Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and ach...Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms.Due to the limited range of the a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.展开更多
Background: Inhibition of the lymphoma surface antigen CD40 by the antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various lymphoma subtypes. In this preclinical in vivo study we examined the s...Background: Inhibition of the lymphoma surface antigen CD40 by the antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various lymphoma subtypes. In this preclinical in vivo study we examined the suitability of positron emission tomography (PET) using the thymidine analogue 3’-deoxy-3’-[18F]fluorothymidine (FLT) for early response assessment upon HCD122 treatment in diffuse large B cell lymphoma (DLBCL). Methods: Immunodeficient mice bearing human DLBCL xenografts (SU-DHL-4) received weekly intraperitoneal injections of HCD122. Tumor growth was followed up until Day 14. Molecular imaging with FLT-PET was performed before (Day 0) and after start of therapy (Day 2 and Day 7). On Day 14 lymphoma xenografts were explanted for immunohistochemical analysis to correlate PET findings with CD40 surface expression on tumor tissue. Results: Treatment with HCD122 significantly delayed tumor growth resulting in a tumor growth inhibition of 45% on Day 14. Significant reduction of tumor-to-background ratio (TBR) of FLT-PET was seen in treated animals on Day 7 and preceded change of tumor volume, thus predicting therapy response to HCD122. Immunohistochemical analysis of xenografts revealed significantly higher CD40 expression on treated than on untreated tissue. Moreover, we found a significant correlation between CD40 expression and FLT-PET response for xenograft tumor treated with HCD122. Conclusions: Treatment of DLBCL with the antagonistic CD40 antibody HCD122 can be monitored with FLT-PET as early as seven days after commencement of therapy and seems to increase CD40 expression on tumor tissue.展开更多
Many industrial companies and researchers are looking for more efficient model driven engineering approaches (MDE) in software engineering of manufacturing automation systems (MS) especially for logic control programm...Many industrial companies and researchers are looking for more efficient model driven engineering approaches (MDE) in software engineering of manufacturing automation systems (MS) especially for logic control programming, but are uncertain about the applicability and effort needed to implement those approaches in comparison to classical Programmable Logic Controller?(PLC) programming with IEC 61131-3. The paper summarizes results of usability experiments evaluating UML and SysML as software engineering notations for a MDE applied in the domain of manufacturing systems. Modeling MS needs to cover the domain specific characteristics,?i.e.?hybrid process, real time requirements and communication requirements. In addition the paper presents factors, constraint and practical experience for the development of further usability experiments. The paper gives examples of notational expressiveness and weaknesses of UML and SysML. The appendix delivers detailed master models, representing the correct best suited model, and evaluation schemes of the experiment, which is helpful if setting up own empirical experiments.展开更多
Industry 4.0 and Cyber Physical Production Systems (CPPS) are often discussed and partially already sold. One important feature of CPPS is fault tolerance and as a consequence self-configuration and restart to increas...Industry 4.0 and Cyber Physical Production Systems (CPPS) are often discussed and partially already sold. One important feature of CPPS is fault tolerance and as a consequence self-configuration and restart to increase Overall Equipment Effectiveness. To understand this challenge at first the state of the art of fault handling in industrial automated production systems (aPS) is discussed as a result of a case study analysis in eight companies developing aPS. In the next step, metrics to evaluate the concept of self-configuration and restart for aPS focusing on real-time capabilities, fault coverage and effort to increase fault coverage are proposed. Finally, two different lab size case studies prove the applicability of the concepts of self-configuration, restart and the proposed metrics.展开更多
Recurrent Neural Networks were invented a long time ago, and dozens of different architectures have been published. In this paper we generalize recurrent architectures to a state space model, and we also generalize th...Recurrent Neural Networks were invented a long time ago, and dozens of different architectures have been published. In this paper we generalize recurrent architectures to a state space model, and we also generalize the numbers the network can process to the complex domain. We show how to train the recurrent network in the complex valued case, and we present the theorems and procedures to make the training stable. We also show that the complex valued recurrent neural network is a generalization of the real valued counterpart and that it has specific advantages over the latter. We conclude the paper with a discussion of possible applications and scenarios for using these networks.展开更多
