AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （...AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （5-FC）, we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase （YCD） and the yeast uracil phosphoribosyltransferase （YUPRT） gene. RESULTS： In vitro stably transduced Morris rat hepatoma cells （MH） expressing the bifunctional SuperCD suicide gene （MH SuperCD） showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH cells stably expressing YCD solely （MH YCD） or the cytosine deaminase gene of bacterial origin （MH BCD）, respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions （P〈0.01） under both high dose as well as low dose systemic 5-FC application, whereas MH tumors without transgene expression （MH naive） showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness （SuperCD〉〉 YCD〉〉BCD〉〉〉negative control） was defined as a result of a direct in vivo comparison of all three suicide genes. CONCLUSION： Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.展开更多
For a climate-neutral future mobility,the socalled e-fuels can play an essential part.Especially,oxygenated e-fuels containing oxygen in their chemical formula have the additional potential to burn with significantly ...For a climate-neutral future mobility,the socalled e-fuels can play an essential part.Especially,oxygenated e-fuels containing oxygen in their chemical formula have the additional potential to burn with significantly lower soot levels.In particular,polyoxymethylene dimethyl ethers or oxymethylene ethers(PODEs or OMEs)do not contain carbon-carbon bonds,prohibiting the production of soot precursors like acetylene(C_(2)H_(2)).These properties make OMEs a highly interesting candidate for future climate-neutral compression-ignition engines.However,to fully leverage their potential,the auto-ignition process,flame propagation,and mixing regimes of the combustion need to be understood.To achieve this,efficient oxidation mechanisms suitable for computational fluid dynamics(CFD)calculations must be developed and validated.The present work aims to highlight the improvements made by developing an adapted oxidation mechanism for OME1-6 and introducing it into a validated spray combustion CFD model for OMEs.The simulations were conducted for single-and multi-injection patterns,changing ambient temperatures,and oxygen contents.The results were validated against high-pressure and high-temperature constantpressure chamber experiments.OH*-chemiluminescence measurements accomplished the characterization of the auto-ignition process.Both experiments and simulations were conducted for two different injectors.Significant improvements concerning the prediction of the ignition delay time were accomplished while also retaining an excellent agreement for the flame lift-off length.The spatial zones of high-temperature reaction activity were also affected by the adaption of the reaction kinetics.They showed a greater tendency to form OH^(*) radicals within the center of the spray in accordance with the experiments.展开更多
When was the last time music made the hairs on the back of your neck stand up,sent a chill doun your spine or gave you goosebumps all over?The first time that intoxicating sensation rattled Jeremy Wagner-a composer,le...When was the last time music made the hairs on the back of your neck stand up,sent a chill doun your spine or gave you goosebumps all over?The first time that intoxicating sensation rattled Jeremy Wagner-a composer,lecturer and thetechnical director ofthe Center forNewMusic&Audio Technologies at UC Berkeley-was during high school,when he was flooded with emotion while listening to the Beatles’1967 track“A Day in the Life.”展开更多
Chemical pesticides tend to accumulate in soil, resulting in human and environmental health risks. Hence, alternative methodologies involving chemical pesticides are beneficial for the control of agricultural pests. &...Chemical pesticides tend to accumulate in soil, resulting in human and environmental health risks. Hence, alternative methodologies involving chemical pesticides are beneficial for the control of agricultural pests. </span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">Metarhizium anisopliae</i></span></i> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">is an entomopathogenic fungus that acts on different developmental stages of pest insects such as <i></span><i><span style="font-family:Verdana;">Diatraea saccharalis</i></span></i><span style="font-family:Verdana;">, a holometabolic lepidopteran with high potential for infestation in sugarcane crops. The present study evaluated the biocontrol effect of <i></span><i><span style="font-family:Verdana;">M. anisopliae</i></span></i><span style="font-family:Verdana;"> isolates MT and E9 on <i></span><i><span style="font-family:Verdana;">D. saccharalis</i></span></i><span style="font-family:Verdana;"> eggs at different ages by investigating the external and internal morphological alterations in treated eggs. Conidial suspensions of <i></span><i><span