefore, if vaccination in the elderly is needed, further evaluation of RV5 as a candidate vaccine in this age group may be warranted.

The structural characteristics and requirements of a bucket, combined with the working experience of an excavator, were analyzed to optimize the structure of a WK-20 bucket. The simulation model was defined by the discrete element method (DEM) to characterize the real interaction between the bucket and different materials. Through an analysis and comparison of the performance of the original and optimized buckets, the latter increased the filling coefficient for different materials. The simulation and optimization based on DEM offered the theoretical basis and a reliable method for the reasonable design of the bucket structure and the entire machine.

Only when mining at reasonable cutting speed, can a mechanical excavator achieve high efficient and low consumption. The same cutting-angle logarithmic spiral trajectory is initially confirmed for the model of a reasonable excavating trajectory to reduce digging resistance. An analytical expression between hoisting and pushing speed is derived from the mechanism kinematics theory and the constraint equation method. This expression accurately describes the cooperative relationship between these speeds. Virtual prototype kinematics of a large mechanical excavator are simulated and verified through ADAMS. The simulation result is consistent with the theoretical result, and thus validates the analytical expression between hoisting and pushing speed.

Carrier aggregation technology is a key technology of LTE-Advanced,which is proposed by 3GPP organization as a 4G technology. This paper describes its application within 230MHz power industry existing authorized spectrum, aggregate the discrete narrowband, combine with some other technologies, such as OFDM, to build an innovative 230MHz power radio broadband communication system to achieve broadband transmission of power data. The laboratory theoretical simulation and pilot project verify that this application effectively take advantage of the power existing spectrum, can fully meet the bandwidth needs of power data transmission, presents a thought to solve the status of existing discrete authorized spectrum and its restriction on power radio data transmission.

The electric power system is a complex distributed system of large dimension, nonlinear, time-varying and uncertain dynamic parameters, the control and decision need expert experience, so the experts in electric power system as the control mechanism is relatively reasonable has been increasingly recognized. Automatic generation of state warning, exception reporting, monitoring of the equipment maintenance scheme and application of expert system. In this paper, by using the fault tree logic function description and fuzzy algorithm theory research of expert system based on expert system, so that the power has more accurate knowledge base and higher correctness of reasoning, in order to needs of production and operation of the power system to meet the better.

We investigate experimentally the dynamics of a liquid droplet that displaces on the micro-grooved surfaces driven by a controlled air flow. A range of experiments were carried out on the surfaces which patterned micro grooves with different directions and dimensions. The velocity required to initiate droplet motion increased with the grooves’ dimensions. Displacement was obtained easier on the parallel micro-grooved surfaces compare to the vertical micro-grooved surface. Then a force balance model was constructed based on the capillary force and driving force. The analytical results were well consistent with the experiments. We suggest that the force model could be exploited in a reasonable estimate for the initiation velocity on a micro-grooved surface.

To determine the safe distance between spreader and the upper verge of dump slope, a 2D and 3D slope model was built respectively, the limit equilibrium method and the finite element method with shear strength reduction technique (FEM-SSR) were introduced to analyze the stability of the spreader. For the slope under the action of variable external loads, the simple genetic algorithm (SGA) sometimes fails to converge to the global optimum, for this reason, an improved optimum maintaining simple genetic algorithm (OMSGA) was utilized to search for the critical slip surface, and the probability of the global convergence was improved greatly. On the basis of the three-dimensional elastic-plastic finite element model of the dump slope, the minimum sinkage of spreader track which interferes the spreaders normal operation was taken as the criterion to determine the safety factor, according to this idea, the deformation in the elastic stage during the process of strength reduction was considered, and a more reliable safety factor by the variable stiffness method was obtained.

