AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 m...AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.展开更多
Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products r...Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products research is currently undergoing a shift in paradigms.While,for decades,mainly analytical and chemical methods gave access to this group of compounds,nowadays genomics-based methods offer complementary approaches to find,identify and characterize such molecules.This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work.In this context,this review gives a summary of tools and databases that currently are available to mine,identify and characterize natural product biosynthesis pathways and their producers based on‘omics data.A web portal called Secondary Metabolite Bioinformatics Portal(SMBP at http://www.secondarymetabolites.org)is introduced to provide a one-stop catalog and links to these bioinformatics resources.In addition,an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.展开更多
AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveo...AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveolar echinococcosis (AE) drawn from the Echinococcus Databank of the University Hospital of Ulm was reviewed retrospectively. For this reason, CT datasets of combined positron emission tomography (PET)-CT examinations were evaluated. The diagnosis of AE was made in patients with unequivocal seropositivity; positive histological findings following diagnostic puncture or partial resection of the liver; and/or findings typical for AE at either ultrasonography, CT, magnetic resonance imaging or PET-CT. The CT-morphological findings were grouped into the new classification scheme.RESULTS: Within the classification a lesion was dedicated to one out of five “primary morphologies” as well as to one out of six “patterns of calcification”. “primary morphology” and “pattern of calcification” are primarily focussed on separately from each other and combined, whereas the “primary morphology” V is not further characterized by a “pattern of calcification”. Based on the five primary morphologies, further descriptive sub-criteria were appended to types I-III. An analysis of the calcification pattern in relation to the primary morphology revealed the exclusive association of the central calcification with type IV primary morphology. Similarly, certain calcification patterns exhibited a clear predominance for other primary morphologies, which underscores the delimitation of the individual primary morphological types from each other. These relationships in terms of calcification patterns extend into the primary morphological sub-criteria, demonstrating the clear subordination of those criteria.CONCLUSION: The proposed CT-morphological classification (EMUC-CT) is intended to facilitate the recognition and interpretation展开更多
The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） ...The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） and （2） an YSZ （yttria stabilised zirconia） top coat APS （air plasma sprayed） at Forschungszentrum Juelich, Institute of Energy and Climate Research （IEK-2）. The influence of high temperature dwell time, maximum and minimum temperature on crack growth kinetics during thermal cycling of such plasma sprayed TBCs is investigated using scanning electron microscopy and AE （acoustic emission） analysis. Thermocyclic life in terms of accumulated time at maximum temperature decreases with increasing high temperature dwell time and increases with increasing minimum temperature. AE analysis proves that crack growth mainly occurs during cooling at temperatures below the ductile-to-brittle transition temperature of the BC. Superimposed mechanical load cycles accelerate delamination crack growth and, in case of sufficiently high mechanical loadings, result in premature fatigue failure of the substrate. A life prediction model based on TGO growth kinetics and a fracture mechanics approach has been developed which accounts for the influence of maximum and minimum temperature as well as of high temperature dwell time with good accuracy in an extremely wide parameter range.展开更多
AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echin...AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm.Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012.Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters(pre- and post-intervention), medication and surgical treatment(pre- and post-intervention), as well as complications associated with the intervention and patients‘ subsequent clinical courses were analyzed.In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed.RESULTS:Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention.The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years.The most common symptoms were jaundice, abdominal pains, and weight loss.Thenumber of interventions per patient ranged from one to ten.Endoscopic retrograde cholangiopancreatography(ERCP)was most frequently performed in combination with stent placement(82.9%),followed by percutaneous transhepatic cholangiodrainage(31.4%)and ERCP without stent placement(22.9%).In 14.3%of cases,magnetic resonance cholangiopancreatography was performed.A total of eight patients received a biliary stent.A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention.Complications(cholangitis,pancreatitis)oc展开更多
BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead ...BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIM To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODS Consecutively,five experienced examiners evaluated contrast-enhanced abdominal computed tomography(CT)scans for 200 patients with hepatic AE of each of four locations(n=50)in Germany,France and China.Therefore,we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center,performed because of hepatic AE from September 21,2007 to March 21,2018.AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT(EMUC-CT).Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging.Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion.Statistical analysis was performed using SAS Version 9.4(SAS Institute Inc.,Cary,NC,United States).RESULTS Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe(P=0.0091).A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size(P=0.0075).Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe(P<0.0001),and vascular/biliary involvement depended on lesion size.Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations:Vascular/biliary involvem展开更多
The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte conditions.However,recent r...The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte conditions.However,recent research focused on the active state of Mg dissolution,leading to unresolved effects of secondary phases adjacent to a stableα-solid solution passive layer.The present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca alloys.The microstructure was characterized by(transmission-)electron microscopy and synchrotron-based transmission X-ray microscopy.The electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements.A new electrochemical activity sequence(C15>C36>α-Mg>C14)was obtained,as a result of a stable passive layer formation on theα-solid solution.Furthermore,nm-scale Mg-rich precipitates were identified within the Laves phases,which tend to inhibit the corrosion kinetics.展开更多
For a safe and sustainable environment,effective microbes as biocontrol agents are in high demand.We have isolated a new Bacillus velezensis strain DTU001,investigated its antifungal spectrum,sequenced its genome,and ...For a safe and sustainable environment,effective microbes as biocontrol agents are in high demand.We have isolated a new Bacillus velezensis strain DTU001,investigated its antifungal spectrum,sequenced its genome,and uncovered the production of lipopeptides in HPLC-HRMS analysis.To test the antifungal efficacy,extracts of B.velezensis DTU001 was tested against a range of twenty human or plant pathogenic fungi.We demonstrate that inhibitory potential of B.velezensis DTU001 against selected fungi is superior in comparison to single lipopeptide,either iturin or fengycin.The isolate showed analogous biofilm formation to other closely related Bacilli.To further support the biocontrol properties of the isolate,coculture with Candida albicans demonstrated that B.velezensis DTU001 exhibited excellent antiproliferation effect against C.albicans.In summary,the described isolate is a potential antifungal agent with a broad antifungal spectrum that might assist our aims to avoid hazardous pathogenic fungi and provide alternative to toxicity caused by chemicals.展开更多
AIM: To analyze the virtual touch tissue quantification(VTTQ) and virtual touch imaging quantification(VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements.METHODS: One hundred...AIM: To analyze the virtual touch tissue quantification(VTTQ) and virtual touch imaging quantification(VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements.METHODS: One hundred and eighty-six(104 women/82 men) of 323 subjects met the inclusion criteria(age > 18 years, no history of chronic or gastrointestinal disease, body-mass index(BMI) < 30 kg/m2, a fasting period of at least three hours, no history of hepatotoxic pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and normal findings upon ultrasound examination of the abdomen). Measurements were taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner acquired six measurements per position, thereby giving 24 measurements in total.RESULTS: The 95% confidence intervals of mean were1.23-1.29 m/s for VTTQ and 1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and 25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only superficial measurements in the right hepatic lobe with the VTIQ method exhibited an effect of age on shear wave velocity. Measurements acquired using the 6C1 probe with the VTTQ method showed no dependence on BMI. By comparison, BMI influenced measurements taken with the VTIQ method using the 9L4 probe in the superficial and deep areas of the right hepatic lobe, as well as in the left hepatic lobe(P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the right hepatic lobe(P = 0.0001, P = 0.0269). Significant differences were found between measurements with the 6C1(VTTQ) and 9L4 probes(VTIQ)(P = 0.0067), between superficial and deep measurements(P < 0.0001), and between the right and left lobes of the liver(P < 0.0001). CONCLUSION: Measurements in the right lobe and deep regions are preferable. Gender differences must be considered. BMI must be considered when assess展开更多