style="font-family:Verdana;">M. anisopliae</i></span></i><span style="font-family:Verdana;"> isolated from MT and E9 at concentrations of 10<sup></span><sup><span style="font-family:Verdana;">7</span></sup><span style="font-family:Verdana;"></sup> conidia/mL were applied to eggs of <i></span><i><span style="font-family:Verdana;">D. saccharalis</i></span></i><span style="font-family:Verdana;"> aged 0, 24, 48, 72, 96 and 120 h. The eggs were observed every 24 h during development (0 h to 144 h). Samples were collected for observational, histological, and ultrastructural analyses. We found that the MT isolate caused 100% inviability of eggs aged 0 - 72 h, 144 h after the bioassays, while the effect of the E9 isolate varied between 49.40% and 93.75%. Melanization was observed on the periphery of the展开更多
The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens w...The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups（n515）. Fifteen specimens（group 1） were glazed and 15 specimens（group 2） were veneered with feldspathic ceramic and then glazed. Prior to grinding,maximum roughness depth（Rmax） values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 mm, 10 mm, and 7.5 mm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmaxvalues were determined. Differences between groups were examined using one-way analysis of variance（ANOVA）. The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing.It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces.展开更多
AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to deter...AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.METHODS Two hundred and sixty patients treated with SOF combination partners PR(n = 51), R(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were postliver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.RESULTS Two hundred and forty/256(93.7%) patients achieved SVR12(m ITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/n L, 88% post-liver transplantation, 95% for GT1 a, 93% for GT1 b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10(P < 0.0001), liver cirrhosis(P = 0.005) at baseline. In Interferonfree treatment GT3 had significantly lower SVR rates than GT1(P = 0.016). Side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/n L and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.展开更多
We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma...We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma-secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection. In conclusion, in most individuals, the CD8+T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses.展开更多
Background Endomyocardial biopsy （EMB） is an important tool when patients with inflammatoric cardiomyopathy （DCMi） are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Metho...Background Endomyocardial biopsy （EMB） is an important tool when patients with inflammatoric cardiomyopathy （DCMi） are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB （Group 1 〉 70 years, n = 85; Group 3 〈 70 years; n = 418） were compared to patients of the same age group without evi- dence of DCMi on EMB （Group 2 〉 70 years, n = 45; Group 4 〈 70 years; n = 147）. Results Among 24,275 patients treated at our institu- tion during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 （2.1%） patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ~ 2.8 years, mean ejection fraction was 38% q- 14%. On presentation, signs of hemody- namic compromise （NYHA functional class IIUIV, low cardiac output/index, and low cardiac power index） were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B 19 （PVB） was frequently encountered in both age groups （Group 1： 69.4% vs. Group 2： 59.6%）; detection of more than one viral genome was more frequent in Group 1 （21.2% vs. 11.2%; P = 0.02） whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients 〉 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed.展开更多
Airborne photographs can be expediently used in environmental monitoring; e.g., in the surveillance of the state of natural reserve areas, such as wetlands; or in the measurement and mapping of pollutants, such as oil...Airborne photographs can be expediently used in environmental monitoring; e.g., in the surveillance of the state of natural reserve areas, such as wetlands; or in the measurement and mapping of pollutants, such as oil spills on a lake or sea. A new and cost-effective platform of airborne remote sensing is the UAV （unmanned aerial vehicle） or drone. In this experimental work, aerial photos were made in Bakony Mountains using three UAVs equipped with small HD （high definition） cameras; resolution： 1,280 ~ 720 pixels. Within the framework of this work, a small lake was photographed, where the beginning of eutrophication was detected. This hardly can be observed from ground, however, it is visible on the aerial photos. The airborne surveillance of areas of ragweed （Ambrosia sp.） populations was also investigated. It was found that both UAVs are feasible for these tasks, and the application of these platforms for environmental monitoring is advantageous, especially in case of natural reserve areas since those are very silent and--contrary to big aircrafts and helicopters---do not disturb the ecology even in natural reserve areas and the people living there. Moreover, those could be operated in a very flexible and economic way, and the aerial photos taken are highly informative.展开更多