Despite advances in antimicrobial therapies, wound infection remains a global public health concern. We aimed to formulate and assess various nanoemulsions (NEs) for potential effectiveness as stable antimicrobial agents suitable for topic application. A total of 106 NEs were developed that varied with respect to nonionic and cationic surfactants. Stability testing demonstrated that the NEs tested are broadly stable, with 97/106 formulations passing 2-week stability tests. Two NEs, NB-201 and NB-402, were selected to test antimicrobial activity in a wound model in mice. Skin abrasion wounds were infected with Staphylococcus aureus followed by NE treatment. Infected skin was then evaluated by measuring colony forming units. NB-201 reduced median bacterial counts by 4 to 5 log compared to animals treated with saline, whereas NB-402 reduced bacterial counts by 2 to 3 log. Additional stability tests on NB-201 demonstrated that NB-201 is stable in the presence of human serum, and is stable for at least 6 months at 5°C, 25°C, and 40°C. Finally, in in vitro studies, NB-201 was found to be effective against S. aureus at a higher dilution than the commercially available silver sulfadiazine. Altogether these results demonstrate that NB-201 is a stable and effective topical antimicrobial for the treatment of S. aureus.

Aim: The aim of this study was to investigate the impact of a novel nanoemulsion (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in mice as a study model. Materials & methods: Mice received NE or NE + mTg by nasal delivery. At 1 week after the second nasal delivery of NE with or without mTg, all mice were immunized with mTg and lipopolysaccharides to induce experimental autoimmune thyroiditis. Results: Compared with controls, mTg–NE-treated mice had much more antigens accumulated in the nasal passage and thymus and developed a milder form of thyroiditis. This was accompanied by an increase in IL-10, IL-17 and reduced IFN-γ. The production of anti-mTg antibodies was significantly decreased in mTg–NE-treated mice. The percentage of Tregs in cervical lymph nodes was higher in mTg–NE-treated mice than NE-treated mice. Furthermore, Foxp3 and TGF-β levels were prominently enhanced in mTg–NE-treated mice. Conclusion: This study indicates that a low dose of mTg in NE can significantly enhance antigen uptake and Tregs, resulting in inhibition of experimental autoimmune thyroiditis development. Original submitted 17 September 2011; Revised submitted 5 December 2011; Published online 15 March 2012

Background: The pentavalent rotavirus vaccine (PRV), RotaTeq, can be concomitantly administered with most routine childhood vaccines. This study evaluated the immunogenicity and reactogenicity of PRV when used concomitantly with a hexavalent vaccine containing diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b. Methods: Healthy infants (N = 403) received hexavalent vaccine concomitantly with either PRV or placebo at 2, 3, and 4 months of age. Antibody responses were measured immediately before and 42 +/- 3 days after vaccination. Parents/legal guardians recorded all adverse events for 14 days after vaccination. Results: Seroprotective titers for hepatitis B (hepatitis B surface antigen >=10 mIU/mL) were achieved by 97.8% of subjects in both vaccine treatment groups. Seroprotective titers to H. influenzae type b (polyribosylribitol phosphate >=0.15 [mu]g/mL) were achieved by 91.4% of subjects receiving both vaccines and 95.1% of subjects receiving only hexavalent vaccine. Seroprotective titers to diphtheria, tetanus, and poliovirus were also comparable between the vaccine treatment groups, as were geometric mean antibody titers to the pertussis antigens. Among PRV recipients, 92% had a >=3-fold rise in serum antirotavirus immunoglobulin A levels. Concomitant administration was well tolerated. The incidence of adverse events was similar for both groups, with no statistically significant increases in fever, vomiting, diarrhea, or irritability. Conclusions: In this study, concomitant administration of PRV with hexavalent vaccine was well tolerated and the immune responses to the antigens of the hexavalent vaccine were noninferior when compared with those of the control group. In addition, PRV was immunogenic when administered concomitantly with hexavalent vaccine.