Globomycin is a cyclic lipodepsipeptide originally isolated from several Streptomyces species which displays strong and selective antibacterial activity against Gram-negative pathogens.Its mode of action is based on t...Globomycin is a cyclic lipodepsipeptide originally isolated from several Streptomyces species which displays strong and selective antibacterial activity against Gram-negative pathogens.Its mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II(LspA),which is absent in eukaryotes and considered an attractive target for the development of new antibiotics.Despite its interesting biological properties,the gene cluster encoding its biosynthesis has not yet been identified.In this study we employed a genome-mining approach in the globomycin-producing Streptomyces sp.CA-278952 to identify a candidate gene cluster responsible for its biosynthesis.A null mutant was constructed using CRISPR base editing where production was abolished,strongly suggesting its involvement in the biosynthesis.The putative gene cluster was then cloned and heterologously expressed in Streptomyces albus J1074 and Streptomyces coelicolor M1146,therefore unambigu-ously linking globomycin and its biosynthetic gene cluster.Our work paves the way for the biosynthesis of new globomycin derivatives with improved pharmacological properties.展开更多
We have investigated twin boundaries in double-lattice hexagonal close-packed metallic materials,focusing on their atomic geometry.Combining accurate ab-initio methods and large-scale atomistic simulations we address ...We have investigated twin boundaries in double-lattice hexagonal close-packed metallic materials,focusing on their atomic geometry.Combining accurate ab-initio methods and large-scale atomistic simulations we address the following two fundamental questions:(i)What are the possible intrinsic twin boundary structures in hcp crystals?(ii)Are these structures stable against small distortions?In order to help end a decade-long controversy over the experimental observations of the atomic structures of twin boundaries,we have determined the energetics,spectra,and transition mechanisms of the twin boundaries.Our results confirm that the mechanical stability controls structures which are observed.展开更多
To the Editor:Alveolar echinococcosis(AE),caused by infection with Echinococcus multilocularis,is regarded as the most dangerous parasitic zoonosis in the temperate climate zones of the northern hemisphere,particularl...To the Editor:Alveolar echinococcosis(AE),caused by infection with Echinococcus multilocularis,is regarded as the most dangerous parasitic zoonosis in the temperate climate zones of the northern hemisphere,particularly across Central Europe and large parts of North-/Central Asia.Left untreated,AE has a very high mortality rate.The liver is the organ most commonly affected showing complex,often infiltrative lesions.When lesions cannot be resected in curative intention,long-term parasitostatic pharmacotherapy with benzimidazoles is indicated to inhibit further extension.[1]展开更多
Atomic force microscopy(AFM)and scanning probe lithography can be used for the mechanical treatment of various surfaces,including polymers,metals,and semiconductors.The technique of nanoshaving,in which materials are ...Atomic force microscopy(AFM)and scanning probe lithography can be used for the mechanical treatment of various surfaces,including polymers,metals,and semiconductors.The technique of nanoshaving,in which materials are removed using the AFM tip,is employed in this work to produce nanopatterns of self-assembled monolayers(SAMs)on two-dimensional(2D)materials.The materials used are monolayers of transition metal dichalcogenides(TMDs),namely,MoS_(2)and WS_(2),which are noncovalently functionalized with perylene diimide(PDI),a perylene derivative.The approach involves rastering an AFM probe across the surface at a controlled increased load in ambient conditions.As a result of the strong bond between PDI SAM and TMD,loads in excess of 1|1N are required to pattern the monolayer.Various predefined patterns,including a grating pattern with feature sizes below 250 nm,are demonstrated.Results indicate the high precision of nanoshaving as an accurate and nondestructive lithographic technique for 2D materials.The work functions of shaved heterostructures are also examined using Kelvin probe force microscopy.展开更多
In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters(BGCs)encoding the biosynthesis of many bioactive compounds,which are the basis for many important drugs used in human med...In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters(BGCs)encoding the biosynthesis of many bioactive compounds,which are the basis for many important drugs used in human medicine.However,the association between BGCs and other functions encoded in the genomes of producers have remained elusive.Here,we present a systems biology workflow that integrates genome mining with a detailed pangenome analysis for detecting genes associated with a particular BGC.We analyzed 3,889 enterobacterial genomes and found 13,266 BGCs,represented by 252 distinct BGC families and 347 additional singletons.A pangenome analysis revealed 88 genes putatively associated with a specific BGC coding for the colon cancer-related colibactin that code for diverse metabolic and regulatory functions.The presented workflow opens up the possibility to discover novel secondary metabolites,better understand their physiological roles,and provides a guide to identify and analyze BGC associated gene sets.展开更多
Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis sp.strain CA-230715 during an antibacterial screening campaign.The structures of these giant mac...Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis sp.strain CA-230715 during an antibacterial screening campaign.The structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their backbones.Genome sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKS clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides A-C.The absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ PKS.In addition,the absolute stereochemistry of gargantulide A has now been revised and completed.Gargantulides B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii.展开更多
CRISPR/Cas9 systems are an established tool in genome engineering.As double strand breaks caused by the standard Cas9-based knock-out techniques can be problematic in some organisms,new systems were developed that can...CRISPR/Cas9 systems are an established tool in genome engineering.As double strand breaks caused by the standard Cas9-based knock-out techniques can be problematic in some organisms,new systems were developed that can efficiently create knock-outs without causing double strand breaks to elegantly sidestep these issues.The recently published CRISPR-BEST base editor system for actinobacteria is built around a C to T or A to G base exchange.These base editing systems however require additional constraints to be considered for designing the sgRNAs.Here,we present an updated version of the interactive CRISPy-web single guide RNA design tool https://crispy.secondarymetabolites.org/that was built to support“classical”CRISPR and now also CRISPRBEST workflows.展开更多
文摘AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.
文摘Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products research is currently undergoing a shift in paradigms.While,for decades,mainly analytical and chemical methods gave access to this group of compounds,nowadays genomics-based methods offer complementary approaches to find,identify and characterize such molecules.This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work.In this context,this review gives a summary of tools and databases that currently are available to mine,identify and characterize natural product biosynthesis pathways and their producers based on‘omics data.A web portal called Secondary Metabolite Bioinformatics Portal(SMBP at http://www.secondarymetabolites.org)is introduced to provide a one-stop catalog and links to these bioinformatics resources.In addition,an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.
文摘AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveolar echinococcosis (AE) drawn from the Echinococcus Databank of the University Hospital of Ulm was reviewed retrospectively. For this reason, CT datasets of combined positron emission tomography (PET)-CT examinations were evaluated. The diagnosis of AE was made in patients with unequivocal seropositivity; positive histological findings following diagnostic puncture or partial resection of the liver; and/or findings typical for AE at either ultrasonography, CT, magnetic resonance imaging or PET-CT. The CT-morphological findings were grouped into the new classification scheme.RESULTS: Within the classification a lesion was dedicated to one out of five “primary morphologies” as well as to one out of six “patterns of calcification”. “primary morphology” and “pattern of calcification” are primarily focussed on separately from each other and combined, whereas the “primary morphology” V is not further characterized by a “pattern of calcification”. Based on the five primary morphologies, further descriptive sub-criteria were appended to types I-III. An analysis of the calcification pattern in relation to the primary morphology revealed the exclusive association of the central calcification with type IV primary morphology. Similarly, certain calcification patterns exhibited a clear predominance for other primary morphologies, which underscores the delimitation of the individual primary morphological types from each other. These relationships in terms of calcification patterns extend into the primary morphological sub-criteria, demonstrating the clear subordination of those criteria.CONCLUSION: The proposed CT-morphological classification (EMUC-CT) is intended to facilitate the recognition and interpretation
文摘The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） and （2） an YSZ （yttria stabilised zirconia） top coat APS （air plasma sprayed） at Forschungszentrum Juelich, Institute of Energy and Climate Research （IEK-2）. The influence of high temperature dwell time, maximum and minimum temperature on crack growth kinetics during thermal cycling of such plasma sprayed TBCs is investigated using scanning electron microscopy and AE （acoustic emission） analysis. Thermocyclic life in terms of accumulated time at maximum temperature decreases with increasing high temperature dwell time and increases with increasing minimum temperature. AE analysis proves that crack growth mainly occurs during cooling at temperatures below the ductile-to-brittle transition temperature of the BC. Superimposed mechanical load cycles accelerate delamination crack growth and, in case of sufficiently high mechanical loadings, result in premature fatigue failure of the substrate. A life prediction model based on TGO growth kinetics and a fracture mechanics approach has been developed which accounts for the influence of maximum and minimum temperature as well as of high temperature dwell time with good accuracy in an extremely wide parameter range.
