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It is generally believed that the lift–drag ratio is closely related to the hydrodynamic performance and sailing efficiency of the underwater glider. The underwater glider carries limited energy, making it particularly important to increase the sailing efficiency through selection of an appropriate lift–drag ratio. Considering this, the energy consumption per meter is introduced as the indicator of sailing efficiency and the energy consumption models under given net buoyancy and glide speed are established, respectively. Then, the optimal lift–drag ratio for sailing efficiency is obtained through these two models. The result shows that under given net buoyancy, the sailing efficiency has positive correlation with the lift–drag ratio. The optimal lift–drag ratio at this time is the maximum lift–drag ratio that can be obtained at a speed above the minimum allowable, and the glider shapes with a high ultimate lift–drag ratio, such as the flying wing layout or high aspect ratio wings, can be adopted. However, under a given speed, it is not the higher the better for the lift–drag ratio, but the optimal lift–drag ratio is a constant value only related to the shape of the glider to maximize the sailing efficiency. What's more, the glider shapes with a low ultimate lift–drag ratio, such as low aspect ratio wings, can decrease the lower limit of minimum energy consumption per meter and also can be adopted under a given speed.

Type 2 diabetes mellitus (DM) is a highly prevalent chronic metabolic disease. Effective antidiabetic drugs are needed to improve and expand the available treatments. Using the ob/ob diabetic mouse model, we previously demonstrated that the alkaloid-rich extract from Litsea glutinosa bark (CG) has potent antidiabetic effects and that laurolitsine (LL) is the richest alkaloid in CG.We conducted a systematic investigation of the antidiabetic effects and potential mechanisms of LL in vitro and in vivo.The antidiabetic effects of LL and its mechanisms of action were explored in HL-7702 hepatocytes in vitro and in db/db mice in vivo by a series of experiments, including cellular toxicity analysis, glucose consumption analysis, serum/liver biochemical analysis, pathological examinations, Western blots, RNA-seq analysis, and gut microbiota analysis.LL stimulated glucose consumption and activated AMP-activated protein kinase (AMPK) without inducing lactic acid production or cytotoxicity in vitro. LL had potent antidiabetic effects with hypoglycemic activity in vivo. It improved insulin resistance, glucose tolerance and lipid metabolism; protected liver, renal and pancreatic functions; and promoted weight loss in db/db mice. Transcriptomic analysis suggested that the antidiabetic effects of LL involved the regulation of mitochondrial oxidative phosphorylation. We further demonstrated that LL effectively activated the hepatic liver kinase B1 (LKB1)/AMPK pathway by regulating the ADP/ATP ratio. Simultaneously, LL significantly modulated the gut microbial community, specifically decreasing the abundances of Mucispirillum schaedleri and Anaerotruncus_sp_G3_2012, which might also contribute to its antidiabetic effects.These results suggest that LL is a promising antidiabetic drug candidate that may improve glucolipid metabolism via modulation of the hepatic LKB1/AMPK pathway and the gut microbiota.

Downstream fining of riverbed gravels is generally linked with the processes of hydraulic sorting and abrasion. Hydraulic sorting is when larger gravel clasts stop moving in response to decreasing flow energy, whereas, finer grains will continue to be carried downstream. Furthermore, transportation of gravel clasts causes abrasion, bringing about a gradual decrease in grain size. Hydraulic sorting and abrasion have different dominant effects on the downstream fining of clasts in rivers with different climatic and tectonic backgrounds. At present, most studies focus on humid areas, and relatively few studies have explored this issue for the northeastern margin of the Tibetan Plateau in arid and semi-arid areas. Detailed investigations of the grain size, lithology, and roundness of riverbed gravels have been performed here along the Taolai, Hongshuiba, and Fengle Rivers, which flow across the northeastern margin of the Tibetan Plateau and debouch into the arid inland of North China. The obtained data were subsequently employed in a hydraulic pattern of grain-size distribution of riverbed gravels in this area, which is characterized by the combined influences of tectonic activity and climatic aridity. Analysis reveals that there is no new rock type appearing in the lithological compositions of riverbed gravels along these rivers, only showing fluctuations in proportions of lithology even though they are adjacent to uplifting mountains. Fresh gravel material from these mountains does indeed mix into the fluvial bedload, inducing a notable decrease in roundness in the Taolai and Hongshuiba bedloads downstream from here. The downstream fining of gravel along the three rivers, with median grain sizes above 128 mm and falling into the range from 20 to 128 mm, can probably be attributed to hydraulic sorting and abrasion. Further analysis suggests that the former presents a high correlation with channel gradient, which may be sustained by fault activity at the northeastern margin of the Tibetan Plateau. The grain-size distribution in these riverbed gravels thus provides insights into the evaluation of fluvial responses to active tectonic uplift.

Understanding the signaling pathway regulatory mechanisms in type II alveolar epithelial (ATII) cells, the progenitor cells responsible for proliferating and regenerating type I alveolar epithelial (ATI) and ATII cells, in Tibetan pigs is beneficial for exploring methods of preventing and repairing cellular damage during hypoxia. We simulated a hypoxic environment (2% O2) for culture ATII cells of Tibetan pigs and Landrace pigs, with cells cultured under normoxic conditions (21% O2) as a control group, and performed integrated analysis of circular RNA (circRNA)–microRNA (miRNA)–messenger RNA (mRNA) regulatory axes by whole-transcriptome sequencing. Functional enrichment analysis indicated that the source genes of the differential expressed circRNAs (DEcircRNAs) were primarily involved in cell proliferation, cellular processes, and cell killing. A series of DEcircRNAs were derived from inhibitors of apoptosis proteins and led to a key autonomous effect as modulators of cell repair in Tibetan pigs under hypoxia. The significant higher expression of COL5A1 in TL groups may inhibited apoptosis of ATII cells in Tibetan pigs under lower oxygen concentration, and may lead their better survive in the hypoxia environment. In addition, a competing endogenous RNA (ceRNA) network of functional interactions was constructed that included novel_circ_000898-ssc-miR-199a-5p-CAV1 and novel_circ_000898-ssc-miR-378-BMP2, based on the node genes ssc-miR-199a-5p and ssc-miR-378, which may regulate multiple miRNAs and mRNAs that mediate endoplasmic reticulum (ER) stress-induced apoptosis and inflammation and attenuate hypoxia-induced injury in ATII cells under hypoxic conditions. These results broaden our knowledge of circRNAs, miRNAs, and mRNAs associated with hypoxia and provide new insights into the hypoxic response of ATII cells in Tibetan pigs.