Nitrogen rate trials are often performed to determine the economically optimum N application rate. For this purpose, the yield is modeled as a function of the N application. The regression analysis provides an estimat...Nitrogen rate trials are often performed to determine the economically optimum N application rate. For this purpose, the yield is modeled as a function of the N application. The regression analysis provides an estimate of the modeled function and thus also an estimate of the economic optimum, Nopt. Obtaining the accuracy of such estimates by confidence intervals for Nopt is subject to the model assumptions. The dependence of these assumptions is a further source of inaccuracy. The Nopt estimate also strongly depends on the N level design, i.e., the area on which the model is fitted. A small area around the supposed Nopt diminishes the dependence of the model assumptions, but prolongs the confidence interval. The investigations of the impact of the mentioned sources on the inaccuracy of the Nopt estimate rely on N rate trials on the experimental field Sieblerfeld (Bavaria). The models applied are the quadratic and the linear-plus-plateau yield regression model.展开更多
Cigarette consumption increases oxidative stress in many organs. Increased oxidative stress harms bone cells, which negatively affects bone-matter and -stability. This leads to an increased fracture risk and delayed f...Cigarette consumption increases oxidative stress in many organs. Increased oxidative stress harms bone cells, which negatively affects bone-matter and -stability. This leads to an increased fracture risk and delayed fracture healing in smokers. A supporting therapy with antioxidants could be of great benefit for surgeons dealing with delayed fracture healing due to increased oxidative stress. In this article we complement and compare our published data with hitherto unpublished data and show the protective effect of 15 different antioxidants on cigarette smoke induced damage in primary human osteoblasts. Exposure to cigarette smoke medium (CSM) rapidly induces formation of ROS in osteoblasts in a concentration- and time-dependent manner. Massive cell damage is seen already after 4 h (EC50 ≈ 0.75 OD320). Pre-, co- and post-incubation with the different antioxidants reduces the formation of ROS and consequently improves the viability of the CSM exposed osteoblasts. Small compounds, e.g. N-acetylcysteine, proved highly effective if pre- or co-incubated before exposure to the CSM. Thus, they are good candidates for acute therapy support as they can be administered in high doses. However, our data suggest that a balanced daily diet could lead to an accumulation of various natural antioxidants (flavonoids) that effectively protect osteoblasts from oxidative stress-induced damage in all three settings investigated. Together with their partly phytoestrogenic properties this may even abate alterations in bone and thus reduce fracture risk on the long run.展开更多
Previous clinical study showed that aged garlic extract (AGE) has a preventive effect of vascular calcification in patients with coronary artery diseases. It has been reported that vascular smooth muscle cells (VSMC) ...Previous clinical study showed that aged garlic extract (AGE) has a preventive effect of vascular calcification in patients with coronary artery diseases. It has been reported that vascular smooth muscle cells (VSMC) and inflammatory cells including macrophages and lymphocytes migrate to sub-intimal region where atherosclerotic plaques are formed, and VSMC can differentiate into osteoblast-like cells, which are represented by the induction of alkaline phosphatase (ALP). We found that primary human coronary artery smooth muscle cells (HCASMC) showed the increased ALP activity, when cultured in the medium containing ascorbic acid, β-glycerophosphate, dexamethasone (IM), and supplemented with conditioned medium from macrophages (MCM). Then we tested the effect of AGE subdivided fractions and several compounds found in AGE, and then found that ((+)-(2S,3R)-Dehydrodiconiferyl alcohol, a dilignol compound existed in hydrophobic fraction of AGE, inhibited ALP activity in HCASMC.展开更多
We report a very rare case of successful intracardiac correction in a patient with heterotaxy syndrome.The cardiac malformations included dextrocardia,double outlet right ventricle,pulmonary stenosis,interrupted infer...We report a very rare case of successful intracardiac correction in a patient with heterotaxy syndrome.The cardiac malformations included dextrocardia,double outlet right ventricle,pulmonary stenosis,interrupted inferior vena cava,hemiazygos continuation and total anomalous pulmonary venous return.One-stage correction was performed.The atrial procedure consisted of intra-and extraatrial rerouting of the anomalous systemic and pulmonary venous return.The hepatic veins were detached and diverted to the left atrium via an extracardiac conduit.The correction of the double outlet right ventricle was accomplished by intraventricular redirection of the blood flow from the left ventricle to the aorta.The right ventricular outflow was ultimately remodeled using a valved conduit.For better perception of the complex morphology,a three-dimensional model was designed,using CT scan images.This proved to be very useful for surgical planning,especially with regard to the intraatrial reconstruction of the systemic and pulmonary venous rerouting.展开更多
Ambrosia artemisiifolia L. (common ragweed) is an annual ruderal plant that is native to Northern America but nowadays is also spreading across Europe, and its pollen is known to be highly allergenic. Air pollution, e...Ambrosia artemisiifolia L. (common ragweed) is an annual ruderal plant that is native to Northern America but nowadays is also spreading across Europe, and its pollen is known to be highly allergenic. Air pollution, e.g. NOx and climate change may affect the plant growth, pollen production and duration of the entire pollen season. In this study, ragweed plants were grown over an entire vegetation period under 40 ppb NO2/clean air (control) and 80 ppb NO2 (treatment). The inflorescence length was not affected by this air pollutant. However, the pollen amount increased, while the seed production decreased in both populations upon elevated NO2 concentrations. Regarding phenolic metabolites elevated NO2 had no effect on the amount of total phenolic metabolites, while individual metabolites showed significant changes.展开更多