文摘AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm.Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012.Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters(pre- and post-intervention), medication and surgical treatment(pre- and post-intervention), as well as complications associated with the intervention and patients‘ subsequent clinical courses were analyzed.In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed.RESULTS:Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention.The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years.The most common symptoms were jaundice, abdominal pains, and weight loss.Thenumber of interventions per patient ranged from one to ten.Endoscopic retrograde cholangiopancreatography(ERCP)was most frequently performed in combination with stent placement(82.9%),followed by percutaneous transhepatic cholangiodrainage(31.4%)and ERCP without stent placement(22.9%).In 14.3%of cases,magnetic resonance cholangiopancreatography was performed.A total of eight patients received a biliary stent.A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention.Complications(cholangitis,pancreatitis)oc
基金Supported by a German Research Foundation funded project called“Establishment of a national database for alveolar echinococcosis”,No.KA 4356/3-1“Implementation of interfaces for the standardization of nationaldatabase systems for alveolar echinococcosis and its transformation processes”,No.KR 5204/1-2+1 种基金Multiple imaging study of the Hepatic Alveolar Echinococcosis after albendazole treatment,the Qinghai Science and Technology Department,No.2017-SF-158and the Müller Holding Ltd.and Co.KG Ulm.
文摘BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIM To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODS Consecutively,five experienced examiners evaluated contrast-enhanced abdominal computed tomography(CT)scans for 200 patients with hepatic AE of each of four locations(n=50)in Germany,France and China.Therefore,we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center,performed because of hepatic AE from September 21,2007 to March 21,2018.AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT(EMUC-CT).Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging.Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion.Statistical analysis was performed using SAS Version 9.4(SAS Institute Inc.,Cary,NC,United States).RESULTS Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe(P=0.0091).A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size(P=0.0075).Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe(P<0.0001),and vascular/biliary involvement depended on lesion size.Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations:Vascular/biliary involvem
基金the financial support of the Deutsche Forschungsgemeinschaft(DFG)of the Collaborative Research Center(CRC)1394“Structural and Chemical Atomic Complexity-from defect phase diagrams to material properties”–project ID 409476157the Excellence Strategy of the Federal Government and the L?nder project IDG:(DE-82)EXS-SF-OPSF596。
文摘The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte conditions.However,recent research focused on the active state of Mg dissolution,leading to unresolved effects of secondary phases adjacent to a stableα-solid solution passive layer.The present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca alloys.The microstructure was characterized by(transmission-)electron microscopy and synchrotron-based transmission X-ray microscopy.The electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements.A new electrochemical activity sequence(C15>C36>α-Mg>C14)was obtained,as a result of a stable passive layer formation on theα-solid solution.Furthermore,nm-scale Mg-rich precipitates were identified within the Laves phases,which tend to inhibit the corrosion kinetics.
基金This work was supported by the Danish National Research Foundation(DNRF137)for the Center for Microbial Secondary Metabolites(CeMiSt)SD was supported by a Novozymes and Henning Holck Larsen fellowship during her stay at DTU.TW was supported by a grant from Novo Nordisk Foundation(NNF10CC1016517).
文摘For a safe and sustainable environment,effective microbes as biocontrol agents are in high demand.We have isolated a new Bacillus velezensis strain DTU001,investigated its antifungal spectrum,sequenced its genome,and uncovered the production of lipopeptides in HPLC-HRMS analysis.To test the antifungal efficacy,extracts of B.velezensis DTU001 was tested against a range of twenty human or plant pathogenic fungi.We demonstrate that inhibitory potential of B.velezensis DTU001 against selected fungi is superior in comparison to single lipopeptide,either iturin or fengycin.The isolate showed analogous biofilm formation to other closely related Bacilli.To further support the biocontrol properties of the isolate,coculture with Candida albicans demonstrated that B.velezensis DTU001 exhibited excellent antiproliferation effect against C.albicans.In summary,the described isolate is a potential antifungal agent with a broad antifungal spectrum that might assist our aims to avoid hazardous pathogenic fungi and provide alternative to toxicity caused by chemicals.