The most important parameter affecting ground-penetrating radar （GPR） measurements is the complex effective relative permittivity εr^＊,eff because it controls the propagation velocity and the reflection of GPR pul...The most important parameter affecting ground-penetrating radar （GPR） measurements is the complex effective relative permittivity εr^＊,eff because it controls the propagation velocity and the reflection of GPR pulses. Knowing εr^＊,eff of soils passed through by electromagnetic waves increases accuracy in soil thickness and interface identification. Complex effective relative permittivity εr^＊,eff= εr^＊,eff - jεr^＊,effof 25 soil samples with textures ranging from loamy sand to silty clay was measured using the two-electrode parallelplate method. The measurements were conducted at defined water contents for frequencies from 1 MHz to 3 GHz. The results confirm the frequency dependence of εr^＊,eff and show that the dielectric behavior of soil-water mixtures is a function of water content. Applying the experimental data of this study with predictions based on the empirical model by Toppet aL （1980）, we find that Topp et aL＇s curve tends to underestimate the real part of εr^＊,eff measured. Along with frequency and water content, soil texture and organic matter affect soil permittivity. Moreover, the real part of εr^＊,eff increases at higher dry bulk densities. Output from our calibration model enables us to predict εr^＊,eff for the soil samples which were tested under the actual in situ soil water content. This results in high accuracy of soil thickness prediction.展开更多
Background -The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomo...Background -The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography(PET) with fluorodeoxyglucose(FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. Methods and Results -We analyzed the survival of 765 consecutive patients(age 64±11 years, 80%men) with advanced left ventricular systolic dysfunction(ejection fraction ≤35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention(surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients(30%) underwent early intervention(188[25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42[5%] had percutaneous revascularization); 535(70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death(3-year mortality rate of 15%versus 35%, propensity adjusted hazard ratio 0.52, 95%CI 0.33 to 0.81, P=0.0004). Conclusions -Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.展开更多
The overall expectation of introducing Canonical Workflow for Experimental Research and FAIR digital objects(FDOs)can be summarised as reducing the gap between workflow technology and research practices to make experi...The overall expectation of introducing Canonical Workflow for Experimental Research and FAIR digital objects(FDOs)can be summarised as reducing the gap between workflow technology and research practices to make experimental work more efficient and improve FAIRness without adding administrative load on the researchers.In this document,we will describe,with the help of an example,how CWFR could work in detail and improve research procedures.We have chosen the example of"experiments with human subjects"which stretches from planning an experiment to storing the collected data in a repository.While we focus on experiments with human subjects,we are convinced that CWFR can be applied to many other data generation processes based on experiments.The main challenge is to identify repeating patterns in existing research practices that can be abstracted to create CWFR.In this document,we will include detailed examples from different disciplines to demonstrate that CWFR can be implemented without violating specific disciplinary or methodological requirements.We do not claim to be comprehensive in all aspects,since these examples are meant to prove the concept of CWFR.展开更多
AIM： To generate and characcerize the synthetic transoiptional control units for transcriptional targeting of the liver, thereby compensating for the lack of specificity of currently available gene therapeutic vector...AIM： To generate and characcerize the synthetic transoiptional control units for transcriptional targeting of the liver, thereby compensating for the lack of specificity of currently available gene therapeutic vector systems. METHODS： Synthetic transcriptional control unit constructs were generated and analyzed for transcriptional activities in different cell types by FACS quantification, semi-quantitative RT-PCR, and Western blotting. RESULTS： A new bifunctionally-enhanced green fluorescent protein （EGFP）/neor fusion gene cassette was