AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the i...AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.展开更多
Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible o...Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.展开更多
Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male dev...Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.展开更多
Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (...Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P <0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF,P <0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA,which may profoundly influence the development of AAA.展开更多
Mesoporous bioactive glasses(MBGs)are promising materials for regenerative medicine,due to their favorable properties including bioactivity and degradability.These key properties,but also their surface area,pore struc...Mesoporous bioactive glasses(MBGs)are promising materials for regenerative medicine,due to their favorable properties including bioactivity and degradability.These key properties,but also their surface area,pore structure and pore volume are strongly dependent on synthesis parameters and glass stoichiometry.However,to date no systematic study on MBG properties covering a broad range of possible compositions exists.Here,24 MBG compositions in the SiO_(2)-CaO-P_(2)O_(5) system were synthesized by varying SiO_(2)(60-90 mol%),CaO and P_(2)O_(5) content(both 0 to 40 mol-%),while other synthesis parameters were kept constant.Mesopore characteristics,degradability and bioactivity were analysed.The results showed that,within the tested range of compositions,mesopore formation required a molar SiO_(2) content above 60%but was independent of CaO and P_(2)O_(5) content.While mesopore size did not depend on glass stoichiometry,mesopore arrangement was influenced by the SiO_(2) content.Specific surface area and pore volume were slightly altered by the SiO_(2) content.All materials were degradable;however,degradation as well as bioactivity,i.e.the ability to form a CaP mineral on the surface,depended on stoichiometry.Major differences were found in early surface reactions in simulated body fluid:where some MBGs induced direct hydroxyapatite crystallization,high release of calcium in others resulted in calcite formation.In summary,degradation and bioactivity,both key parameters of MBGs,can be controlled by glass stoichiometry over a broad range while leaving the unique structural parameters of MBGs relatively unaffected.This allows targeted selection of material compositions for specific regenerative medicine applications.展开更多
Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and se...Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and serious complications such as tissue necrosis and osteomyelitis, can result without the timely control of infections. Recent studies have also reported an increase in the association of fungal infections with chronic non-healing ulcers. Aim: To determine the prevalence of bacterial and fungal infections among patients reporting with chronic leg ulcers in participants without co-morbidities. Methods: A prospective cross-sectional study was conducted among patients with chronic leg ulcers at the National Reconstructive Plastic Surgery and Burns Centre, Korle-Bu Teaching Hospital (NRPS/BC-KBTH) and those who consented were enrolled. Characteristics of the wound as well as micro-organisms cultured from wound swabs were recorded. Results: A total of 50 participants were enrolled for the study with the mean (SD) age of 40.7 (10.7) years. Eighty percent of the participants presented with post traumatic leg ulcers with 80% being artisans and traders in the age group 31 - 50 years. There was no statistically significant association between sex and the organism cultured for post traumatic and cellulitis (p-value > 0.05). The prevalence of bacterial and fungal infection was 79.3% and 20.7% respectively. Pseudomonas species was the most isolated bacteria (61.5%) while Aspergillus niger was the most isolated fungi (41%). Conclusion: From this study, fungal infections should be included in managing chronic leg ulcers, especially among artisans, famers and gardeners even though there was a significantly higher burden of bacterial infections.展开更多
Background:The age of forest stands is critical information for forest management and conservation,for example for growth modelling,timing of management activities and harvesting,or decisions about protection areas.Ho...Background:The age of forest stands is critical information for forest management and conservation,for example for growth modelling,timing of management activities and harvesting,or decisions about protection areas.However,area-wide information about forest stand age often does not exist.In this study,we developed regression models for large-scale area-wide prediction of age in Norwegian forests.For model development we used more than 4800 plots of the Norwegian National Forest Inventory(NFI)distributed over Norway between latitudes 58°and 65°N in an 18.2 Mha study area.Predictor variables were based on airborne laser scanning(ALS),Sentinel-2,and existing public map data.We performed model validation on an independent data set consisting of 63 spruce stands with known age.Results:The best modelling strategy was to fit independent linear regression models to each observed site index(SI)level and using a SI prediction map in the application of the models.The most important predictor variable was an upper percentile of