This paper analyzes the sensitivity of the artificial viscosity in the defect deferred correction method for the non-stationary coupled Stokes/Darcy model. For the defect step and the deferred correction step of the defect deferred correction method, we respectively give the corresponding sensitivity systems related to the change of artificial viscosity. Finite element schemes are devised for computing solutions to the sensitivity systems. Finally, we will verify the theoretical analysis results through numerical experiments. Our results reveal that the solution is sensitive for small values of the artificial viscosity, and when the viscosity/hydraulic conductivity coefficients are small.

Self-activated Ca5 Mg3 Zn(VO4 )6 and Ca5 Mg3 Zn(VO4 )6 :xEu3+ phosphors were synthesized via a high-temperature solid-state reaction route. The crystalline structure and luminescence properties of the phosphors were analyzed using an X-ray diffractometer and a photoluminescence spectrometer. The explored results indicated that by varying calcination temperature and the raw material ratio of Ca2+ /Mg2+ /Zn2+ , the phosphors could be developed with different phases, crystallinity, and various fluorescence performances. The fluorescence spectrum of Ca5 Mg3 Zn(VO4 )6 showed a broad emission band over the range 400-650 nm under an excitation wavelength of 330 nm, as well as green light emission. Furthermore, after introduction of Eu3+ ions in Eu(VO4 )4 , the luminescence intensity of the Eu3+ ions greatly increased as the Eu3+ ion concentration increased at the 393 nm excitation wavelength, showing green-yellow light emission simultaneously. Therefore, the obtained phosphors could be used as a potential green-yellow-emitting luminescent material in a white light-emitting diode device.

In this study, porous composite materials were prepared from calcium citrate (CC) and polylactic acid (PLA). Scanning electron microscopy (SEM) showed that the prepared composite materials had the ...

Aims To conduct molecular tagging of the biocontrol fungus Trichoderma asperellum strain T4 and elucidate its colonization patterns in soil. Methods and results We constructed an expression vector harbouring a hygromycin B-resistant gene (hph) and an efficient green fluorescent protein (egfp) gene. By applying Agrobacterium AGL-1-mediated genetic transformation technology, we conducted molecular tagging of T. asperellum and monitored the colonization dynamics of T. asperellum in soil. The results of tracking five independent transformants of T. asperellum indicated that its expansion rates ranged from 4·7 to 6·8 cm week-1 . After inoculation in soil, the quantities of T. asperellum could be maintained at over 10 × 104 CFU per gram soil in the first year. In the third year after inoculation, the quantities of T. asperellum in soil were still higher than 1 × 103 CFU per gram soil. In addition, molecularly tagged T. asperellum in soil in the second year (i.e. 12 months) after inoculation could still reach the biocontrol effect on cucumber Rhizoctonia rot by more than 74%. Conclusion Trichoderma asperellum strain T4 is capable of effectively colonizing in soil and surviving for more than 1 year. Significance and impact of the study This study has provided the scientific basis for applying T. asperellum as the biocontrol fungus for prevention and control of plant diseases.

Terraces achieve water storage and sediment function by slowing down the slope and soil erosion. This kind of terraced or wave-section farmland built along the contour line is a high-yield and stable farmland facility with key construction in the dry farming area. It provides a strong guarantee for increasing grain production and farmers' income. In recent years, Gansu province has carried out a large amount of construction on terraces, however, due to the poor quality of the previous construction and management, the terraced facilities were in danger of being destroyed. In order to prevent and repair the terraces, it is necessary to timely and accurately extract the terrace information. The segmentation of terraces can be obtained by edge extraction, but the effect of satellite data is not ideal. With the continuous development of remote sensing technology of drones, the acquisition of high-precision terrace topographic information has become possible. In this research, the slope was extracted from the digital elevation model data in the data preprocessing stage, and the orthophoto data of the three experimental areas were merged with the corresponding slope data, respectively. Then the rough edge extraction method based on Canny operator and the fine edge extraction method based on multi-scale segmentation were used to perform edge detection on two data sources. Finally, the influence of slope on the extraction of terraced edges of remote sensing images of UAVs was analyzed based on the overall accuracy of edge detection and user accuracy. The experimental results showed that, in the rough edge extraction method, the data source accuracy of the fusion slope and image was improved by 23.97% in the OA precision evaluation, and the average improvement in the user's accuracy was 20.68%. In the fine edge extraction method, the accuracy based on the data source 2 was also increased by 17.84% on average in the overall accuracy evaluation of the data source 1, and by an average of 19.0% in the UV accuracy evaluation. The research shows that in the extraction of terraced edges of UAV remote sensing images, adding certain terrain features can achieve better edge extraction results.

To explore the metabolic effect of chemerin, adipose-specific chemerin knockout (adipo-chemerin-/- ) male mice were established and fed with 5-week normal diet (ND) or high-fat diet (HFD), and then the glycolipid metabolism index was measured and epididymal adipose tissue metabolomics detected using untargeted LC-tandem mass spectrometry (LC-MS/MS). Under HFD, adipo-chemerin-/- mice showed improved glycolipid metabolism (decreased total cholesterol, low-density lipoprotein-cholesterol, insulin and Homeostasis Model Assessment of Insulin Resistance) compared with flox (control) mice. Furthermore, orthogonal partial least squares-discriminant analysis score plots identified separation of metabolites between adipo-chemerin-/- mice and flox mice fed ND and HFD. Under HFD, 28 metabolites were significantly enhanced in adipo-chemerin-/- mice, and pathway enrichment analysis suggested strong relationship of the differential metabolites with arginine and proline metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis, which were directly or indirectly related to lipid metabolism, inflammation and oxidative stress. Under ND, taurine was increased in adipo-chemerin-/- mice, resulting in taurine and hypotaurine metabolism and primary bile acid biosynthesis. In conclusion, the improved effect of chemerin knockdown on the glycolipid metabolism of HFD-feeding male mice might be associated with the increases in differential metabolites and metabolic pathways involved in lipid metabolism, inflammation and oxidative stress, which provided insights into the mechanism of chemerin from a metabolomics aspect.