generated, and could flexibly be used both for transcript quantification and for selection of stable cell clones. Then, numerous synthetic transcriptional control units consisting of a minimal promoter linked to “naturally” derived composite enhancer elements from liver-specific expressed genes or binding sites of liver-specific transcription factors were inserted upstream of this reporter cassette. Following liposome-mediated transfection, EGFP reporter protein quantification by FACS analysis identified constructs encoding multimerized composite elements of the apolipoprotein B100 （APOB） promoter or the ornithin transcarbamoylase （OTC） enhancer to exhibit maximum transcriptional activities in liver originating cell lines, but only background levels in non-liver originating cell lines. In contrast, constructs encoding only singular binding sites of liver-specific transcription factors, namely hepatocyte nuclear factor （HNF）, HNF3, HNF4, HNF5, or CAAT/enhancer binding protein （C/EBP） only achieved background levels of EGFP expression. Finally, both semi-quantitative RT-PCR and Western blotting analysis of Hep3B cells demonstrated maximum transcriptional activities for a multimeric 4xAPOB cassette construct, which fully complied with the dataobtained by initial FACS analysis CONCLUSION： Synthetic transcriptional control unit constructs not only exhibit a superb degree of structural compactness, but also provide new means for liver-directed expression o展开更多
基金Supported by grants from German Research Foundation (LA649-20-2)Federal Ministry of Education, Science, Research and Technology (Fo. 01KS9602, Fo. 01KV9532)Interdisciplinary Clinical Research Center (IZKF) Tubingen, and the fortune-program of the Medical Faculty of Eberhard-Karls-University Tubingen (F. 1281127)W.A.W. supported by a scholarship from Pinguin Foundation (Henkel KGaA)
文摘AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （5-FC）, we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase （YCD） and the yeast uracil phosphoribosyltransferase （YUPRT） gene. RESULTS： In vitro stably transduced Morris rat hepatoma cells （MH） expressing the bifunctional SuperCD suicide gene （MH SuperCD） showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH cells stably expressing YCD solely （MH YCD） or the cytosine deaminase gene of bacterial origin （MH BCD）, respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions （P〈0.01） under both high dose as well as low dose systemic 5-FC application, whereas MH tumors without transgene expression （MH naive） showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness （SuperCD〉〉 YCD〉〉BCD〉〉〉negative control） was defined as a result of a direct in vivo comparison of all three suicide genes. CONCLUSION： Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.
文摘For a climate-neutral future mobility,the socalled e-fuels can play an essential part.Especially,oxygenated e-fuels containing oxygen in their chemical formula have the additional potential to burn with significantly lower soot levels.In particular,polyoxymethylene dimethyl ethers or oxymethylene ethers(PODEs or OMEs)do not contain carbon-carbon bonds,prohibiting the production of soot precursors like acetylene(C_(2)H_(2)).These properties make OMEs a highly interesting candidate for future climate-neutral compression-ignition engines.However,to fully leverage their potential,the auto-ignition process,flame propagation,and mixing regimes of the combustion need to be understood.To achieve this,efficient oxidation mechanisms suitable for computational fluid dynamics(CFD)calculations must be developed and validated.The present work aims to highlight the improvements made by developing an adapted oxidation mechanism for OME1-6 and introducing it into a validated spray combustion CFD model for OMEs.The simulations were conducted for single-and multi-injection patterns,changing ambient temperatures,and oxygen contents.The results were validated against high-pressure and high-temperature constantpressure chamber experiments.OH*-chemiluminescence measurements accomplished the characterization of the auto-ignition process.Both experiments and simulations were conducted for two different injectors.Significant improvements concerning the prediction of the ignition delay time were accomplished while also retaining an excellent agreement for the flame lift-off length.The spatial zones of high-temperature reaction activity were also affected by the adaption of the reaction kinetics.They showed a greater tendency to form OH^(*) radicals within the center of the spray in accordance with the experiments.
文摘When was the last time music made the hairs on the back of your neck stand up,sent a chill doun your spine or gave you goosebumps all over?The first time that intoxicating sensation rattled Jeremy Wagner-a composer,lecturer and thetechnical director ofthe Center forNewMusic&Audio Technologies at UC Berkeley-was during high school,when he was flooded with emotion while listening to the Beatles’1967 track“A Day in the Life.”