the ALS heights,and root mean squared errors(RMSEs)ranged between 3 and 31 years(6%to 26%)for SI-specific models,and 21 years(25%)on average.Mean deviance(MD)ranged between^(−1) and 3 years.The models improved with increasing SI and the RMSEs were largest for low SI stands older than 100 years.Using a mapped SI,which is required for practical applications,RMSE and MD on plot level ranged from 19 to 56 years(29%to 53%),and 5 to 37 years(5%to 31%),respectively.For the validation stands,the RMSE and MD were 12(22%)and 2 years(3%),respectively.Conclusions:Tree height estimated from airborne laser scanning and predicted site index were the most important variables in the models describing age.Overall,we obtained good results,especially for stands with high SI.The models could be considered for practical applications,although we see considerable potential for improvements if better SI maps were available.展开更多
Four members of the tandem-pore potassium channel family of Arabidopsis thaliana （TPK1, 2, 3, and 5） reside in the vacuolar membrane, whereas TPK4 is a plasma membrane K^＋-channel. By constructing chimeras between ...Four members of the tandem-pore potassium channel family of Arabidopsis thaliana （TPK1, 2, 3, and 5） reside in the vacuolar membrane, whereas TPK4 is a plasma membrane K^＋-channel. By constructing chimeras between TPK1 and TPK4, we attempted to identify channel domains involved in the trafficking process and found that the TPK1 cytoplasmic C-terminal domain （CT） is critical for the ERas well as Golgi-sorting steps. Following site-directed mutagenesis, we identified a diacidic motif （DLE） required for ER-export of TPK1. However, this diacidic motif in the C-terminus is not conserved among other members of the TPK family, and TPK3 sorting is independent of its CT. Moreover, the 14-3-3 binding site of TPK1, essential for channel activation, is not involved in channel sorting.展开更多
The high-energy/high-intensity laser facility PHELIX of the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt,Germany,has been in operation since 2008.Here,we review the current system performance,which ...The high-energy/high-intensity laser facility PHELIX of the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt,Germany,has been in operation since 2008.Here,we review the current system performance,which is the result of continuous development and further improvement.Through its versatile frontend architecture,PHELIX can be operated in both long-and short-pulse modes,corresponding to ns-pulses with up to 1 kJ pulse energy and sub-ps,200 J pulses,respectively.In the short-pulse mode,the excellent temporal contrast and the control over the wavefront make PHELIX an ideal driver for secondary sources of high-energy ions,neutrons,electrons and X-rays.The long-pulse mode is mainly used for plasma heating,which can then be probed by the heavy-ion beam of the linear accelerator of GSI.In addition,PHELIX can now be used to generate X-rays for studying exotic states of matter created by heavy-ion heating using the ion beam of the heavy-ion synchrotron of GSI.展开更多
Antibacterial adhesives are promising to inhibit biofilms and secondary caries. The objectives of this study were to synthesize and incorporate quaternary ammonium methacrylates into adhesives, and investigate the alk...Antibacterial adhesives are promising to inhibit biofilms and secondary caries. The objectives of this study were to synthesize and incorporate quaternary ammonium methacrylates into adhesives, and investigate the alkyl chain length effects on three-dimensional biofilms adherent on adhesives for the first time. Six quaternary ammonium methacrylates with chain lengths of 3, 6, 9, 12, 16 and 18 were synthesized and incorporated into Scotchbond Multi-Purpose. Streptococcus mutans bacteria were cultured on resin to form biofilms. Confocal laser scanning microscopy was used to measure biofilm thickness, live/dead volumes and live-bacteria percentage vs. distance from resin surface. Biofilm thickness was the greatest for Scotchbond control; it decreased with increasing chain length, reaching a minimum at chain length 16. Live-biofilm volume had a similar trend. Dead-biofilm volume increased with increasing chain length. The adhesive with chain length 9 had 37% live bacteria near resin surface, but close to 100% live bacteria in the biofilm top section. For chain length 16, there were nearly 0% live bacteria throughout the three-dimensional biofilm. In conclusion, strong antibacterial activity was achieved by adding quaternary ammonium into adhesive, with biofilm thickness and live-biofilm volume decreasing as chain length was increased from 3 to 16. Antibacterial adhesives typically only inhibited bacteria close to its surface; however, adhesive with chain length 16 had mostly dead bacteria in the entire three-dimensional biofilm. Antibacterial adhesive with chain length 16 is promising to inhibit biofilms at the margins and combat secondary caries.展开更多