Underwater thermal vehicles, as ocean observation tools, are frequently affected by environment disturbances such as waves and currents, which may cause degradation of the observation accuracy of the vehicles. Consequently, it is important to design a controller for a vehicle that can resist ocean disturbance. In this study, an underwater thermal vehicle principle is introduced, and the mathematical model is established in the vertical plane motion. On this basis, an adaptive digital disturbance suppression control method is proposed. For known disturbance parameters, this controller could compensate for external disturbances by pre-setting control parameters using the internal model principle and parameterizations method. For the case where the disturbance parameters are unknown, disturbance parameter estimation method based on forgetting factor least-squares method is proposed to transform the unknown parameter disturbance into a disturbance with known parameters, which is then suppressed by the adaptive digital disturbance rejection control approach. This solution could effectively solve the challenges caused by parameter uncertainty and unknown time-varying ocean external disturbances. Finally, simulations are carried out for the Petrel underwater thermal glider as an example. The simulation results show the proposed control method’s superiority and inherent robustness.

Underwater vehicle is one of the most important tools for ocean observation and exploration. The application of ocean thermal energy conversion can greatly extend its duration and range. The challenge in developing the system resides in the proper sizing and integration of the components to enhance the efficiency of energy conversion. This study proposes the ocean thermal energy conversion for underwater vehicles. It utilizes phase change material to collect ocean thermal energy from warm near-surface and converts it into the potential energy stored in a hydraulic accumulator, which is transformed into electrical energy for the power supply by using hydraulic motor, generator and other components. Based on its working principle, the heat to electricity power generation system efficiency model is established, and validated by comparing measurements and predictions for a laboratory system. Factors influencing the efficiency of power generation are thoroughly analyzed. Moreover, primary design guidelines based on commercially available components are deduced from the proposed model. A prototype is developed and a sea trial is conducted to validate performance of the prototype. The results show that the energy harvested by the prototype can reach 6696 J per dive cycle with 6 kg phase-change material. The maximum hydraulic-to-kinetic efficiency of about 70% and maximum kinetic-to-electric efficiency of about 80% were achieved in the system. The maximum and average energy conversion efficiency are respectively 0.55% and 0.396%. Therefore, high efficiency and good performance of prototype were validated which implied a possibility to improve the range and navigation time of underwater vehicles.

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

Extant research argues most EMNEs prefer lower-level integrations to manage up-market resources. Yet antecedents have not been fully identified; how and why EMNEs change integrations over time remains unclear. This dissertation tackled the questions of EMNEs' PMI modes and influencing factors in up-markets, with one publication found five organizational cultural dimensions that affect EMNEs’ integration levels, and another developed EMNEs' static integration framework to be a dynamic framework and identified main influencing factors at various integration stages. Dass EMNEs eine Präferenz für geringe Integration der im entwickelten Markt akquirierten Ressourcen besitzen. Dabei wurden Faktoren identifiziert nicht völlig, welche die EMNE-Integration beeinflussen. Unerklärt bleibt auch, wie und warum EMNEs ihre Integrationsstrategien anpassen. Diese Dissertation identifiziert dabei fünf Primärdimensionen der Organisationskultur, welche die EMNE-Integration in entwickelten Märkten behandeln beeinflussen und entwickelt eine dynamischen und mehrstufigen Integrationskonzept und identifiziert Faktoren in den verschiedenen Integrationsphasen beeinflussen.

Underwater vehicles are one of the most important tools for ocean observation and exploration, whose duration and range of underwater vehicles can be significantly extended by harvesting and utilizing ocean thermal energy. Generally, most underwater vehicles use the thermal engine to harvest ocean thermal energy. The phase change material (PCM)is the most important component of the thermal engine, the heat transfer performance of which directly affects the performance of the underwater vehicle. Enhancing the thermal conductivity of phase change materials is an effective way to improve the heat transfer rate of underwater thermal vehicles. The heat transfer performance of thermal engine can be effectively improved by incorporating graphene into PCM. In this paper, the molecular dynamic simulations of PCM with different addition ratio of graphene were carried out. Then the models of temperature-pressure-density, temperature-pressure-thermal conductivity and pressure-heat capacity were established for different simulation systems. On this basis, the internal connection between the additive ratio of graphene and the heat transfer rate of the thermal engine was revealed by using the phase change heat transfer model considering pressure conditions. The simulation shows that the appropriate addition of graphene is beneficial to the heat transfer rate of thermal engine at 0.1 MPa. Under the pressure condition of 20 MPa, the thermal engine can achieve the highest the heat transfer rate when the addition ratio is 1.2%, which also shows the best performance under simulated ocean conditions. The melting time can be reduced by 11.97% compared with the thermal engine without added graphene.

Supplemental Digital Content is available in the text, Background: At present, the effect of western-medicine (WM) therapy to treat diabetic peripheral neuropathy (DPN) is limited. Moxibustion is a representative external treatment in traditional Chinese medicine that has been beneficial to DPN. We aim to systematically assess the efficacy and safety of moxibustion in treating DPN, following PRISMA guidelines. Methods: Eight electronic databases were searched to acquire information on eligible trials published from inception to June 1, 2019. We included randomized controlled trials (RCTs) applying moxibustion therapy with a minimum of 14-days treatment duration for DPN patients compared with placebo, no intervention, or conventional WM interventions. The primary outcomes in our study include the sensory-nerve conduction velocity (SNCV) and motor-nerve conduction velocity (MNCV). We used the Cochrane Collaboration Risk of Bias tool to assess the methodological quality of eligible RCTs. Statistical analyses were conducted using Review Manager 5.3. Risk ratios (RR) and mean differences (MD) were calculated with a 95% confidence interval (CI). The χ2 test was applied to assess the heterogeneity. Results: In total, 11 RCTs were included that involved 927 DPN patients. Compared with the control group, there was an increase in median MNCV (MD = 6.26, 95% CI 2.64–9.89, Z = 3.39, P = .0007) and peroneal MNCV (MD = 6.45, 95% CI 5.30–7.61, P

Aiming at the problem of fast certification for a constrained iris in the same category caused by the unstable iris features caused by the change of the iris acquisition environment and shooting status under lightweight training samples, a one-to-one fast certification algorithm for constrained unsteady-state iris based on the scale change stable feature and multi-algorithm voting is proposed. Scale change stable features are found by constructing an isometric differential Gaussian space, and a local binary pattern algorithm with extended statistics (ES-LBP), the Haar wavelet with over threshold detection and the Gabor filter algorithm with immune particle swarm optimization (IPSO) are used to represent the stable features as binary feature codes. Iris certification is performed by the Hamming distance. According to the certification results of three algorithms, the final result is obtained by multi-algorithm voting. Experiments with the JLU and CASIA iris libraries under the iris prerequisite conditions show that the correct recognition rate of this algorithm can reach a high level of 98% or more, indicating that this algorithm can improve the operation speed, accuracy and robustness of certification.