文摘Chemical pesticides tend to accumulate in soil, resulting in human and environmental health risks. Hence, alternative methodologies involving chemical pesticides are beneficial for the control of agricultural pests. </span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">Metarhizium anisopliae</i></span></i> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">is an entomopathogenic fungus that acts on different developmental stages of pest insects such as <i></span><i><span style="font-family:Verdana;">Diatraea saccharalis</i></span></i><span style="font-family:Verdana;">, a holometabolic lepidopteran with high potential for infestation in sugarcane crops. The present study evaluated the biocontrol effect of <i></span><i><span style="font-family:Verdana;">M. anisopliae</i></span></i><span style="font-family:Verdana;"> isolates MT and E9 on <i></span><i><span style="font-family:Verdana;">D. saccharalis</i></span></i><span style="font-family:Verdana;"> eggs at different ages by investigating the external and internal morphological alterations in treated eggs. Conidial suspensions of <i></span><i><span style="font-family:Verdana;">M. anisopliae</i></span></i><span style="font-family:Verdana;"> isolated from MT and E9 at concentrations of 10<sup></span><sup><span style="font-family:Verdana;">7</span></sup><span style="font-family:Verdana;"></sup> conidia/mL were applied to eggs of <i></span><i><span style="font-family:Verdana;">D. saccharalis</i></span></i><span style="font-family:Verdana;"> aged 0, 24, 48, 72, 96 and 120 h. The eggs were observed every 24 h during development (0 h to 144 h). Samples were collected for observational, histological, and ultrastructural analyses. We found that the MT isolate caused 100% inviability of eggs aged 0 - 72 h, 144 h after the bioassays, while the effect of the E9 isolate varied between 49.40% and 93.75%. Melanization was observed on the periphery of the
基金Forschungsgemeinschaft Dental e.V. for supporting this study (project no. 3/2012)
文摘The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups（n515）. Fifteen specimens（group 1） were glazed and 15 specimens（group 2） were veneered with feldspathic ceramic and then glazed. Prior to grinding,maximum roughness depth（Rmax） values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 mm, 10 mm, and 7.5 mm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmaxvalues were determined. Differences between groups were examined using one-way analysis of variance（ANOVA）. The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing.It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces.
文摘AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.METHODS Two hundred and sixty patients treated with SOF combination partners PR(n = 51), R(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were postliver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.RESULTS Two hundred and forty/256(93.7%) patients achieved SVR12(m ITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/n L, 88% post-liver transplantation, 95% for GT1 a, 93% for GT1 b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10(P < 0.0001), liver cirrhosis(P = 0.005) at baseline. In Interferonfree treatment GT3 had significantly lower SVR rates than GT1(P = 0.016). Side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/n L and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.
文摘We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma-secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection. In conclusion, in most individuals, the CD8+T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses.
文摘Background Endomyocardial biopsy （EMB） is an important tool when patients with inflammatoric cardiomyopathy （DCMi） are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB （Group 1 〉 70 years, n = 85; Group 3 〈 70 years; n = 418） were compared to patients of the same age group without evi- dence of DCMi on EMB （Group 2 〉 70 years, n = 45; Group 4 〈 70 years; n = 147）. Results Among 24,275 patients treated at our institu- tion during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 （2.1%） patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ~ 2.8 years, mean ejection fraction was 38% q- 14%. On presentation, signs of hemody- namic compromise （NYHA functional class IIUIV, low cardiac output/index, and low cardiac power index） were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B 19 （PVB） was frequently encountered in both age groups （Group 1： 69.4% vs. Group 2： 59.6%）; detection of more than one viral genome was more frequent in Group 1 （21.2% vs. 11.2%; P = 0.02） whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients 〉 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed.
文摘Airborne photographs can be expediently used in environmental monitoring; e.g., in the surveillance of the state of natural reserve areas, such as wetlands; or in the measurement and mapping of pollutants, such as oil spills on a lake or sea. A new and cost-effective platform of airborne remote sensing is the UAV （unmanned aerial vehicle） or drone. In this experimental work, aerial photos were made in Bakony Mountains using three UAVs equipped with small HD （high definition） cameras; resolution： 1,280 ~ 720 pixels. Within the framework of this work, a small lake was photographed, where the beginning of eutrophication was detected. This hardly can be observed from ground, however, it is visible on the aerial photos. The airborne surveillance of areas of ragweed （Ambrosia sp.） populations was also investigated. It was found that both UAVs are feasible for these tasks, and the application of these platforms for environmental monitoring is advantageous, especially in case of natural reserve areas since those are very silent and--contrary to big aircrafts and helicopters---do not disturb the ecology even in natural reserve areas and the people living there. Moreover, those could be operated in a very flexible and economic way, and the aerial photos taken are highly informative.