The yield map is generated by fitting the yield surface shape of yield monitor data mainly using paraboloid cones on floating neighborhoods. Each yield map value is determined by the fit of such a cone on an elliptica...The yield map is generated by fitting the yield surface shape of yield monitor data mainly using paraboloid cones on floating neighborhoods. Each yield map value is determined by the fit of such a cone on an elliptical neighborhood that is wider across the harvest tracks than it is along them. The coefficients of regression for modeling the paraboloid cones and the scale parameter are estimated using robust weighted M-estimators where the weights decrease quadratically from 1 in the middle to zero at the border of the selected neighborhood. The robust way of estimating the model parameters supersedes a procedure for detecting outliers. For a given neighborhood shape, this yield mapping method is implemented by the Fortran program paraboloidmapping.exe, which can be downloaded from the web. The size of the selected neighborhood is considered appropriate if the variance of the yield map values equals the variance of the true yields, which is the difference between the variance of the raw yield data and the error variance of the yield monitor. It is estimated using a robust variogram on data that have not had the trend removed.展开更多
As production automation systems have been and are becoming more and more complex, the task of quality assurance is increasingly challenging. Model-based testing is a research field addressing this challenge and many ...As production automation systems have been and are becoming more and more complex, the task of quality assurance is increasingly challenging. Model-based testing is a research field addressing this challenge and many approaches have been suggested for different applications. The goal of this paper is to review these approaches regarding their suitability for the domain of production automation in order to identify current trends and research gaps. The different approaches are classified and clustered according to their main focus which is either testing and test case generation from some form of model automatons, test case generation from models used within the development process of production automation systems, test case generation from fault models or test case selection and regression testing.展开更多
Proanthocyanidins and flavanoids, both subfamilies of the polyphenols, are highly concentrated in different fruits and berries as well as in fruit pomace. They have shown to exhibit anti-cancer, anti-microbial, anti-o...Proanthocyanidins and flavanoids, both subfamilies of the polyphenols, are highly concentrated in different fruits and berries as well as in fruit pomace. They have shown to exhibit anti-cancer, anti-microbial, anti-oxidative, and im- mune-modulatory effects in vertebrates. Herein the effect of additional apple pomace or red-grape pomace in conven- tional piglet starter feeds were investigated in 36 young growing piglets. Immunological marker gene expression was quantified by quantitative real-time RT-PCR in white blood cells, and intestinal bacterial flora was investigated from weaning to three weeks post weaning. Polyphenol content in red-grape pomace, gut content and tissues were analyzed with HPLC. Flavan-3-ols (epicatechin and catechin) and proanthocyanidins (B1, B2 and C1) were identified in the gas- tro-intestinal tract content, whereas only traces could be detected in various piglet organs. The blood parameters, he- moglobin and hematocrit, were affected and down-regulated in all groups over testing period. In both pomace treated groups more thrombocytes were present compared to the standard feeding group. It turns out, that the pomace diets had greatest impact on the bacterial content in the colon. Results demonstrate that feeding apple pomace and red- grape pomace tended to increase the number of total colonic bacteria. Steptococci/Enterococci increased in the red- grape pomace. C. perfringens was not detectable at the second time point. The number of lactobacilli increased in both applied diets. The number of Clostridium perfringens decreased with the age of the piglets. Trends of mRNA expression changes were found in white blood cell (WBC) between different feeding regimens, since the expression variability in the groups was very high. Between the different time points there were significant differences within the apple pomace group, where TNF? (p = 0.033), NF?B (p = 0.024) and Caspase 3 (p = 0.019) mRNA expression increased signifi- cantly during treatment. We conclude that both polyphenol rich feedings have the potential to positively influence the intestinal flora, blood parameters, and WBC mRNA gene expression pattern of immunological marker genes.展开更多