[ES] El trabajo se realiza dentro del contexto actual que se está viviendo dentro de la crisis mundial a causa del Covid-19. A raíz de este acontecimiento muchos son los aspectos de la vida diaria que han sufrido cambios o han tenido que reinventarse. En nuestro caso vamos a analizar el tema de la enseñanza online ya que es un debate que es de reciente actualidad. Con este trabajo de investigación en el que implementaremos la metodología cualitativa y cuantitativa queremos ver el papel de la enseñanza online y la efectividad que tiene dentro de la enseñanza de lenguas durante la epidemia que se ha vivido.

In [1], there was an error in the third line of equation (20). The correct equation (20) is as follows: \begin{equation*} \left\{ \begin{array}{l} {x_1} = \sqrt { - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} + \frac{{2 \times {2^{2/3}}}}{{9Z}} + \frac{{128 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} + \frac{{40 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} + \frac{1}{9} \times {2^{1/3}}Z} \\ {x_2} = - \sqrt { - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} + \frac{{2 \times {2^{2/3}}}}{{9Z}} + \frac{{128 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} + \frac{{40 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} + \frac{1}{9} \times {2^{1/3}}Z} \\ {x_3} = \sqrt{\begin{array}{l} - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} - \frac{{{2^{2/3}}}}{{9Z}} + \frac{{{2^{2/3}}}}{{3\sqrt 3 Z}}{\rm{i}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} + \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{3\sqrt 3 {K_L}^4Z}}{\rm{i}} \\ -\frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} + \frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{3\sqrt 3 {K_L}^2Z}}{\rm{i}} - \frac{Z}{{9 \times {2^{2/3}}}} - \frac{Z}{{3 \times {2^{2/3}}\sqrt 3}}{\rm{i}} \end{array}}\\ {x_4} = - \sqrt {\begin{array}{l} - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} - \frac{{{2^{2/3}}}}{{9Z}} + \frac{{{2^{2/3}}}}{{3\sqrt 3 Z}}{\rm{i}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} + \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{3\sqrt 3 {K_L}^4Z}}{\rm{i}} \\ -\frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} + \frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{3\sqrt 3 {K_L}^2Z}}{\rm{i}} - \frac{Z}{{9 \times {2^{2/3}}}} - \frac{Z}{{3 \times {2^{2/3}}\sqrt 3}}{\rm{i}} \end{array}} \\ {x_5} = \sqrt {\begin{array}{l} - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} - \frac{{{2^{2/3}}}}{{9Z}} - \frac{{{2^{2/3}}}}{{3\sqrt 3 Z}}{\rm{i}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{3\sqrt 3 {K_L}^4Z}}{\rm{i}} - \\ \frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} - \frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{3\sqrt 3 {K_L}^2Z}}{\rm{i}} - \frac{Z}{{9 \times {2^{2/3}}}} + \frac{Z}{{3 \times {2^{2/3}}\sqrt 3}}{\rm{i}} \end{array}} \\ {x_6} = - \sqrt {\begin{array}{l} - \frac{2}{9} + \frac{{16{K_D}{K_{D0}}}}{{9{K_L}^2}} - \frac{{{2^{2/3}}}}{{9Z}} - \frac{{{2^{2/3}}}}{{3\sqrt 3 Z}}{\rm{i}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{9{K_L}^4Z}} - \frac{{64 \times {2^{2/3}}{K_D}^2{K_{D0}}^2}}{{3\sqrt 3 {K_L}^4Z}}{\rm{i}} \\ -\frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{9{K_L}^2Z}} - \frac{{20 \times {2^{2/3}}{K_D}{K_{D0}}}}{{3\sqrt 3 {K_L}^2Z}}{\rm{i}} - \frac{Z}{{9 \times {2^{2/3}}}} + \frac{Z}{{3 \times {2^{2/3}}\sqrt 3}}{\rm{i}} \end{array}} \\ {x_7} = {\rm{i}}\\ {x_8} = - {\rm{i}} \end{array} \right. \end{equation*}

The passive buoyancy compensation liquid (PBCL) has been widely used in underwater vehicles operating in deep-sea environments to reduce buoyancy loss caused by hull deformation and seawater density variation. The heat transfer process of PBCL is an important factor that affects the net buoyancy and motion performance of the deep-sea glider (DG), which was commonly neglected. A comprehensive dynamic-thermal model for Petrel-4000 deep-sea glider (PDG) with PBCL is established in this paper. A model which considers the heat transfer process is proposed to estimate the volume change of PBCL. These models are verified by comparing the numerical results with experimental data. The effect of the heat transfer process on the motion performance of PDG is fully analyzed by comparisons with those not considering heat transfer process. Then, the effect of PBCL distribution is discussed, which shows that the reasonable PBCL distribution can facilitate a more stable gliding attitude of PDG. Energy consumption analysis is carried out and the results indicate that the application of PBCL is beneficial for energy saving, especially under the lower power of the control system and measurement system. The results and conclusions would provide a valuable reference for the design and engineering applications of DG.

Underwater glider is becoming an increasingly important tool for exploring the ocean. As the underwater tasks become more challenging, it puts forward higher requirements for the endurance of electric underwater gliders. This paper proposes an operation principle for the underwater glider jointly driven by the ocean thermal energy and the electrical energy, which has the advantages of both electric underwater glider and thermal underwater glider. Based on the proposed operation principle, a universal energy consumption model and sailing range equation suitable for the electric, thermal and hybrid propulsion underwater gliders are established. Taking the sailing range, sailing range difference and sailing range ratio as the evaluation indexes, the effects of configuration parameters and navigation parameters on the endurance of three underwater gliders are analyzed. The results show that the endurance and endurance advantage of hybrid propulsion underwater glider can be improved with greater volume change rate of phase change material (PCM), heavier energy carrier and smaller average power of the task sensor, and its high performance can also be maintained with a weight ratio of PCM close to the critical value. Meanwhile, it is beneficial to obtaining stronger endurance for the hybrid propulsion glider during its operation by setting larger diving depth as well as smaller gliding angle and volume change of oil within the design range. Finally, the hybrid propulsion prototype and Petrel-II electric underwater glider are deployed to carry out the comparative sea trial, which verifies the correctness of sailing range equation and the availability of prototype. The results show that the hybrid propulsion underwater glider has a better energy consumption economy than the electric underwater glider.