There have been several reports that TNF-related apoptosis-inducing ligand (TRAIL) has the ability to suppress the development of experimental autoimmune diseases, including a mouse model of experimental autoimmune encephalomyelitis, a rabbit model of rheumatoid arthritis, type 1 diabetes mellitus, in mice and experimental autoimmune thyroiditis (EAT) in mice. However, the mechanism underlying TRAIL effect is not well defined. In the present study, we specifically examined TRAIL effects on CD4(+)CD25(+) regulatory T cells. CD4(+)CD25(+) T cells prepared from mouse thyroglobulin (mTg)-immunized CBA/J mice proliferate in the presence of TRAIL and dendritic cells in vitro. These CD4(+)CD25(+) T cells included both CD4(+)CD25(+)CD45RB(Low) (regulatory) and CD4(+)CD25(+)CD45RB(High) (effector) T cells. Our results demonstrated that mTg-immunized mice treated with TRAIL showed significant increases in the number of CD4(+)CD25(+)CD45RB(Low) T cells compared with mice immunized with mTg alone. CD4(+)CD25(+)CD45RB(Low) T cells expressed much higher levels of the forkhead family transcription factor, IL-10, and TGFbeta1 than CD4(+)CD25(+)CD45RB(High) T cells, and these cells can completely suppress the proliferation of the mTg-primed splenocytes in lower concentrations than the unfractionated CD4(+)CD25(+) T cells. Furthermore, transfer of these cells into CBA/J mice prior to mTg-primed splenocyte injection could markedly reduce the frequency and severity of EAT development. CD4(+)CD25(+)CD45RB(Low) T cells were more effective at suppressing histological thyroiditis than unfractionated cells. These results indicated that TRAIL can increase the number of mTg-specific CD4(+)CD25(+)CD45RB(Low) T cells, inhibiting autoimmune responses and preventing the progression of EAT. These findings reveal a novel mechanism by which TRAIL could inhibit autoimmune disease.

93 compounds which can permeate the placenta barrier were collected as data set for the construction of support vector regression (SVR) model. Besides, 140 compounds with reproductive toxicity and 170 compounds with no reproductive toxicity were collected as another data set for the construction of support vector classification (SVC) model. 1481 molecular descriptors were calculated to represent the structure characteristics of all the compounds mentioned above by Dragon2.1. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to optimize the subset of molecular descriptors. Then based on the above data, SVR model for prediction the placenta barrier permeability (PBP) and SVC model for prediction the reproductive toxicity were built respectively by using LibSVM program. Both the SVR model and the SVC model obtained better prediction ability. The correlation coefficient (R) values of the training set and test set of the optimal SVR model were 0.990 and 0.780. The accuracy, sensitivity, and specificity values of the optimal SVC model were all above 80%. Subsequently, the SVR model was utilized to predict the PBP of the compounds which were collected from 13 commonly used tocolytic Chinese herbs. The compounds with higher permeability were further studied by the SVC model and 15 compounds were classified as positive compounds with reproductive toxicity. The two models constructed in this study might be employed in guiding the application of the tocolytic Chinese herbs in clinical. Introduction Traditional Chinese medicine (TCM) has been regarded as the main medical for the treatment of diseases throughout East Asia with a history of 5000 years. It has been widely used to promote health and treat illnesses since then and accepted as a major approach of complementary and alternative medicine in Western world in recent years. According to the theory of TCM [1], miscarriage is defined as “fetal irritability”, “fetal restlessness” or “stirring fetus”, and TCM has unique herbs to reduce the risk of miscarriage. However, the information about the application of tocolytic Chinese herbs for miscarriage is limited [2] [3]. Besides, tocolytic Chinese herbs may lead toxic effects to the fetus by transferring across the placenta barrier. Therefore it is urgent to investigate whether the active compounds with high placenta barrier permeability (PBP) are reproductive toxicity or not, for the safety of tocolytic Chinese herbs application. Support vector machine (SVM), of which the contents involved the aspects of the maximum-margin hyperplane, Mercer’s kernels and so on, serves as a new artificial intelligence technology [4]. In practice, it consists of two modes: SVC and SVR. The former is a qualitative method, which is focus on the pattern recognition and classification; the latter is a quantitative method for prediction and forecasting [4]. Meanwhile, the time-consuming and high-cost problem caused by traditional toxicological experiments can be alleviated by SVM [5]. In this paper, a drug molecule-based SVR model was built for evaluating the PBP of tocolytic Chinese herbs compounds which derived from the Traditional Chinese Medicine Database (TCMD, version 2009). Then on this basis, a drug molecule-based SVC model was constructed to predict the reproductive toxicity of the active compounds with relatively high PBP. Thus, the SVR and SVC models of tocolytic International Conference on Materials Engineering and Information Technology Applications (MEITA 2015) © 2015. The authors Published by Atlantis Press 650 compounds were constructed to discover the compounds with reproductive toxicity from Chinese herbs, which may provide guidance for the safety application of tocolytic Chinese herbs in clinical. Materials and methods Training and test sets splitting. The PBP of compounds is typically expressed in relative permeability (RP). Antipyrine, a small lipophilic compound that is known to be transported across the placenta via passive diffusion [6], was used as a reference compound to make the data gathered in multiple laboratories comparable. Then, for the generation of SVR model, 93 compounds that have been reported to have PBP were collected as SVR data set from references [7-12]. To ensure the training set were well representative, the “Kennard-Stone (KS)” program [13] was used to randomly split the SVR data set into a training set containing 73 compounds and a test set with 20 compounds (namely SVR-TS1). On the other hand, for the generation of SVC model, a data set including140 reproductive toxicity compounds (positive) and 170 non-reproductive toxicity compounds (negative) were collected from references [14-17]. The data set was also split by KS. 125 positives and 125 negatives were chosen as training set, and 15 positives and 45 negatives were regarded as internal test set (namely SVC-TS1). Then, to further evaluate the SVC models, we constructed another two independent external test sets, namely SVC-TS2 and SVC-TS3. To be specific, SVC-TS2 was comprised of 455 negatives, which were derived from the “approved” drug molecules in DrugBank (http://www.drugbank.ca/); SVC-TS3 was comprised of 5 Chinese herbs that had been reported to bear reproductive toxicity [18-22]. There is no overlap between each set mentioned above, and the results of splitting training and test sets are detailed in Table 1. Table 1. The data structure partitioning results for each model. The PBP SVR model The reproductive toxicity SVC model Training set SVR-TS1 Training set+ Training setSVC-TS1+ SVC-TS1SVC-TS2SVC-TS3+ 73 20 125 125 15 45 455 5 (+) positive compounds. (-) negative compounds. Molecular descriptors. Dragon2.1 was used for descriptors calculation for all compounds in all data sets and 1481 molecular descriptors were computed. For feature selection, BestFirst-D1-N5, CfsSubsetEval and 10-fold cross-validation were performed in Weka3.6.10 [23]. Three data normalization methods, including no-normalization, [0, 1] and [-1, 1], were performed for each object. Then, those three data processing results for each study object were used for further study, respectively. Development of SVM. SVM is an important machine learning method and is rigorously used in both bioinformatics and chemoinformatics. In this study, LibSVM-Faruto-Ultimate (Version2.0), developed by Faruto, was used to run the SVM algorithm, including SVC and SVR. Appropriate kernel function and parameters are crucial and should be chosen while using SVM to settle factual classification problem. In order to map input vectors into a higher dimensional space nonlinearly, RBF Kernel was chosen as the kernel function of both SVC and SVR. Besides, C and γ are two parameters in RBF kernel, which greatly affect the precision of SVM classifier. In order to ensure the classifier could predict test set accurately, three parameter optimization methods, called Grid Search, Genetic Algorithm (GA) and Particle Swarm Optimization (PSO), were used to identify appropriate (C, γ). In addition, the default parameters were also retained for model construction. Thus, 4 parameter selection methods were used to build SVM models based on 3 data processing results. Data analysis and model validation. Firstly, SVR-TS1 was applied to validate the SVR models so that the relationship between structural variables and placenta barrier RP could be