This paper gives an introduction to the essential challenges of software engineering and requirements that software has to fulfill in the domain of automation. Besides, the functional characteristics, specific constra...This paper gives an introduction to the essential challenges of software engineering and requirements that software has to fulfill in the domain of automation. Besides, the functional characteristics, specific constraints and circumstances are considered for deriving requirements concerning usability, the technical process, the automation functions, used platform and the well-established models, which are described in detail. On the other hand, challenges result from the circumstances at different points in the single phases of the life cycle of the automated system. The requirements for life-cycle-management, tools and the changeability during runtime are described in detail.展开更多
The COST Action FP0903 “Climate Change and Forest Mitigation and Adaptation in a Polluted Environment (MAFor)” involved 29 countries and created a platform for information exchange with experts from different fields...The COST Action FP0903 “Climate Change and Forest Mitigation and Adaptation in a Polluted Environment (MAFor)” involved 29 countries and created a platform for information exchange with experts from different fields, with the following main objectives: 1) to increase understanding of the state and potential of forest mitigation and adaptation to climate change in a polluted environment and 2) to reconcile process-oriented research, long-term monitoring and applied modelling at comprehensive forest research sites. In particular, MAFor translated the existing European knowledge on climate and air pollution dynamics into prospects for forest research and monitoring, with focus on the carbon, ozone, nitrogen and water budgets. The aim of this paper is to summarize scientific activities and achievements of MAFor: the creation of a meta-database for highlighting the available data and integrating the information from European forest research/monitoring networks;the development of a new concept of forest sites for research and monitoring (Supersites);the identification of the main knowledge gaps;and the definition of priorities for forest adaptation to climate change in a polluted environment. The action also increased European capacity building in this sector by organizing five conferences, granting 64 short-term scientific missions, organizing four training schools and publishing more than 100 papers.展开更多
Using a nonlocal version of the Polyakov-loop-extended Nambu-Jona-Lasinio model, we investigate effects of a nonderivative vector-current interaction (relating to the quark-number density) at both real and imaginary c...Using a nonlocal version of the Polyakov-loop-extended Nambu-Jona-Lasinio model, we investigate effects of a nonderivative vector-current interaction (relating to the quark-number density) at both real and imaginary chemical potentials. This repulsive vector interaction between quarks has the following impact on the chiral first-order phase transition: at imaginary chemical potential it sharpens the transition at the Roberge-Weiss (RW) end point and moves this critical point toward lower temperatures;at real chemical potential, the critical end point moves on a trajectory towards larger chemical potentials and lower temperatures with increasing vector coupling strength. The conditions are discussed at which the first-order phase transition disappears and turns into a smooth crossover.展开更多
Furazan and furoxan represent fascinating explosophoric units with intriguing structures and unique properties.Compared with other nitrogen-rich heterocycles,most poly furazan and furoxan-based heterocycles demonstrat...Furazan and furoxan represent fascinating explosophoric units with intriguing structures and unique properties.Compared with other nitrogen-rich heterocycles,most poly furazan and furoxan-based heterocycles demonstrate superior energetic performances due to the higher enthalpy of formation and density levels.A large variety of advanced energetic materials have been achieved based on the combination of furazan and furoxan moieties with different kinds of linkers and this review provides an overview of the development of energetic poly furazan and furoxan structures during the past decades,with their physical properties and detonation characteristics summarized and compa red with traditional energetic materials.Various synthetic strategies towards these compact energetic structures are highlighted by covering the most important cyclization methods for construction of the hetercyclic scaffolds and the following modifications such as nitrations and oxidations.Given the synthetic availabilities and outstanding properties,energetic materials based on poly furazan and furoxan structures are undoubtedly listed as a promising candidate for the development of new-generation explosives,propellants and pyrotechnics.展开更多
Plants have evolved sophisticated defense mechanisms to overcome their sessile nature.However,if and how volatiles from cold‐stressed plants can trigger interplant communication is still unknown.Here,we provide the f...Plants have evolved sophisticated defense mechanisms to overcome their sessile nature.However,if and how volatiles from cold‐stressed plants can trigger interplant communication is still unknown.Here,we provide the first evidence for interplant communication via inducible volatiles in cold stress.The volatiles,including nerolidol,geraniol,linalool,and methyl salicylate,emitted from cold‐stressed tea plants play key role(s)in priming cold tolerance of their neighbors via a C‐repeatbinding factors‐dependent pathway.The knowledge will help us to understand how plants respond to volatile cues in cold stress and agricultural ecosystems.展开更多
文摘Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms.Due to the limited range of the a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.