Methanotrophs can oxidize methane as the sole carbon and energy, and the resulting intermediate products can be simultaneously utilized by coexistent denitrifying bacteria to remove the nitrogen, which named Aerobic Methane Oxidation Coupled to Denitrification (AME-D). In this paper, an AME-D system was built in an improved denitrification bio-filter, to analyze the nitrogen removal efficiency and mechanism. The maximum TN removal rate reached 95.05%. As shown in Raman spectroscopy, in the effluent wave crests generated by the symmetric expansion and contraction of NO3- disappeared, and the distortion of olefin CH2 and C-OH stretching of alcohols appeared. Metagenomics revealed Methylotenera and Methylobacter were the dominated methanotrophs. There was a completed methane and nitrogen metabolism pathway with the synergism of nxrAB, narGHI, nasAB, pmo-amoABC and mmo genes. Dissimilatory reduction pathway was the primary nitrate removal pathway. Moreover, Bradyrhizobium could participate in methane and nitrogen metabolism simultaneously.

Underwater glider can achieve marine data through profile motion, which has become an important means of ocean observation. This paper proposes a positive buoyancy underwater glider, which retains the wings and internal moving mass of traditional glider, but has no variable buoyancy system. The glider maintains positive buoyancy during the profile motion and the diving process is realized by a thruster. The positive buoyancy glider can achieve a higher sailing efficiency when the zero angle of attack of the vehicle is achieved by setting a certain installation angle of the wings. In addition, since the positive buoyancy glider has no complicated variable buoyancy system and the oil-pumping process, and achieves profile motion by directly changing the attitude, it is more suitable for shallow-water survey and provides reference for the development of large-scale gliders. In this paper, energy consumption per meter is used as an indicator of sailing efficiency. The effects of glide angle, installation angle and net buoyancy on sailing efficiency are studied and the optimal installation angle is calculated. It is theoretically proved that the energy consumption per meter is equal in four glide modes of the positive buoyancy glider. When the glide angle of the traditional glider is steeper than the energy-consumption-equivalent glide angle, the positive buoyancy glider has a higher sailing efficiency, whose energy consumption per meter is irrelevant to the glide angle.

Background Maltotetraohydrolase, widely used in food and medical fields, possesses the ability to hydrolyze starch to produce maltooligosaccharides with maltotetraose as the main product. It also has the potential usage in delaying bread aging. Results Pseudomonas saccharophila maltotetraohydrolase was expressed in Bacillus subtilis WS11. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed obvious bands at 57 kDa (maltotetraohydrolase I) and 47 kDa (maltotetraohydrolase II). Both showed similar enzymatic properties, although the catalytic efficiency of maltotetraohydrolase I was 4.93 fold higher than that of maltotetraohydrolase II using soluble starch as substrate. In addition, the maltotetraohydrolase production was further scaled up in a 3-L fermentor, and the highest activity reached 1907 U mL-1 . Then, the recombinant maltotetraohydrolase was used to produce maltotetraose. The maltotetraose yields catalyzed by maltotetraohydrolase I and II reached 73.2% and 69.7%, respectively. Finally, when recombinant maltotetraohydrolase was used in bread-making, texture profile analysis of the bread indicated recombinant maltotetraohydrolase I exhibited a significant anti-aging effect. Conclusion This is the first describing high-efficient expression of P. saccharophila maltotetraohydrolase in the food safety strain B. subtilis, and the yield represented the highest level ever reported. Excellent results were also obtained with respect to the preparation of maltotetraose and delaying bread aging using the recombinant maltotetraohydrolase. The present study will help lay the foundation for the industrial production and application of maltotetraohydrolase. © 2020 Society of Chemical Industry.

早大学位記番号:新8503

Supplemental Digital Content is available in the text, Background: Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes mellitus (T2DM). Acupuncture has been increasingly used for prediabetes in China but its effect is unclear. We aim to assess the efficacy and safety of acupuncture in preventing or delaying incident diabetes among individuals with prediabetes. Methods: The following 8 databases will be searched from inception to September 1, 2018: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure database, Chinese Biomedical Literature database, Chinese Scientific Journal database, Wan Fang database, and Clinical Trials. The incidence of diabetes and regression toward normoglycemia will be accepted as the primary outcomes. The Cochrane Risk of Bias tool will be used to evaluate the methodologic quality of eligible studies. Meta-analysis will be performed by Review Manager 5.3. Results: This study will provide a high-quality synthesis of current evidence of acupuncture in the prevention of T2DM from several aspects including the incidence of diabetes, regression toward normoglycemia, fasting plasma glucose, 2-hour plasma glucose level after a 75-g oral glucose tolerance test, glycosylated hemoglobin level, body mass index, and adverse drug events. Conclusions: The conclusion of this review will provide evidence to judge whether acupuncture is an effective and safe intervention for prediabetes. PROSPERO registration number: PROSPERO CRD42018111236.

The Zn2+ doped Carbon Quantum Dots (Zn-CQDs) were synthesized with zinc citrate chelate as the precursor by a hydrothermal method. The evaluation results indicated that Zn2+ was successfully embedded in CQDs. Most of Zn2+ ions were combined with carboxyl groups on the surface of carbon dots to form Zn-O bonds and some Zn2+ ions were embedded in the interstice points of CQDs. The remaining Zn2+ were reduced to zinc atoms and adsorbed on the surface of CQDs. With the increase in Zn2+ concentration, the size of synthesized Zn-CQDs increased. When zinc ion concentration increased to 9%, the average size of Zn-CQDs grew up to 8 nm, but the size of undoped CQDs was just 1.5 nm. When Zn2+ concentration increased from 1% to 9%, the fluorescence intensity increased, while reaching above 9%, the fluorescence intensity showed a downward trend. When Zn2+ concentration was 7%, the fluorescence quantum yield of Zn-CQDs increased to 48%, but the fluorescence quantum yield of undoped CQDs was only 37%. With the increase in Zn2+ concentration, the PL spectrum of Zn-CQDs showed a red shift phenomenon. In addition, Zn-CQDs showed superior fluorescent sensing capability to Fe3+ and Hg2+, presenting greater fluorescence quenching effect on Fe3+ and Hg2+ than CA-CQDs. Therefore, Zn-CQDs demonstrated excellent fluorescence properties and can be applied in fluorescent sensor, biological imaging, optoelectronics, and catalysis fields.