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice. One week later, the recipient mice were treated with recombinant TRAIL or a control protein. Compared with control animals, TRAIL-treated mice developed a milder form of the disease with a significant decrease in mononuclear cell infiltration in the thyroid and less thyroid follicular destruction. Furthermore, the number of apoptotic thyrocytes and also thyroglobulin-specific T helper-1 cell responses in TRAIL-treated mice was lower than that in the control animals. This study suggests that exogenous TRAIL suppresses the development of autoimmune thyroiditis via altering the function of cells involved in the immune response. These findings may contribute toward a novel treatment autoimmune thyroiditis.

Treatment of cultured primary human thyroid cells with IFN-γ and TNF-α uniquely allows the induction of Fas-mediated apoptosis. To investigate the role of this cytokine combination in vivo, CBA/J mice were immunized with thyroglobulin and then injected with IFN-γ and TNF-α. Compared with control animals, mice treated with IFN-γ and TNF-α showed significantly sustained lymphocytic infiltration in the thyroid, which was associated with the destruction of portions of the follicular architecture at wk 6 after initial immunization. Furthermore, the number of apoptotic thyroid follicular cells was increased only in the thyroids from mice treated with the IFN-γ and TNF-α. We also analyzed the function of the Fas pathway in vivo in cytokine-treated mice by using an agonist anti-Fas Ab injected directly into the thyroid. Minimal apoptosis of thyroid epithelial cells was observed unless the mice were pretreated with IFN-γ and TNF-α. These data demonstrate that this unique combination of inflammatory cytokines facilitates the apoptotic destruction of thyroid follicular cells in experimental autoimmune thyroiditis, in a manner similar to what is observed in Hashimoto’s thyroiditis in humans.