文摘Background: Inhibition of the lymphoma surface antigen CD40 by the antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various lymphoma subtypes. In this preclinical in vivo study we examined the suitability of positron emission tomography (PET) using the thymidine analogue 3’-deoxy-3’-[18F]fluorothymidine (FLT) for early response assessment upon HCD122 treatment in diffuse large B cell lymphoma (DLBCL). Methods: Immunodeficient mice bearing human DLBCL xenografts (SU-DHL-4) received weekly intraperitoneal injections of HCD122. Tumor growth was followed up until Day 14. Molecular imaging with FLT-PET was performed before (Day 0) and after start of therapy (Day 2 and Day 7). On Day 14 lymphoma xenografts were explanted for immunohistochemical analysis to correlate PET findings with CD40 surface expression on tumor tissue. Results: Treatment with HCD122 significantly delayed tumor growth resulting in a tumor growth inhibition of 45% on Day 14. Significant reduction of tumor-to-background ratio (TBR) of FLT-PET was seen in treated animals on Day 7 and preceded change of tumor volume, thus predicting therapy response to HCD122. Immunohistochemical analysis of xenografts revealed significantly higher CD40 expression on treated than on untreated tissue. Moreover, we found a significant correlation between CD40 expression and FLT-PET response for xenograft tumor treated with HCD122. Conclusions: Treatment of DLBCL with the antagonistic CD40 antibody HCD122 can be monitored with FLT-PET as early as seven days after commencement of therapy and seems to increase CD40 expression on tumor tissue.
文摘Many industrial companies and researchers are looking for more efficient model driven engineering approaches (MDE) in software engineering of manufacturing automation systems (MS) especially for logic control programming, but are uncertain about the applicability and effort needed to implement those approaches in comparison to classical Programmable Logic Controller?(PLC) programming with IEC 61131-3. The paper summarizes results of usability experiments evaluating UML and SysML as software engineering notations for a MDE applied in the domain of manufacturing systems. Modeling MS needs to cover the domain specific characteristics,?i.e.?hybrid process, real time requirements and communication requirements. In addition the paper presents factors, constraint and practical experience for the development of further usability experiments. The paper gives examples of notational expressiveness and weaknesses of UML and SysML. The appendix delivers detailed master models, representing the correct best suited model, and evaluation schemes of the experiment, which is helpful if setting up own empirical experiments.
文摘Industry 4.0 and Cyber Physical Production Systems (CPPS) are often discussed and partially already sold. One important feature of CPPS is fault tolerance and as a consequence self-configuration and restart to increase Overall Equipment Effectiveness. To understand this challenge at first the state of the art of fault handling in industrial automated production systems (aPS) is discussed as a result of a case study analysis in eight companies developing aPS. In the next step, metrics to evaluate the concept of self-configuration and restart for aPS focusing on real-time capabilities, fault coverage and effort to increase fault coverage are proposed. Finally, two different lab size case studies prove the applicability of the concepts of self-configuration, restart and the proposed metrics.