Faced with the difficulty in finding and locating leakage points of submarine pipelines timely as well as the high cost of pipeline routine inspection, a scheme using autonomous underwater vehicle (AUV) equipped with multibeam echo sounder (MBES) and forward looking sonar (FLS) for automatic inspection of submarine pipelines was developed. In the process of inspection, the AUV maintains autonomous navigation along the pre-set pipeline route at a fixed height above the pipeline, while the MBES collects water column images. After extracting the outline characteristics of gas-filled bubbles and making a leakage risk judgment, it rises to the sea surface to issue an alarm to the shore-based command center via satellite. The results of sea trial verify the effectiveness of sub-sea pipeline leak detection and real-time obstacle avoidance of the vehicle proposed in this study. Additionally, a variable buoyancy system (VBS) is adopted, which enhances the navigation efficiency of the vehicle. On the other hand, considering the complex operation environment of the pipeline inspection, the online collision avoidance is indispensable. The traditional image segmentation algorithm is not ideal for the high noise and bottom reverberation in operation sea area. Based on the traditional algorithm, an improved Otsu algorithm is proposed to improve the operation speed and denoise effect. As a result, an improved Otsu algorithm is proposed to accurately identify obstacles. Moreover, Kalman filtering is also introduced to estimate dynamic obstacles.

Ocean thermal energy offers the possibility to solve the contradiction between long-term and high-frequency observation and finite power of unmanned underwater vehicles. There are very limited reviews on unmanned underwater vehicles powered by ocean thermal energy. This review is primarily dedicated to a comprehensive overview of ocean thermal unmanned underwater vehicle development, and an indication of future developments. Firstly, this paper provides a review of the current state of ocean thermal energy utilization in vehicles. The application principles of phase change material thermal harvesting system are concluded, and several typical PCM-based unmanned underwater vehicles are listed. Then, several theoretical issues based on this type of vehicle have been discussed. Moreover, the basic principles of ocean thermal energy utilization approaches based on shape memory alloys, thermoelectric generators, thermodynamic cycle, and their potential application forms in vehicles are also reviewed. Finally, the challenges and difficulties involved in the application of ocean thermal energy in unmanned underwater vehicles are discussed as well. The results show that (i): PCM-based vehicles are still the most promising ocean thermal underwater vehicles; (ii): For this type of vehicles, there are still some problems to be solved, such as slow heat transfer rate, low energy conversion efficiency (less than 0.6%), low energy storage density (about 0.26 Wh/kg) and lack of synergy between motion and heat transfer; (iii) The other three types of ocean thermal UUVs are still in the conceptual design phase, and their basic application principles, as well as the exploration of methods to improve energy density and efficiency, are the most critical focuses at present.

Underwater glider is one of the most popular platforms for long term ocean observation. Underwater glider driven by ocean thermal energy extends the duration and range of underwater glider powered by battery. Thermal engine is the core device of underwater glider to harvest ocean thermal energy. In this paper, (1) model of thermal engine was raised by thermodynamics method and the performance of thermal engine was investigated, (2) thermal engine with a double-tube structure was developed and isostatic pressing technology was applied to improve the performance for buoyancy driven, referencing powder pressing theory, (3) wall thickness of thermal engine was optimized to reduce the overall weight of thermal engine, (4) material selection and dimension determination were discussed for a faster heat transfer design, by thermal resistance analysis, (5) laboratory test and long term sea trail were carried out to test the performance of thermal engine. The study shows that volumetric change rate is the most important indicator to evaluating buoyancy-driven performance of a thermal engine, isostatic pressing technology is effective to improve volumetric change rate, actual volumetric change rate can reach 89.2% of the theoretical value and the average power is about 124 W in a typical diving profile. Thermal engine developed by Tianjin University is a superior thermal energy conversion device for underwater glider. Additionally, application of thermal engine provides a new solution for miniaturization of ocean thermal energy conversion.

The traditional neutral buoyancy underwater vehicle's carrying capacity is limited by space and displacement, making it difficult to meet the increasing demand for mission sensors. In light of this, a new type of negative-buoyancy autonomous underwater vehicle equipped with an autorotating rotor is proposed in this paper. Referring to the principle of air autorotating rotor, the negative-buoyancy autorotating-rotor autonomous underwater vehicle (NAAUV) adopts an autorotating rotor to provide lift and compensate for negative buoyancy, thus achieving effective navigation. Negative-buoyancy vehicles have greater carrying capacity, less use of buoyancy materials, smaller size of the vehicle, and lower resistance and energy consumption. To verify the working principle of NAAUV, a dynamic model is established and the navigation process of the vehicle is simulated. The results verify satisfactory navigation stability of the vehicle. Focus on the issue of the flapping and shimmy caused by inconsistent speeds of advancing and retreating rotor blades, the two-way fluid-structure interaction simulation method is adopted. As a result, flapping deformation and equivalent stress of the rotor are acquired. Because rotor material performance requirements are not strict, common metal materials can meet the requirements.

In this paper, a facile double-emulsion approach was reported to fabricate the silver nanoparticles (AgNPs)-doped hydroxyapatite/alginate nanocomposite microparticles. First, hydroxyapatite nanoparticles (HApNPs) were prepared using coprecipitation method, then, HApNPs were involved in sodium alginate (Alg) network to form HAp/Alg microparticles via emulsion process. Next, silver nitrate was involved into HAp/Alg microparticles using second emulsion, which ascorbic acid was used as a trigger to form in situ-AgNPs-doped HAp/Alg microparticles. Physicochemical properties of the nanocomposite microparticles were characterized by Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FT-IR) spectra, Dynamic Light Scattering (DLS), Ultraviolet-Visible (UV–vis) Absorption Spectra, and Thermogravimetric analysis (TG). It was demonstrated that AgNPs and HApNPs were evenly distributed in entire microparticles (diameter ∼550 nm). Furthermore, the AgNPs-doped HAp/Alg microparticles showed a good cytocompatibility by culturing with A549 cells. Finally, the microparticles displayed an excellent antibacterial activity against Gram-negative E. coli and Gram-positive S. aureus. Above results manifested the significance of the final microparticles in diverse biomedical applications.