基金supported by the German Research Foundation (DFG) (No. SFB 299)
文摘The most important parameter affecting ground-penetrating radar （GPR） measurements is the complex effective relative permittivity εr^＊,eff because it controls the propagation velocity and the reflection of GPR pulses. Knowing εr^＊,eff of soils passed through by electromagnetic waves increases accuracy in soil thickness and interface identification. Complex effective relative permittivity εr^＊,eff= εr^＊,eff - jεr^＊,effof 25 soil samples with textures ranging from loamy sand to silty clay was measured using the two-electrode parallelplate method. The measurements were conducted at defined water contents for frequencies from 1 MHz to 3 GHz. The results confirm the frequency dependence of εr^＊,eff and show that the dielectric behavior of soil-water mixtures is a function of water content. Applying the experimental data of this study with predictions based on the empirical model by Toppet aL （1980）, we find that Topp et aL＇s curve tends to underestimate the real part of εr^＊,eff measured. Along with frequency and water content, soil texture and organic matter affect soil permittivity. Moreover, the real part of εr^＊,eff increases at higher dry bulk densities. Output from our calibration model enables us to predict εr^＊,eff for the soil samples which were tested under the actual in situ soil water content. This results in high accuracy of soil thickness prediction.
文摘Background -The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography(PET) with fluorodeoxyglucose(FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. Methods and Results -We analyzed the survival of 765 consecutive patients(age 64±11 years, 80%men) with advanced left ventricular systolic dysfunction(ejection fraction ≤35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention(surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients(30%) underwent early intervention(188[25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42[5%] had percutaneous revascularization); 535(70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death(3-year mortality rate of 15%versus 35%, propensity adjusted hazard ratio 0.52, 95%CI 0.33 to 0.81, P=0.0004). Conclusions -Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.
文摘The overall expectation of introducing Canonical Workflow for Experimental Research and FAIR digital objects(FDOs)can be summarised as reducing the gap between workflow technology and research practices to make experimental work more efficient and improve FAIRness without adding administrative load on the researchers.In this document,we will describe,with the help of an example,how CWFR could work in detail and improve research procedures.We have chosen the example of"experiments with human subjects"which stretches from planning an experiment to storing the collected data in a repository.While we focus on experiments with human subjects,we are convinced that CWFR can be applied to many other data generation processes based on experiments.The main challenge is to identify repeating patterns in existing research practices that can be abstracted to create CWFR.In this document,we will include detailed examples from different disciplines to demonstrate that CWFR can be implemented without violating specific disciplinary or methodological requirements.We do not claim to be comprehensive in all aspects,since these examples are meant to prove the concept of CWFR.
基金Supported by German Research Foundation (LA 649/11-1)Fortüne-program of the Medical Faculty of the Eberhard-Karls-University Tubingen (F.128101.1) Scholarship from the Pinguin Foundation (Henkel KGaA)
文摘AIM： To generate and characcerize the synthetic transoiptional control units for transcriptional targeting of the liver, thereby compensating for the lack of specificity of currently available gene therapeutic vector systems. METHODS： Synthetic transcriptional control unit constructs were generated and analyzed for transcriptional activities in different cell types by FACS quantification, semi-quantitative RT-PCR, and Western blotting. RESULTS： A new bifunctionally-enhanced green fluorescent protein （EGFP）/neor fusion gene cassette was generated, and could flexibly be used both for transcript quantification and for selection of stable cell clones. Then, numerous synthetic transcriptional control units consisting of a minimal promoter linked to “naturally” derived composite enhancer elements from liver-specific expressed genes or binding sites of liver-specific transcription factors were inserted upstream of this reporter cassette. Following liposome-mediated transfection, EGFP reporter protein quantification by FACS analysis identified constructs encoding multimerized composite elements of the apolipoprotein B100 （APOB） promoter or the ornithin transcarbamoylase （OTC） enhancer to exhibit maximum transcriptional activities in liver originating cell lines, but only background levels in non-liver originating cell lines. In contrast, constructs encoding only singular binding sites of liver-specific transcription factors, namely hepatocyte nuclear factor （HNF）, HNF3, HNF4, HNF5, or CAAT/enhancer binding protein （C/EBP） only achieved background levels of EGFP expression. Finally, both semi-quantitative RT-PCR and Western blotting analysis of Hep3B cells demonstrated maximum transcriptional activities for a multimeric 4xAPOB cassette construct, which fully complied with the dataobtained by initial FACS analysis CONCLUSION： Synthetic transcriptional control unit constructs not only exhibit a superb degree of structural compactness, but also provide new means for liver-directed expression o