Intracellular Ca2＋ transients are an integral part of the signaling cascade during pathogen-associated molecular pattern （PAMP）-triggered immunity in plants. Yet, our knowledge about the spatial distribution of PAM...Intracellular Ca2＋ transients are an integral part of the signaling cascade during pathogen-associated molecular pattern （PAMP）-triggered immunity in plants. Yet, our knowledge about the spatial distribution of PAMP-induced Ca2＋ signals is limited. Investigation of cell- and tissue-specific properties of Ca2＋- dependent signaling processes requires versatile Ca2＋ reporters that are able to extract spatial information from cellular and subcellular structures, as well as from whole tissues over time periods from seconds to hours. Fluorescence-based reporters cover both a broad spatial and temporal range, which makes them ideally suited to study Ca2＋ signaling in living cells. In this study, we compared two fluorescence-based Ca2＋ sensors： the F6rster resonance energy transfer （FRET）-based reporter yellow cameleon NES-YC3.6 and the intensity-based sensor R-GECO1. We demonstrate that R-GECO1 exhibits a significantly increased signal change compared with ratiometric NES-YC3.6 in response to several stimuli. Due to its superior sensitivity, R-GECO1 is able to report fig22- and chitin-induced Ca2＋ signals on a cellular scale, which allowed identification of defined [Ca2＋]cyt oscillations in epidermal and guard cells in response to the fungal elicitor chitin. Moreover, we discovered that fig22- and chitin-induced Ca2＋ signals in the root initiate from the elongation zone.展开更多
We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heatedwith an intense pulse of heavy ions.In this way,we determine the samples’heatin...We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heatedwith an intense pulse of heavy ions.In this way,we determine the samples’heating dynamics and their microscopic and macroscopic structuralintegrity over a timespan of several microseconds.Connecting the ratio of elastic to inelastic scattering with state-of-the-art density functionaltheory molecular dynamics simulations allows the inference of average temperatures around 1300 K,in agreement with predictions fromstopping power calculations.The simultaneous diffraction measurements show no hints of any volumetric graphitization of the material,butdo indicate the onset of fracture in the diamond sample.Our experiments pave the way for future studies at the Facility for Antiproton andIon Research,where a substantially increased intensity of the heavy ion beam will be available.展开更多
Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older adults.Since direct measurement of VO_(2max)is infeas...Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older adults.Since direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction algorithms.Methods:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)values.We developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging cohorts.Finally,we quantified the associations between measured and predicted VO_(2max)and mortality.Results:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/min.Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,respectively.Incremental quartiles of measured VO_(2max)showed an inverse gradient in mortality risk.Predicted VO_(2max)variables yielded similar effect estimates but were not robust to adjustment.Conclusion:Measured VO_(2max)is a strong predictor of mortality.Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment.Future studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.展开更多
文摘AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.
文摘Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.
文摘Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.
文摘Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P <0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF,P <0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA,which may profoundly influence the development of AAA.
基金This work was supported by the Alexander von Humboldt Foundation(Germany)This research has been in part made possible with the support of the Dutch Province of Limburg(LINK project).PH gratefully acknowledges the Gravitation Program‘Materials-Driven Regeneration’(024.003.013),funded by the Netherlands Organisation for Scientific Research.
文摘Mesoporous bioactive glasses(MBGs)are promising materials for regenerative medicine,due to their favorable properties including bioactivity and degradability.These key properties,but also their surface area,pore structure and pore volume are strongly dependent on synthesis parameters and glass stoichiometry.However,to date no systematic study on MBG properties covering a broad range of possible compositions exists.Here,24 MBG compositions in the SiO_(2)-CaO-P_(2)O_(5) system were synthesized by varying SiO_(2)(60-90 mol%),CaO and P_(2)O_(5) content(both 0 to 40 mol-%),while other synthesis parameters were kept constant.Mesopore characteristics,degradability and bioactivity were analysed.The results showed that,within the tested range of compositions,mesopore formation required a molar SiO_(2) content above 60%but was independent of CaO and P_(2)O_(5) content.While mesopore size did not depend on glass stoichiometry,mesopore arrangement was influenced by the SiO_(2) content.Specific surface area and pore volume were slightly altered by the SiO_(2) content.All materials were degradable;however,degradation as well as bioactivity,i.e.the ability to form a CaP mineral on the surface,depended on stoichiometry.Major differences were found in early surface reactions in simulated body fluid:where some MBGs induced direct hydroxyapatite crystallization,high release of calcium in others resulted in calcite formation.In summary,degradation and bioactivity,both key parameters of MBGs,can be controlled by glass stoichiometry over a broad range while leaving the unique structural parameters of MBGs relatively unaffected.This allows targeted selection of material compositions for specific regenerative medicine applications.