Indoor air quality (IAQ) is associated with human health due to people spending most of their time indoors. Secondary organic aerosol (SOA) formation is an important source of fine airborne particles, which can cause acute airway effects and decreased lung function. SOA is a product of reactive organic gas (ROG) ozonolysis, which can be parameterized by the aerosol mass fraction (AMF). The AMF is the ratio of SOA formation mass to the reacted ROG mass, and it is positively correlated with the total organic aerosol mass concentration. α-Terpineol is a terpenoid that can have a strong emission rate indoors owing to consumer product usage. It reacts strongly with oxidants such as ozone, hydroxyl radical (OH), and nitrate radical (NO3), where those radicals are produced indoors due to ozone reaction with alkenes or nitrogen dioxide (NO2), respectively. Due to the fast reaction rates of α-terpineol with these oxidants, SOA formation has the potential to increase in-door fine particle concentrations. However, SOA formation from α-terpineol has not been systematically quantified. Therefore, the purpose of this work was to quantify SOA formation owing to α-terpineol ozonolysis, for two sets of experiments, one without and one with NO2 present. In the first set of 21 experiments, the SOA formation initiated by reacting 6.39 to 226 ppb α-terpineol with high ozone (~25 ppm) to ensure rapid and complete ozonolysis for high (0.84 h−1), moderate (0.61 h−1) and low (0.36 h−1) air exchange rates (AER) was studied in a stainless steel chamber system. The resulting SOA mass formation was parameterized with the AMF for all experiments. The impact of reacted α-terpineol and AERs on AMFs as well as the SOA size distribution was investigated, and different AMF models (one-product, two-product, and volatility basis set) were fit to the AMF data. Predictive modeling investigated the impact of the SOA formation from α-terpineol ozonolysis in residential indoor air. Furthermore, a second set of 21 experiments in a Teflon bag operated as semi-batch reactor explored the impact of NO2 at 0 to 2000 ppb on SOA formation from α-terpineol ranging from 20 ppb to 200 ppb with excess ozone (~25ppm). In this system, ozone can either initiate reactions with α-terpineol to produce organic peroxy radicals (RO2∙) or react with NO2 to produce NO3, which can react with α-terpineol. For analysis of results, we classified experiments by logarithmic spacing into four groups according to the initial ratio of VOC/NO2 values. SOA mass was again parameterized by the AMF as a function of the organic aerosol concentration. The impact of VOC/NO2 on SOA mass as well as the SOA size distribution was investigated, and the SOA composition for each grouping of experiments was elucidated by the kinetic modeling. Finally, this SOA formation was put into context using the 'secondary intake fraction' (siF), which is a developed metric that evaluates SOA exposure during various human activities. The siF is defined as the up-taken mass of a secondary product for an exposed individual per unit mass of primary product emitted during human residential activities, over a given exposure time. The siF for individual intake was evaluated for SOA formation from d-limonene, α-terpineol, or α-pinene ozonolysis in five residential scenarios, including: I. Constant emission, II. Pulse emission, III. Surface cleaning, IV. Solution cleaning, and V. Skin cleaning. For a given input set, a transient model was used to predict SOA concentrations and the siF, using inputs cast as probability distributions within a Monte Carlo approach. Multiple linear regression techniques were applied to fit siF values for the five scenarios, for use in sensitivity analyses. Also, the multiple linear regression results can be used to predict the siF and the potential for human intake of SOA within exposure models.

Since the lighting conditions in strong contrast regions between the light and dark cant be estimated accurately by traditional center/surround Retinex algorithm, the over-enhancement and color distortion may exist. In view of this, combining with the human visual characteristics, a color image enhancement algorithm based on tone-preserving was proposed. A determination function was added to the bilateral filter to estimate illuminance image more accurately and weaken over-enhancement. According to human visual masking effect, the improved gamma correction was utilized to correct the brightness of illumination image adaptively and the local contrast of reflection image obtained by division was enhanced based on local statistics. Besides, the final enhanced image was obtained by combining illumination image with reflection image, which can make image appear more natural. Compared with other similar algorithms from both subjective and objective aspects, the results show that this method being applied to low-contrast color image enhancement can not only improve image clarity, but reduce color distortion.

A novel insulin analog, PIns, with N-terminal Arg-4, Pro-3, Lys-2, Pro-1extension at human regular insulin B-chain was acquired through gene engineering. Preproinsulin for PIns was cloned and expressed using a bacterial expression system at a high level (72.1%) as fusion protein carrying a modified thioredoxin N-terminal region (1-21) linked to N-terminus of proinsulin by a lysine residue. Purified fusion protein was refolded and converted into PIns by a single enzymatic reaction. After PIns was purified, the homogeneity of it was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis, isoelectronic focusing electrophoresis, amino acid composition analysis and mass spectrometry methods. A decreased tendency of self-association of PIns as compared with regular insulin was demonstrated by the size exclusion HPLC analysis. When subcutaneously administrated into normal rats, the PIns showed a faster rate of onset of action and a shorter duration of action compared with regular insulin, similar to the pharmacokinetic characteristics of insulin Lispro. These results showed that PIns is a rapid insulin analog. Furthermore, the N-terminal Arg-4, Pro-3, Lys-2, Pro-1extension at insulin B-chain can be excised by DPPIV and recombinant peptidase with DPPIV-like activities. It is suggested that PIns serves as an artificial insulin precursor and can be transformed to regular insulin in vivo due to the truncation of N-terminal sequence of PIns B-chain by DPPIV.

MicroRNA-200 (miR-200) has emerged as a regulator of the PI3K/AKT pathway and cancer cell growth. It was reported that miR-200 can activate PI3K/AKT by targeting FOG2 (friend of GATA 2), which directly binds to the p85α regulatory subunit of PI3K. We found that miR-200 was elevated in early stage lung adenocarcinomas when compared with normal lung tissues, and the expression of miR-200 promoted the tumor spheroid growth of lung adenocarcinoma cells. We show that AKT activation was essential for such oncogenic action of miR-200. However, depletion of FOG2 had little effect on AKT activation. By performing a reverse-phase protein array, we found that miR-200 not only activated AKT but also concomitantly inactivated S6K and increased IRS-1, an S6K substrate that is increased on S6K inactivation. Depletion of IRS-1 partially inhibited the miR-200-dependent AKT activation. Taken together, our results suggest that miR-200 may activate AKT in lung adenocarcinoma cells through a FOG2-independent mechanism involving IRS-1. Our findings also provide evidence that increased miR-200 expression may contribute to early lung tumorigenesis and that AKT inhibitors may be useful for the treatment of miR-200-dependent tumor cell growth.