文摘AIM: To analyze the virtual touch tissue quantification(VTTQ) and virtual touch imaging quantification(VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements.METHODS: One hundred and eighty-six(104 women/82 men) of 323 subjects met the inclusion criteria(age > 18 years, no history of chronic or gastrointestinal disease, body-mass index(BMI) < 30 kg/m2, a fasting period of at least three hours, no history of hepatotoxic pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and normal findings upon ultrasound examination of the abdomen). Measurements were taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner acquired six measurements per position, thereby giving 24 measurements in total.RESULTS: The 95% confidence intervals of mean were1.23-1.29 m/s for VTTQ and 1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and 25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only superficial measurements in the right hepatic lobe with the VTIQ method exhibited an effect of age on shear wave velocity. Measurements acquired using the 6C1 probe with the VTTQ method showed no dependence on BMI. By comparison, BMI influenced measurements taken with the VTIQ method using the 9L4 probe in the superficial and deep areas of the right hepatic lobe, as well as in the left hepatic lobe(P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the right hepatic lobe(P = 0.0001, P = 0.0269). Significant differences were found between measurements with the 6C1(VTTQ) and 9L4 probes(VTIQ)(P = 0.0067), between superficial and deep measurements(P < 0.0001), and between the right and left lobes of the liver(P < 0.0001). CONCLUSION: Measurements in the right lobe and deep regions are preferable. Gender differences must be considered. BMI must be considered when assess
基金funded by grants of the Novo Nordisk Foundation,Denmark(NNF16OC0021746 to O.G.,T.W.,NNF20CC0035580 to T.W.).
文摘Globomycin is a cyclic lipodepsipeptide originally isolated from several Streptomyces species which displays strong and selective antibacterial activity against Gram-negative pathogens.Its mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II(LspA),which is absent in eukaryotes and considered an attractive target for the development of new antibiotics.Despite its interesting biological properties,the gene cluster encoding its biosynthesis has not yet been identified.In this study we employed a genome-mining approach in the globomycin-producing Streptomyces sp.CA-278952 to identify a candidate gene cluster responsible for its biosynthesis.A null mutant was constructed using CRISPR base editing where production was abolished,strongly suggesting its involvement in the biosynthesis.The putative gene cluster was then cloned and heterologously expressed in Streptomyces albus J1074 and Streptomyces coelicolor M1146,therefore unambigu-ously linking globomycin and its biosynthetic gene cluster.Our work paves the way for the biosynthesis of new globomycin derivatives with improved pharmacological properties.
基金the financial supports of the Max-Planck Society at the Max-Planck-Institut fur Eisenforschung GmbH.the support from the Academy of Sciences of the Czech Republic through the Fellowship of J.E.Purkyne.
文摘We have investigated twin boundaries in double-lattice hexagonal close-packed metallic materials,focusing on their atomic geometry.Combining accurate ab-initio methods and large-scale atomistic simulations we address the following two fundamental questions:(i)What are the possible intrinsic twin boundary structures in hcp crystals?(ii)Are these structures stable against small distortions?In order to help end a decade-long controversy over the experimental observations of the atomic structures of twin boundaries,we have determined the energetics,spectra,and transition mechanisms of the twin boundaries.Our results confirm that the mechanical stability controls structures which are observed.
基金The results included data from a German Research Foundation(DFG)funded project called“Establishment of a national database for alveolar echinococcosis”(Ref.No.KA 4356/3-1)“Implementation of interfaces to unify national database systems for alveolar echinococcosis and its transformation processes”(Ref.No.KR 5204/1-2).