In this paper, we propose models to characterize the process of opinion spreading in signed social networks under the impact of structure balance. We classify users into different types according to their positive link numbers, and define the term user influence to characterize the average number of times that users are influenced, which is incurred by a user spreading an opinion. We then present an approach to analyze the user influence theoretically, and the accuracy is verified by simulations.

Kangaroo care is no longer performed for the initial purpose of maintaining a small baby's body temperature in the developed countries where there are now sufficient medical equipments to keep babies warm. The objectives of kangaroo care in advanced neonatal ICUs have changed to provide benefits such as bonding and attachment, physiologic stability of newborn babies, successful breastfeeding and positive effects on infant development. Kangaroo care is not new to many neonatal nurses, but not every neonatal center is routinely practicing kangaroo care in Singapore. Inadequate nurses' knowledge and lack of guidelines on kangaroo care hinder its practice.The aim of this project was to implement kangaroo care in very low birth weight babies in a systematic and structured approach.The team followed Larrabee's The Model For Evidence-Based Practice Change, used the available evidence on kangaroo care to develop guideline that was specific and suitable for the local setting. The team organized kangaroo care road shows for nurses and parents to create and enhance awareness. Evaluation of the project was done through two audits. The audit tool consisted of correct baby positioning and nursing documentation, with a sample size of 30 episodes.The ages of the babies audited were from 24 to 34 weeks of gestation with their weight ranging from 850 to 1500 g. The compliance rate for correct baby positioning during kangaroo care was 100% for both audits. The compliance rate for nursing documentation improved from 93% in the first post-implementation audit to 96.7% in the second post-implementation audit.The systematic and structured approach in kangaroo care implementation has created awareness among nurses and led to improvements in their knowledge and practices of kangaroo care. The implementation process of kangaroo care has also aided in training the ward Evidence-Based Nursing Unit team members to engage in critical thinking, which ultimately benefited the babies and parents.

Resistance spot welding has been widely used for joining sheet metals, especially in automotive and aerospace industries. However, since the formation of weld nugget is invisible in resistance spot welding, traditionally off-line destructive test is applied for inspection of the weld quality, which is costly and inefficient. Therefore, in recent years, a lot of efforts have been made in estimating or detecting the weld quality nondestructively by on-line welding parameter monitoring. This paper presents a review on techniques of monitoring resistance spot welding process or weld quality, and the advantages as well as limitations of these techniques are discussed.

Twitter trends, a timely updated set of top terms in Twitter, have the ability to affect the public agenda of the community and have attracted much attention. Unfortunately, in the wrong hands, Twitter trends can also be abused to mislead people. In this paper, we attempt to investigate whether Twitter trends are secure from the manipulation of malicious users. We collect more than 69 million tweets from 5 million accounts. Using the collected tweets, we first conduct a data analysis and discover evidence of Twitter trend manipulation. Then, we study at the topic level and infer the key factors that can determine whether a topic starts trending due to its popularity, coverage, transmission, potential coverage, or reputation. What we find is that except for transmission, all of factors above are closely related to trending. Finally, we further investigate the trending manipulation from the perspective of compromised and fake accounts and discuss countermeasures.

As P2P-TV applications are widely used on the Internet, its disadvantages shows up with its conventions, particular the easier spread of erotic, violent or pirated content. To address this problem, this paper presents a system that can accurately identify and closely monitor the P2P-TV traffic passing through a campus network. It consists of five core modules: data collection, traffic identification, active measurement, video content detection and filter, and center of visualization. The basic flow of the content monitoring contains five steps: 1) the data collection module collects mixed traffic from the campus gateway, 2) the traffic identification module classifies the mirrored traffic and identifies the P2P-TV traffic flows of the corresponding platforms and their channels watching by the viewers in the campus network, 3) the active measurement module is driven to probe the behavior, IP addresses and geographical positions of online viewers, 4) the video content detection and filter module recovers the video content from the identified P2P-TV traffic and performs anomaly detection, and 5) the center of visualization module is responsible to interact with other modules and visualizes all results on the web in various manners.