Lung cancer is one of the most common types of human malignancies and the leading cause of cancer-related death. Patients with surgically resectable early stage lung cancer are more likely curable, but currently only a small population of patients can be diagnosed at such a stage, partly due to our incomplete understanding of the biology of lung cancer and the lack of diagnostic and prognostic biomarkers. Recent studies have shown that NOTCH1 is a critical regulator of human carcinogenesis and has been implicated in multiple steps of cancer development and progression. Herein, we review recent findings about the role of NOTCH1 in lung cancer and discuss its potential usefulness as both a therapeutic target and a biomarker for lung cancer.

Thermal glider is a new type of underwater glider which harvests its propulsive energy from the thermocline in the ocean. Compared with traditional electric underwater glider, the thermal glider may achieve a much longer duration and range. The heat exchangers on the underwater glider can be mounted above the hull, below the hull, and by the sides of the hull. In this paper, hydrodynamic analysis is conducted for the thermal glider with the three heat exchanger layout designs using computational fluid dynamics. Impact of the layout design on glide efficiency and static stability is investigated, using lift to drag ratio and dimensionless position lever as the evaluation parameters. Result shows that the thermal glider is statically stable with the heat exchangers. The layout of the heat exchangers greatly affects the static stability of the glider, while little influence has been found on the glide efficiency. It is also found that taking glide efficiency and static stability into consideration, the heat exchangers are better mounted below the hull. The result provides theoretical guidance for thermal glider design.

The thermal-powered glider is a small, autonomous underwater vehicle which absorbs the energy of the ocean thermocline to propel the glider. The thermal engine is the key part of this glider, which affects the range and speed of the glider. The engine is composed of middle bellows, an accumulator, an external bladder, front bellows, and an electrical pump. In this paper, component layout of the thermal engine is analyzed and optimized. Result shows that the optimal position of the external bladder is at the tail while the optimal of the front bellows is at the nose. The optimal layout of the external bladder and the front bellows causes a 24% decrease in moving distance of the mechanical moving object. It is also found that the optimal positions of the accumulator and the middle bellows are close to the buoyant center. The overall moving distance of the mechanical moving object is reduced 43% by the optimal arrangement. Besides, a new thermal engine is developed by adding a gear pump to make the glider get across the areas short of temperature difference energy.

Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine or paracrine growth factor that can stimulate the growth of various cancer cells, making it an ideal target antigen to develop vaccines against cancer. In this study, we developed a novel DNA vaccine that encodes six tandem repeats of B-cell epitope GRP(18-27) (GRP6) flanked by HSP65 as carrier and four tandem repeats of mycobacterial HSP70(407-426) (M4) as helper T-cell epitopes for enhancement of immunogenicity. When intramuscularly immunized to mice, this anti-GRP DNA vaccine-induced GRP-specific antibody (Ab) responses that were at least 10-fold higher in magnitude compared with HSP65-GRP6 protein vaccine. Both prophylactic and therapeutic antitumor immunities induced by vaccination significantly suppressed the growth of GRP-dependent prostate carcinoma RM-1 in vivo and prolonged the survival of tumor-inoculated mice. Out results also showed that the immune sera with high titer of GRP-specific Abs effectively inhibited the growth of tumor in mice and dose dependently inhibited proliferation of cultured RM-1 cells in vitro, suggesting that the GRP neutralizing Ab is responsible for the protective and therapeutic antitumor activity of vaccination. These findings may be of great importance in the further exploration of the applications of growth factors identified in human in cancer therapy.

Pharmacologic blockade of EGFR or the closely related receptor ERBB2 has modest efficacy against colorectal cancers in the clinic. Although the upregulation of ERBB3, a pseudo-kinase member of the EGFR/ERBB family, is known to contribute to EGFR inhibitor resistance in other cancers, its functions in normal and malignant intestinal epithelium have not been defined. We have shown here that the intestinal epithelium of mice with intestine-specific genetic ablation of Erbb3 exhibits no cytological abnormalities but does exhibit loss of expression of ERBB4 and sensitivity to intestinal damage. By contrast, intestine-specific Erbb3 ablation resulted in almost complete absence of intestinal tumors in the ApcMin mouse model of colon cancer. Unlike nontransformed epithelium lacking ERBB3, intestinal tumors lacking ERBB3 had reduced PI3K/AKT signaling, which led to attenuation of tumorigenesis via a tumor-specific increase in caspase-3–mediated apoptosis. Consistent with the mouse data, which suggest that ERBB3-ERBB4 heterodimers contribute to colon cancer survival, experimentally induced loss of ERBB3 in a KRAS mutant human colon cancer cell line was associated with loss of ERBB4 expression, and siRNA knockdown of either ERBB3 or ERBB4 resulted in elevated levels of apoptosis. These results indicate that the ERBB3 pseudo-kinase has essential roles in supporting intestinal tumorigenesis and suggest that ERBB3 may be a promising target for the treatment of colorectal cancers.

Epithelial tumor cells transit to a mesenchymal state in response to extracellular cues, in a process known as epithelial-to-mesenchymal transition (EMT). The precise nature of these cues has not been fully defined, an important issue given that EMT is an early event in tumor metastasis. Here, we have found that a population of metastasis-prone mouse lung adenocarcinoma cells expresses Notch and Notch ligands and that the Notch ligand Jagged2 promotes metastasis. Mechanistically, Jagged2 was found to promote metastasis by increasing the expression of GATA-binding (Gata) factors, which suppressed expression of the microRNA-200 (miR-200) family of microRNAs that target the transcriptional repressors that drive EMT and thereby induced EMT. Reciprocally, miR-200 inhibited expression of Gata3, which reversed EMT and abrogated metastasis, suggesting that Gata3 and miR-200 are mutually inhibitory and have opposing effects on EMT and metastasis. Consistent with this, high levels of Gata3 expression correlated with EMT in primary tumors from 2 cohorts of lung adenocarcinoma patients. These findings reveal what we believe to be a novel Jagged2/miR-200-dependent pathway that mediates lung adenocarcinoma EMT and metastasis in mice and may have implications for the treatment of human epithelial tumors. Refereed/Peer-reviewed