文摘Recurrent Neural Networks were invented a long time ago, and dozens of different architectures have been published. In this paper we generalize recurrent architectures to a state space model, and we also generalize the numbers the network can process to the complex domain. We show how to train the recurrent network in the complex valued case, and we present the theorems and procedures to make the training stable. We also show that the complex valued recurrent neural network is a generalization of the real valued counterpart and that it has specific advantages over the latter. We conclude the paper with a discussion of possible applications and scenarios for using these networks.
文摘Nitrogen rate trials are often performed to determine the economically optimum N application rate. For this purpose, the yield is modeled as a function of the N application. The regression analysis provides an estimate of the modeled function and thus also an estimate of the economic optimum, Nopt. Obtaining the accuracy of such estimates by confidence intervals for Nopt is subject to the model assumptions. The dependence of these assumptions is a further source of inaccuracy. The Nopt estimate also strongly depends on the N level design, i.e., the area on which the model is fitted. A small area around the supposed Nopt diminishes the dependence of the model assumptions, but prolongs the confidence interval. The investigations of the impact of the mentioned sources on the inaccuracy of the Nopt estimate rely on N rate trials on the experimental field Sieblerfeld (Bavaria). The models applied are the quadratic and the linear-plus-plateau yield regression model.
文摘Cigarette consumption increases oxidative stress in many organs. Increased oxidative stress harms bone cells, which negatively affects bone-matter and -stability. This leads to an increased fracture risk and delayed fracture healing in smokers. A supporting therapy with antioxidants could be of great benefit for surgeons dealing with delayed fracture healing due to increased oxidative stress. In this article we complement and compare our published data with hitherto unpublished data and show the protective effect of 15 different antioxidants on cigarette smoke induced damage in primary human osteoblasts. Exposure to cigarette smoke medium (CSM) rapidly induces formation of ROS in osteoblasts in a concentration- and time-dependent manner. Massive cell damage is seen already after 4 h (EC50 ≈ 0.75 OD320). Pre-, co- and post-incubation with the different antioxidants reduces the formation of ROS and consequently improves the viability of the CSM exposed osteoblasts. Small compounds, e.g. N-acetylcysteine, proved highly effective if pre- or co-incubated before exposure to the CSM. Thus, they are good candidates for acute therapy support as they can be administered in high doses. However, our data suggest that a balanced daily diet could lead to an accumulation of various natural antioxidants (flavonoids) that effectively protect osteoblasts from oxidative stress-induced damage in all three settings investigated. Together with their partly phytoestrogenic properties this may even abate alterations in bone and thus reduce fracture risk on the long run.
文摘Previous clinical study showed that aged garlic extract (AGE) has a preventive effect of vascular calcification in patients with coronary artery diseases. It has been reported that vascular smooth muscle cells (VSMC) and inflammatory cells including macrophages and lymphocytes migrate to sub-intimal region where atherosclerotic plaques are formed, and VSMC can differentiate into osteoblast-like cells, which are represented by the induction of alkaline phosphatase (ALP). We found that primary human coronary artery smooth muscle cells (HCASMC) showed the increased ALP activity, when cultured in the medium containing ascorbic acid, β-glycerophosphate, dexamethasone (IM), and supplemented with conditioned medium from macrophages (MCM). Then we tested the effect of AGE subdivided fractions and several compounds found in AGE, and then found that ((+)-(2S,3R)-Dehydrodiconiferyl alcohol, a dilignol compound existed in hydrophobic fraction of AGE, inhibited ALP activity in HCASMC.
文摘We report a very rare case of successful intracardiac correction in a patient with heterotaxy syndrome.The cardiac malformations included dextrocardia,double outlet right ventricle,pulmonary stenosis,interrupted inferior vena cava,hemiazygos continuation and total anomalous pulmonary venous return.One-stage correction was performed.The atrial procedure consisted of intra-and extraatrial rerouting of the anomalous systemic and pulmonary venous return.The hepatic veins were detached and diverted to the left atrium via an extracardiac conduit.The correction of the double outlet right ventricle was accomplished by intraventricular redirection of the blood flow from the left ventricle to the aorta.The right ventricular outflow was ultimately remodeled using a valved conduit.For better perception of the complex morphology,a three-dimensional model was designed,using CT scan images.This proved to be very useful for surgical planning,especially with regard to the intraatrial reconstruction of the systemic and pulmonary venous rerouting.