文摘Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and serious complications such as tissue necrosis and osteomyelitis, can result without the timely control of infections. Recent studies have also reported an increase in the association of fungal infections with chronic non-healing ulcers. Aim: To determine the prevalence of bacterial and fungal infections among patients reporting with chronic leg ulcers in participants without co-morbidities. Methods: A prospective cross-sectional study was conducted among patients with chronic leg ulcers at the National Reconstructive Plastic Surgery and Burns Centre, Korle-Bu Teaching Hospital (NRPS/BC-KBTH) and those who consented were enrolled. Characteristics of the wound as well as micro-organisms cultured from wound swabs were recorded. Results: A total of 50 participants were enrolled for the study with the mean (SD) age of 40.7 (10.7) years. Eighty percent of the participants presented with post traumatic leg ulcers with 80% being artisans and traders in the age group 31 - 50 years. There was no statistically significant association between sex and the organism cultured for post traumatic and cellulitis (p-value > 0.05). The prevalence of bacterial and fungal infection was 79.3% and 20.7% respectively. Pseudomonas species was the most isolated bacteria (61.5%) while Aspergillus niger was the most isolated fungi (41%). Conclusion: From this study, fungal infections should be included in managing chronic leg ulcers, especially among artisans, famers and gardeners even though there was a significantly higher burden of bacterial infections.
文摘Background:The age of forest stands is critical information for forest management and conservation,for example for growth modelling,timing of management activities and harvesting,or decisions about protection areas.However,area-wide information about forest stand age often does not exist.In this study,we developed regression models for large-scale area-wide prediction of age in Norwegian forests.For model development we used more than 4800 plots of the Norwegian National Forest Inventory(NFI)distributed over Norway between latitudes 58°and 65°N in an 18.2 Mha study area.Predictor variables were based on airborne laser scanning(ALS),Sentinel-2,and existing public map data.We performed model validation on an independent data set consisting of 63 spruce stands with known age.Results:The best modelling strategy was to fit independent linear regression models to each observed site index(SI)level and using a SI prediction map in the application of the models.The most important predictor variable was an upper percentile of the ALS heights,and root mean squared errors(RMSEs)ranged between 3 and 31 years(6%to 26%)for SI-specific models,and 21 years(25%)on average.Mean deviance(MD)ranged between^(−1) and 3 years.The models improved with increasing SI and the RMSEs were largest for low SI stands older than 100 years.Using a mapped SI,which is required for practical applications,RMSE and MD on plot level ranged from 19 to 56 years(29%to 53%),and 5 to 37 years(5%to 31%),respectively.For the validation stands,the RMSE and MD were 12(22%)and 2 years(3%),respectively.Conclusions:Tree height estimated from airborne laser scanning and predicted site index were the most important variables in the models describing age.Overall,we obtained good results,especially for stands with high SI.The models could be considered for practical applications,although we see considerable potential for improvements if better SI maps were available.
文摘Four members of the tandem-pore potassium channel family of Arabidopsis thaliana （TPK1, 2, 3, and 5） reside in the vacuolar membrane, whereas TPK4 is a plasma membrane K^＋-channel. By constructing chimeras between TPK1 and TPK4, we attempted to identify channel domains involved in the trafficking process and found that the TPK1 cytoplasmic C-terminal domain （CT） is critical for the ERas well as Golgi-sorting steps. Following site-directed mutagenesis, we identified a diacidic motif （DLE） required for ER-export of TPK1. However, this diacidic motif in the C-terminus is not conserved among other members of the TPK family, and TPK3 sorting is independent of its CT. Moreover, the 14-3-3 binding site of TPK1, essential for channel activation, is not involved in channel sorting.
基金funding from the European Union’s Horizon 2020 research and innovation programme via the transnational access and joint research activity programmes of Laserlab(grant agreement Nos.871124 and 654148)funding from the European Union’s HORIZON-INFRA-2022-TECH-01 call under grant agreement number 101095207(THRILL)financed via the BMBF Er UM-APPA collaborative research scheme(contract numbers 05P19RFFA1-Goethe-Universität Frankfurt,05P21RDFA2-Technische Universität Darmstadt,05P19SJFA1 and 05P21SJFA2-Friedrich-Schiller Universität Jena)。
文摘The high-energy/high-intensity laser facility PHELIX of the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt,Germany,has been in operation since 2008.Here,we review the current system performance,which is the result of continuous development and further improvement.Through its versatile frontend architecture,PHELIX can be operated in both long-and short-pulse modes,corresponding to ns-pulses with up to 1 kJ pulse energy and sub-ps,200 J pulses,respectively.In the short-pulse mode,the excellent temporal contrast and the control over the wavefront make PHELIX an ideal driver for secondary sources of high-energy ions,neutrons,electrons and X-rays.The long-pulse mode is mainly used for plasma heating,which can then be probed by the heavy-ion beam of the linear accelerator of GSI.In addition,PHELIX can now be used to generate X-rays for studying exotic states of matter created by heavy-ion heating using the ion beam of the heavy-ion synchrotron of GSI.