文摘To the Editor:Alveolar echinococcosis(AE),caused by infection with Echinococcus multilocularis,is regarded as the most dangerous parasitic zoonosis in the temperate climate zones of the northern hemisphere,particularly across Central Europe and large parts of North-/Central Asia.Left untreated,AE has a very high mortality rate.The liver is the organ most commonly affected showing complex,often infiltrative lesions.When lesions cannot be resected in curative intention,long-term parasitostatic pharmacotherapy with benzimidazoles is indicated to inhibit further extension.[1]
基金Science Foundation Ireland,PI_15/IA/3131,Georg Stefan Duesberg。
文摘Atomic force microscopy(AFM)and scanning probe lithography can be used for the mechanical treatment of various surfaces,including polymers,metals,and semiconductors.The technique of nanoshaving,in which materials are removed using the AFM tip,is employed in this work to produce nanopatterns of self-assembled monolayers(SAMs)on two-dimensional(2D)materials.The materials used are monolayers of transition metal dichalcogenides(TMDs),namely,MoS_(2)and WS_(2),which are noncovalently functionalized with perylene diimide(PDI),a perylene derivative.The approach involves rastering an AFM probe across the surface at a controlled increased load in ambient conditions.As a result of the strong bond between PDI SAM and TMD,loads in excess of 1|1N are required to pattern the monolayer.Various predefined patterns,including a grating pattern with feature sizes below 250 nm,are demonstrated.Results indicate the high precision of nanoshaving as an accurate and nondestructive lithographic technique for 2D materials.The work functions of shaved heterostructures are also examined using Kelvin probe force microscopy.
基金supported by the Leopold Franzens Universitatthe Austrian Science Fund(FWF)+4 种基金the Austrian Research Promotion Agency(FFG)(ViennaAustria)the European Defence Agency(EDA) via a Joint Investment Programme on Force Protection(JIP-FP)projectthe European Commission(BrusselsBelgium)
基金supported by grants from the Novo Nordisk Foundation(NNF20CC0035580,NNF16OC0021746)。
文摘In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters(BGCs)encoding the biosynthesis of many bioactive compounds,which are the basis for many important drugs used in human medicine.However,the association between BGCs and other functions encoded in the genomes of producers have remained elusive.Here,we present a systems biology workflow that integrates genome mining with a detailed pangenome analysis for detecting genes associated with a particular BGC.We analyzed 3,889 enterobacterial genomes and found 13,266 BGCs,represented by 252 distinct BGC families and 347 additional singletons.A pangenome analysis revealed 88 genes putatively associated with a specific BGC coding for the colon cancer-related colibactin that code for diverse metabolic and regulatory functions.The presented workflow opens up the possibility to discover novel secondary metabolites,better understand their physiological roles,and provides a guide to identify and analyze BGC associated gene sets.
基金funded by grants of the Novo Nordisk Foundation,Denmark[NNF20CC0035580,NNF16OC0021746]Doctoral Programme in Pharmacy(B15.56.1),Doctoral School in Health Sciences,University of Granada,52005 Granada,Spain.
文摘Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis sp.strain CA-230715 during an antibacterial screening campaign.The structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their backbones.Genome sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKS clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides A-C.The absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ PKS.In addition,the absolute stereochemistry of gargantulide A has now been revised and completed.Gargantulides B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii.
基金This work was supported by grants from the Novo Nordisk Foundation[NNF10CC1016517,NNF15OC0016226,NNF16OC0021746].
文摘CRISPR/Cas9 systems are an established tool in genome engineering.As double strand breaks caused by the standard Cas9-based knock-out techniques can be problematic in some organisms,new systems were developed that can efficiently create knock-outs without causing double strand breaks to elegantly sidestep these issues.The recently published CRISPR-BEST base editor system for actinobacteria is built around a C to T or A to G base exchange.These base editing systems however require additional constraints to be considered for designing the sgRNAs.Here,we present an updated version of the interactive CRISPy-web single guide RNA design tool https://crispy.secondarymetabolites.org/that was built to support“classical”CRISPR and now also CRISPRBEST workflows.