文摘Ambrosia artemisiifolia L. (common ragweed) is an annual ruderal plant that is native to Northern America but nowadays is also spreading across Europe, and its pollen is known to be highly allergenic. Air pollution, e.g. NOx and climate change may affect the plant growth, pollen production and duration of the entire pollen season. In this study, ragweed plants were grown over an entire vegetation period under 40 ppb NO2/clean air (control) and 80 ppb NO2 (treatment). The inflorescence length was not affected by this air pollutant. However, the pollen amount increased, while the seed production decreased in both populations upon elevated NO2 concentrations. Regarding phenolic metabolites elevated NO2 had no effect on the amount of total phenolic metabolites, while individual metabolites showed significant changes.
文摘The yield map is generated by fitting the yield surface shape of yield monitor data mainly using paraboloid cones on floating neighborhoods. Each yield map value is determined by the fit of such a cone on an elliptical neighborhood that is wider across the harvest tracks than it is along them. The coefficients of regression for modeling the paraboloid cones and the scale parameter are estimated using robust weighted M-estimators where the weights decrease quadratically from 1 in the middle to zero at the border of the selected neighborhood. The robust way of estimating the model parameters supersedes a procedure for detecting outliers. For a given neighborhood shape, this yield mapping method is implemented by the Fortran program paraboloidmapping.exe, which can be downloaded from the web. The size of the selected neighborhood is considered appropriate if the variance of the yield map values equals the variance of the true yields, which is the difference between the variance of the raw yield data and the error variance of the yield monitor. It is estimated using a robust variogram on data that have not had the trend removed.
文摘As production automation systems have been and are becoming more and more complex, the task of quality assurance is increasingly challenging. Model-based testing is a research field addressing this challenge and many approaches have been suggested for different applications. The goal of this paper is to review these approaches regarding their suitability for the domain of production automation in order to identify current trends and research gaps. The different approaches are classified and clustered according to their main focus which is either testing and test case generation from some form of model automatons, test case generation from models used within the development process of production automation systems, test case generation from fault models or test case selection and regression testing.
基金This study was supported by the Bayerisches Staatsmin-isterium für Landwirtschaft und Forsten,L/a-7606.2-494.
文摘Proanthocyanidins and flavanoids, both subfamilies of the polyphenols, are highly concentrated in different fruits and berries as well as in fruit pomace. They have shown to exhibit anti-cancer, anti-microbial, anti-oxidative, and im- mune-modulatory effects in vertebrates. Herein the effect of additional apple pomace or red-grape pomace in conven- tional piglet starter feeds were investigated in 36 young growing piglets. Immunological marker gene expression was quantified by quantitative real-time RT-PCR in white blood cells, and intestinal bacterial flora was investigated from weaning to three weeks post weaning. Polyphenol content in red-grape pomace, gut content and tissues were analyzed with HPLC. Flavan-3-ols (epicatechin and catechin) and proanthocyanidins (B1, B2 and C1) were identified in the gas- tro-intestinal tract content, whereas only traces could be detected in various piglet organs. The blood parameters, he- moglobin and hematocrit, were affected and down-regulated in all groups over testing period. In both pomace treated groups more thrombocytes were present compared to the standard feeding group. It turns out, that the pomace diets had greatest impact on the bacterial content in the colon. Results demonstrate that feeding apple pomace and red- grape pomace tended to increase the number of total colonic bacteria. Steptococci/Enterococci increased in the red- grape pomace. C. perfringens was not detectable at the second time point. The number of lactobacilli increased in both applied diets. The number of Clostridium perfringens decreased with the age of the piglets. Trends of mRNA expression changes were found in white blood cell (WBC) between different feeding regimens, since the expression variability in the groups was very high. Between the different time points there were significant differences within the apple pomace group, where TNF? (p = 0.033), NF?B (p = 0.024) and Caspase 3 (p = 0.019) mRNA expression increased signifi- cantly during treatment. We conclude that both polyphenol rich feedings have the potential to positively influence the intestinal flora, blood parameters, and WBC mRNA gene expression pattern of immunological marker genes.
文摘This paper gives an introduction to the essential challenges of software engineering and requirements that software has to fulfill in the domain of automation. Besides, the functional characteristics, specific constraints and circumstances are considered for deriving requirements concerning usability, the technical process, the automation functions, used platform and the well-established models, which are described in detail. On the other hand, challenges result from the circumstances at different points in the single phases of the life cycle of the automated system. The requirements for life-cycle-management, tools and the changeability during runtime are described in detail.
基金Support by the COST Action FP0903“Climate change and forest mitigation and adaptation in the polluted environment”
文摘The COST Action FP0903 “Climate Change and Forest Mitigation and Adaptation in a Polluted Environment (MAFor)” involved 29 countries and created a platform for information exchange with experts from different fields, with the following main objectives: 1) to increase understanding of the state and potential of forest mitigation and adaptation to climate change in a polluted environment and 2) to reconcile process-oriented research, long-term monitoring and applied modelling at comprehensive forest research sites. In particular, MAFor translated the existing European knowledge on climate and air pollution dynamics into prospects for forest research and monitoring, with focus on the carbon, ozone, nitrogen and water budgets. The aim of this paper is to summarize scientific activities and achievements of MAFor: the creation of a meta-database for highlighting the available data and integrating the information from European forest research/monitoring networks;the development of a new concept of forest sites for research and monitoring (Supersites);the identification of the main knowledge gaps;and the definition of priorities for forest adaptation to climate change in a polluted environment. The action also increased European capacity building in this sector by organizing five conferences, granting 64 short-term scientific missions, organizing four training schools and publishing more than 100 papers.
基金supported in part by BMBFby the Excellence Cluster“Origin and Structure of the Universe”by DFG and NSFC through CRC 110.
文摘Using a nonlocal version of the Polyakov-loop-extended Nambu-Jona-Lasinio model, we investigate effects of a nonderivative vector-current interaction (relating to the quark-number density) at both real and imaginary chemical potentials. This repulsive vector interaction between quarks has the following impact on the chiral first-order phase transition: at imaginary chemical potential it sharpens the transition at the Roberge-Weiss (RW) end point and moves this critical point toward lower temperatures;at real chemical potential, the critical end point moves on a trajectory towards larger chemical potentials and lower temperatures with increasing vector coupling strength. The conditions are discussed at which the first-order phase transition disappears and turns into a smooth crossover.
基金financial support from the financial support from the National Natural Science Foundation of China(Nos.21805223 and 21805226)the China Postdoctoral Science Foundation(No.2018M633552)the China Scholarship Council(No.201805290006)。
文摘Furazan and furoxan represent fascinating explosophoric units with intriguing structures and unique properties.Compared with other nitrogen-rich heterocycles,most poly furazan and furoxan-based heterocycles demonstrate superior energetic performances due to the higher enthalpy of formation and density levels.A large variety of advanced energetic materials have been achieved based on the combination of furazan and furoxan moieties with different kinds of linkers and this review provides an overview of the development of energetic poly furazan and furoxan structures during the past decades,with their physical properties and detonation characteristics summarized and compa red with traditional energetic materials.Various synthetic strategies towards these compact energetic structures are highlighted by covering the most important cyclization methods for construction of the hetercyclic scaffolds and the following modifications such as nitrations and oxidations.Given the synthetic availabilities and outstanding properties,energetic materials based on poly furazan and furoxan structures are undoubtedly listed as a promising candidate for the development of new-generation explosives,propellants and pyrotechnics.
基金supported by the National Key Research and Development Program of China(2018YFD1000601)National Natural Science Founda-tion of China(31961133030,31870678)Science Fundfor Distinguished Young Scientists of Anhui Province(1908085J12).
文摘Plants have evolved sophisticated defense mechanisms to overcome their sessile nature.However,if and how volatiles from cold‐stressed plants can trigger interplant communication is still unknown.Here,we provide the first evidence for interplant communication via inducible volatiles in cold stress.The volatiles,including nerolidol,geraniol,linalool,and methyl salicylate,emitted from cold‐stressed tea plants play key role(s)in priming cold tolerance of their neighbors via a C‐repeatbinding factors‐dependent pathway.The knowledge will help us to understand how plants respond to volatile cues in cold stress and agricultural ecosystems.