基金supported by NIH R01 DE17974West China School of Stomatologya Seed Grant from Department of Endodontics,Prosthodontics and Operative Dentistry,University of Maryland
文摘Antibacterial adhesives are promising to inhibit biofilms and secondary caries. The objectives of this study were to synthesize and incorporate quaternary ammonium methacrylates into adhesives, and investigate the alkyl chain length effects on three-dimensional biofilms adherent on adhesives for the first time. Six quaternary ammonium methacrylates with chain lengths of 3, 6, 9, 12, 16 and 18 were synthesized and incorporated into Scotchbond Multi-Purpose. Streptococcus mutans bacteria were cultured on resin to form biofilms. Confocal laser scanning microscopy was used to measure biofilm thickness, live/dead volumes and live-bacteria percentage vs. distance from resin surface. Biofilm thickness was the greatest for Scotchbond control; it decreased with increasing chain length, reaching a minimum at chain length 16. Live-biofilm volume had a similar trend. Dead-biofilm volume increased with increasing chain length. The adhesive with chain length 9 had 37% live bacteria near resin surface, but close to 100% live bacteria in the biofilm top section. For chain length 16, there were nearly 0% live bacteria throughout the three-dimensional biofilm. In conclusion, strong antibacterial activity was achieved by adding quaternary ammonium into adhesive, with biofilm thickness and live-biofilm volume decreasing as chain length was increased from 3 to 16. Antibacterial adhesives typically only inhibited bacteria close to its surface; however, adhesive with chain length 16 had mostly dead bacteria in the entire three-dimensional biofilm. Antibacterial adhesive with chain length 16 is promising to inhibit biofilms at the margins and combat secondary caries.
文摘Intracellular Ca2＋ transients are an integral part of the signaling cascade during pathogen-associated molecular pattern （PAMP）-triggered immunity in plants. Yet, our knowledge about the spatial distribution of PAMP-induced Ca2＋ signals is limited. Investigation of cell- and tissue-specific properties of Ca2＋- dependent signaling processes requires versatile Ca2＋ reporters that are able to extract spatial information from cellular and subcellular structures, as well as from whole tissues over time periods from seconds to hours. Fluorescence-based reporters cover both a broad spatial and temporal range, which makes them ideally suited to study Ca2＋ signaling in living cells. In this study, we compared two fluorescence-based Ca2＋ sensors： the F6rster resonance energy transfer （FRET）-based reporter yellow cameleon NES-YC3.6 and the intensity-based sensor R-GECO1. We demonstrate that R-GECO1 exhibits a significantly increased signal change compared with ratiometric NES-YC3.6 in response to several stimuli. Due to its superior sensitivity, R-GECO1 is able to report fig22- and chitin-induced Ca2＋ signals on a cellular scale, which allowed identification of defined [Ca2＋]cyt oscillations in epidermal and guard cells in response to the fungal elicitor chitin. Moreover, we discovered that fig22- and chitin-induced Ca2＋ signals in the root initiate from the elongation zone.
基金support by the Federal Ministry of Education and Research(BMBF)under Grant No.05P21RFFA2supported by the Helmholtz Association under Grant No.ERC-RA-0041.
文摘We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heatedwith an intense pulse of heavy ions.In this way,we determine the samples’heating dynamics and their microscopic and macroscopic structuralintegrity over a timespan of several microseconds.Connecting the ratio of elastic to inelastic scattering with state-of-the-art density functionaltheory molecular dynamics simulations allows the inference of average temperatures around 1300 K,in agreement with predictions fromstopping power calculations.The simultaneous diffraction measurements show no hints of any volumetric graphitization of the material,butdo indicate the onset of fracture in the diamond sample.Our experiments pave the way for future studies at the Facility for Antiproton andIon Research,where a substantially increased intensity of the heavy ion beam will be available.
基金supported in part by the Intramural Research Program of the National Institute on Agingsupported by the National Cancer Institute(K01 CA234317)+1 种基金the San Diego State University/UC San Diego Comprehensive Cancer Center Partnership(U54 CA132384 and U54 CA132379)the Alzheimer's Disease Resource Center for Minority Aging Research at the University of California San Diego(P30 AG059299)。
文摘Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older adults.Since direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction algorithms.Methods:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)values.We developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging cohorts.Finally,we quantified the associations between measured and predicted VO_(2max)and mortality.Results:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/min.Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,respectively.Incremental quartiles of measured VO_(2max)showed an inverse gradient in mortality risk.Predicted VO_(2max)variables yielded similar effect estimates but were not robust to adjustment.Conclusion:Measured VO_(2max)is a strong predictor of mortality.Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment.Future studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.