Thyroiditis consists of a number of different inflammatory processes in thyroid and is caused by a variety of factors. Among the various inflammatory thyroid lesions, Hashimoto’s thyroiditis is the most common, and we will focus on the mechanisms involved in this disease. While extensive studies have been performed to elucidate the immunopathogenesis of Hashimoto’s thyroiditis, the processes underlying this disease are still not fully understood. However, significant progress has been made in areas related to the roles that iodine, CD4+CD25+ regulatory T cells, and apoptosis play in autoimmune-mediated thyroid damage, the defining feature of Hashimoto’s thyroiditis.

Apoptosis has been demonstrated as an important process in both thyroid carcinogenesis and therapy. Alterations in an increasing number of apoptotic molecules have been associated with thyroid cancer. Advances in understanding apoptosis have provided not only the new concept of how the tumor develops but also novel strategies in management of this malignancy. This chapter summarizes recent publications on apoptosis in thyroid cancer. Three main aspects of this topic are discussed: apoptotic pathways in cancer, how apoptosis is linked to the development of thyroid cancer, and the possible therapeutic implications of the molecular regulation of apoptosis.

Primary thyroid cells are resistant to TNF-related apoptosis-inducing ligand (TRAIL). Previously we showed that the combination of IL-1beta and TNFalpha facilitated TRAIL-mediated apoptosis in these cells and enhanced cell surface expression of TRAIL receptors. The aim of this study was to further characterize the mechanism by which these cytokines sensitized primary thyroid cells to TRAIL-mediated apoptosis. IL-1beta and TNFalpha increased the concentrations of procaspase-7 and Bid. In contrast, the p44/42 MAPK (Erk) pathway was active in thyroid cells and this activity was significantly decreased after exposure to IL-1beta/TNFalpha. A MAPK kinase inhibitor (U0126) could enhance the cytokine-induced sensitization of thyroid cells to TRAIL, reinforcing the inhibitory role of Erk on TRAIL signaling. In conclusion, IL-1beta/TNFalpha treatment sensitizes human thyroid cells to TRAIL-mediated apoptosis through increased surface expression of TRAIL receptors, increased expression of procaspase-7 and Bid, and the inhibition of p44/42 MAPK (Erk) pathway.

We have investigated experimentally the process of a droplet impact on a regular micro-grooved surface. The target surfaces are patterned such that micro-scale spokes radiate from the center, concentric circles, and parallel lines on the polishing copper plate, using Quasi-LIGA molding technology. The dynamic behavior of water droplets impacting on these structured surfaces is examined using a high-speed camera, including the drop impact processes, the maximum spreading diameters, and the lengths and numbers of fingers at different values of Weber number. Experimental results validate that the spreading processes are arrested on all target surfaces at low velocity. Also, the experimental results at higher impact velocity demonstrate that the spreading process is conducted on the surface parallel to the micro-grooves, but is arrested in the direction perpendicular to the micro-grooves. Besides, the lengths of fingers increase observably, even when they are ejected out as tiny droplets along the groove direction, at the same time the drop recoil velocity is reduced by micro-grooves which are parallel to the spreading direction, but not by micro-grooves which are vertical to the spreading direction.

According to the characteristics of coherent structures in near-wall turbulence, an accurate extraction and verification method is developed based on wavelet transform (WT) and correlation analysis in this paper. At first, the fluid field of a turbulent boundary layer is measured precisely in a gravitational low-speed water tunnel. On the basis of the distribution of the coherent structures, velocity data of three test points are selected and analyzed, whose dimensionless heights are 20.8, 33.5, and 42.6. According to the frequency range of power spectrum density (PSD), coherent and incoherent structures are both extracted from the original signals using continuous and orthogonal wavelet transforms. To confirm the validity of the extracted signals, the probability density function (PDF) of each extracted signal is calculated. The result demonstrates that the incoherent structures obey the Gaussian distribution, while the coherent structures deviate from the Gaussian distribution. The PDFs of the coherent structures and the original signals are similar, which shows that the coherent structures make most contributions to the turbulence. For further verification, a correlation parameter between coherent and incoherent structures is defined, which evidently proves the validity of the extraction method in this paper.

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice.