The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are ...The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are am- plified in several cascades by a combination of reductases, oxygenases, and transferases to result in an organ and devel- opmentally specific pattern of metabolites, characteristic for each plant species. During the last decade, methodology driven targeted and non-targeted approaches in several plant species have enabled the identification of the participating enzymes of this complex biosynthetic machinery, and revealed numerous genes, enzymes, and metabolites essential for regulation and compartmentation. Considerable success in structural and computational biology, combined with the an- alytical sensitivity to detect even trace compounds and smallest changes in the metabolite, transcript, or enzyme pattern, has facilitated progress towards a comprehensive view of the plant response to its biotic and abiotic environment. Trans- genic approaches have been used to reveal insights into an apparently redundant gene and enzyme pattern required for functional integrity and plasticity of the various phenylpropanoid biosynthetic pathways. Nevertheless, the function and impact of all members of a gene family remain to be completely established. This review aims to give an update on the various facets of the general phenylpropanoid pathway, which is not only restricted to common lignin or flavonoid biosynthesis, but feeds into a variety of other aromatic metabolites like coumarins, phenolic volatiles, or hydrolyzable tannins.展开更多
AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in...AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this study.All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixtyeight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%); P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.展开更多
Many measurements of B decays involve admixtures of B hadrons. Previously we arbitrarily included such admixtures in the B±section, but because of their importance we have created two new sections：
The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 papers, we list, evaluate, and average measured properties of gauge bosons and the ...The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on： Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews （and errata） are also available on the Particle Data Group website： http ：//pdg. lbl. gov.展开更多
AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meanin...AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.展开更多
AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol (L/M)...AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.RESULTS: Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.展开更多
The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin(Hb A1c). Despite its importance as an indicator for the development of diabeticcomplications...The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin(Hb A1c). Despite its importance as an indicator for the development of diabeticcomplications, recent studies have revealed that this metric has some limitations; it conveys a rather complex message, which has to be taken into consideration for diabetes screening and treatment. On the basis of recent clinical trials, the relationship between Hb A1 c and cardiovascular outcomes in long-standing diabetes has been called into question. It becomes obvious that other surrogate and biomarkers are needed to better predict cardiovascular diabetes complications and assess efficiency of therapy. Glycated albumin, fructosamin, and 1,5-anhydroglucitol have received growing interest as alternative markers of glycemic control. In addition to measures of hyperglycemia, advanced glucose monitoring methods became available. An indispensible adjunct to Hb A1 c in routine diabetes care is selfmonitoring of blood glucose. This monitoring method is now widely used, as it provides immediate feedback to patients on short-term changes, involving fasting, preprandial, and postprandial glucose levels. Beyond the traditional metrics, glycemic variability has been identified as a predictor of hypoglycemia, and it might also be implicated in the pathogenesis of vascular diabetes complications. Assessment of glycemic variability is thus important, but exact quantification requires frequently sampled glucose measurements. In order to optimize diabetes treatment, there is a need for both key metrics of glycemic control on a day-to-day basis and for more advanced, user-friendly monitoring methods. In addition to traditional discontinuous glucose testing, continuous glucose sensing has become a useful tool to reveal insufficient glycemic management. This new technology is particularly effective in patients with complicated diabetes and provides the opportunity to characterize glucose dynamics. Several continuous glucose moni展开更多
The steady progress in medical diagnosis and treatment of diseases largely hinges on the steady development and improvement of modern imaging modalities.Raman spectroscopy has attracted increasing attention for clinic...The steady progress in medical diagnosis and treatment of diseases largely hinges on the steady development and improvement of modern imaging modalities.Raman spectroscopy has attracted increasing attention for clinical applications as it is label-free,non-invasive,and delivers molecular fingerprinting information of a sample.In combination with fiber optic probes,it also allows easy access to different body parts of a patient.However,image acquisition with fiber optic probes is currently not possible.Here,we introduce a fiber optic probe-based Raman imaging system for the real-time molecular virtual reality data visualization of chemical boundaries on a computer screen and the physical world.The approach is developed around a computer vision-based positional tracking system in conjunction with photometric stereo and augmented and mixed chemical reality,enabling molecular imaging and direct visualization of molecular boundaries of three-dimensional surfaces.The proposed approach achieves a spatial resolution of 0.5 mm in the transverse plane and a topology resolution of 0.6 mm,with a spectral sampling frequency of 10 Hz,and can be used to image large tissue areas in a few minutes,making it highly suitable for clinical tissueboundary demarcation.A variety of applications on biological samples,i.e.,distribution of pharmaceutical compounds,brain-tumor phantom,and various types of sarcoma have been characterized,showing that the system enables rapid and intuitive assessment of molecular boundaries.展开更多
A growing body of studies and systematic reviews show evidence of the beneficial effects of physical exercise on core symptoms of ADHD. Furthermore, studies indicate that physical exercise as an adjuvant can enhance t...A growing body of studies and systematic reviews show evidence of the beneficial effects of physical exercise on core symptoms of ADHD. Furthermore, studies indicate that physical exercise as an adjuvant can enhance the effects of medication in the treatment of ADHD. Aerobic and coordinative exercises improve executive functioning through their effect on neurocognitive domains that are implicated in ADHD. It is postulated that through their specific modus operandi, aerobic exercise, by raising cortical arousal levels, improves impaired alerting functions whereas coordinative exercises improve the regulation of inhibitory control through the involvement of a higher variety of frontal-dependent cognitive processes. The increasing use of routine neurocognitive testing with continuous performance tests (CPT), such as the QbTest, at clinical assessments for ADHD allows for an innovative approach to identify the assessment impairments in alerting function and inhibition control that are related to ADHD and accordingly choose aerobic or coordinative physical exercise in a more targeted fashion.展开更多
Lipoxygenase(LOX)is an important contributor to the formation of aroma-active C6 aldehydes in apple(Malus×domestica)fruit upon tissue disruption but little is known about its role in autonomously produced aroma v...Lipoxygenase(LOX)is an important contributor to the formation of aroma-active C6 aldehydes in apple(Malus×domestica)fruit upon tissue disruption but little is known about its role in autonomously produced aroma volatiles from intact tissue.We explored the expression of 22 putative LOX genes in apple throughout ripening,but only six LOXs were expressed in a ripening-dependent manner.Recombinant LOX1:Md:1a,LOX1:Md:1c,LOX2:Md:2a and LOX2:Md:2b proteins showed 13/9-LOX,9-LOX,13/9-LOX and 13-LOX activity with linoleic acid,respectively.While products of LOX1:Md:1c and LOX2:Md:2b were S-configured,LOX1:Md:1a and LOX2:Md:2a formed 13(R)-hydroperoxides as major products.Site-directed mutagenesis of Gly567 to an alanine converted the dual positional specific LOX1:Md:1a to an enzyme with a high specificity for 9(S)-hydroperoxide formation.The high expression level of the corresponding MdLOX1a gene in stored apple fruit,the genetic association with a quantitative trait locus for fruit ester and the remarkable agreement in regio-and stereoselectivity of the LOX1:Md:1a reaction with the overall LOX activity found in mature apple fruits,suggest a major physiological function of LOX1:Md:1a during climacteric ripening of apples.While LOX1:Md:1c,LOX2:Md:2a and LOX2:Md:2b may contribute to aldehyde production in immature fruit upon cell disruption our results furnish additional evidence that LOX1:Md:1a probably regulates the availability of precursors for ester production in intact fruit tissue.展开更多
Microbial electrochemical technologies have been extensively employed for phenol removal.Yet,previous research has yielded inconsistent results,leaving uncertainties regarding the feasibility of phenol degradation und...Microbial electrochemical technologies have been extensively employed for phenol removal.Yet,previous research has yielded inconsistent results,leaving uncertainties regarding the feasibility of phenol degradation under strictly anaerobic conditions using anodes as sole terminal electron acceptors.In this study,we employed high-performance liquid chromatography and gas chromatography-mass spectrometry to investigate the anaerobic phenol degradation pathway.Our findings provide robust evidence for the purely anaerobic degradation of phenol,as we identified benzoic acid,4-hydroxybenzoic acid,glutaric acid,and other metabolites of this pathway.Notably,no typical intermediates of the aerobic phenol degradation pathway were detected.One-chamber reactors(t0.4 V vs.SHE)exhibited a phenol removal rate of 3.5±0.2 mg L^(-1) d^(-1),while two-chamber reactors showed 3.6±0.1 and 2.6±0.9 mg L^(-1) d^(-1) at anode potentials of t0.4 and t 0.2 V,respectively.Our results also suggest that the reactor configuration certainly influenced the microbial community,presumably leading to different ratios of phenol consumers and microorganisms feeding on degradation products.展开更多
The increasing share of renewable energy in the electricity grid and progressing changes in power consumption have led to fluctuating,and weather-dependent power flows.To ensure grid stability,grid operators rely on p...The increasing share of renewable energy in the electricity grid and progressing changes in power consumption have led to fluctuating,and weather-dependent power flows.To ensure grid stability,grid operators rely on power forecasts which are crucial for grid calculations and planning.In this paper,a Multi-Task Learning approach is combined with a Graph Neural Network(GNN)to predict vertical power flows at transformers connecting high and extra-high voltage levels.The proposed method accounts for local differences in power flow characteristics by using an Embedding Multi-Task Learning approach.The use of a Bayesian embedding to capture the latent node characteristics allows to share the weights across all transformers in the subsequent node-invariant GNN while still allowing the individual behavioral patterns of the transformers to be distinguished.At the same time,dependencies between transformers are considered by the GNN architecture which can learn relationships between different transformers and thus take into account that power flows in an electricity network are not independent from each other.The effectiveness of the proposed method is demonstrated through evaluation on two real-world data sets provided by two of four German Transmission System Operators,comprising large portions of the operated German transmission grid.The results show that the proposed Multi-Task Graph Neural Network is a suitable representation learner for electricity networks with a clear advantage provided by the preceding embedding layer.It is able to capture interconnections between correlated transformers and indeed improves the performance in power flow prediction compared to standard Neural Networks.A sign test shows that the proposed model reduces the test RMSE on both data sets compared to the benchmark models significantly.展开更多
Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing c...Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.展开更多
At the sediment-water interfaces,filamentous cable bacteria transport electrons from sulfide oxidation along their filaments towards oxygen or nitrate as electron acceptors.These multicellular bacteria belonging to th...At the sediment-water interfaces,filamentous cable bacteria transport electrons from sulfide oxidation along their filaments towards oxygen or nitrate as electron acceptors.These multicellular bacteria belonging to the family Desulfobulbaceae thus form a biogeobattery that mediates redox processes between multiple elements.Cable bacteria were first reported in 2012.In the past years,cable bacteria have been found to be widely distributed across the globe.Their potential in shaping the surface water environments has been extensively studied but is not fully elucidated.In this review,the biogeochemical characteristics,conduction mechanisms,and geographical distribution of cable bacteria,as well as their ecological effects,are systematically reviewed and discussed.Novel insights for understanding and applying the role of cable bacteria in aquatic ecology are summarized.展开更多
文摘The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are am- plified in several cascades by a combination of reductases, oxygenases, and transferases to result in an organ and devel- opmentally specific pattern of metabolites, characteristic for each plant species. During the last decade, methodology driven targeted and non-targeted approaches in several plant species have enabled the identification of the participating enzymes of this complex biosynthetic machinery, and revealed numerous genes, enzymes, and metabolites essential for regulation and compartmentation. Considerable success in structural and computational biology, combined with the an- alytical sensitivity to detect even trace compounds and smallest changes in the metabolite, transcript, or enzyme pattern, has facilitated progress towards a comprehensive view of the plant response to its biotic and abiotic environment. Trans- genic approaches have been used to reveal insights into an apparently redundant gene and enzyme pattern required for functional integrity and plasticity of the various phenylpropanoid biosynthetic pathways. Nevertheless, the function and impact of all members of a gene family remain to be completely established. This review aims to give an update on the various facets of the general phenylpropanoid pathway, which is not only restricted to common lignin or flavonoid biosynthesis, but feeds into a variety of other aromatic metabolites like coumarins, phenolic volatiles, or hydrolyzable tannins.
文摘AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this study.All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixtyeight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%); P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.
文摘Many measurements of B decays involve admixtures of B hadrons. Previously we arbitrarily included such admixtures in the B±section, but because of their importance we have created two new sections：
基金supported by the Director,Office of Science,Office of High Energy Physics of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231the U.S.National Science Foundation under Agreement No.PHY-0652989+3 种基金the European Laboratory for Particle Physics(CERN)an implementing arrangement between the governments of Japan(MEXT:Ministry of Education,Culture,Sports,Science and Technology)and the United States(DOE)on cooperative research and developmentthe Italian National Institute of Nuclear Physics(INFN)B.C.F.was supported by the U.S.National Science Foundation Grant PHY-1214082
文摘The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on： Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews （and errata） are also available on the Particle Data Group website： http ：//pdg. lbl. gov.
基金Supported by the Gennan Research Society (DFG-SFB 585/A8) and the Dr. Heinz Maurer Grant KFB 1.7
文摘AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.
基金Supported by the Federal Ministry of Education and Research(BMBF)Germany(FKZ:01 E0 1002)(in part)
文摘AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.RESULTS: Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.
文摘The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin(Hb A1c). Despite its importance as an indicator for the development of diabeticcomplications, recent studies have revealed that this metric has some limitations; it conveys a rather complex message, which has to be taken into consideration for diabetes screening and treatment. On the basis of recent clinical trials, the relationship between Hb A1 c and cardiovascular outcomes in long-standing diabetes has been called into question. It becomes obvious that other surrogate and biomarkers are needed to better predict cardiovascular diabetes complications and assess efficiency of therapy. Glycated albumin, fructosamin, and 1,5-anhydroglucitol have received growing interest as alternative markers of glycemic control. In addition to measures of hyperglycemia, advanced glucose monitoring methods became available. An indispensible adjunct to Hb A1 c in routine diabetes care is selfmonitoring of blood glucose. This monitoring method is now widely used, as it provides immediate feedback to patients on short-term changes, involving fasting, preprandial, and postprandial glucose levels. Beyond the traditional metrics, glycemic variability has been identified as a predictor of hypoglycemia, and it might also be implicated in the pathogenesis of vascular diabetes complications. Assessment of glycemic variability is thus important, but exact quantification requires frequently sampled glucose measurements. In order to optimize diabetes treatment, there is a need for both key metrics of glycemic control on a day-to-day basis and for more advanced, user-friendly monitoring methods. In addition to traditional discontinuous glucose testing, continuous glucose sensing has become a useful tool to reveal insufficient glycemic management. This new technology is particularly effective in patients with complicated diabetes and provides the opportunity to characterize glucose dynamics. Several continuous glucose moni
基金funded by the ERA-CVD project MultiFib(01KL1904)support from the China Scholarship Council.
文摘The steady progress in medical diagnosis and treatment of diseases largely hinges on the steady development and improvement of modern imaging modalities.Raman spectroscopy has attracted increasing attention for clinical applications as it is label-free,non-invasive,and delivers molecular fingerprinting information of a sample.In combination with fiber optic probes,it also allows easy access to different body parts of a patient.However,image acquisition with fiber optic probes is currently not possible.Here,we introduce a fiber optic probe-based Raman imaging system for the real-time molecular virtual reality data visualization of chemical boundaries on a computer screen and the physical world.The approach is developed around a computer vision-based positional tracking system in conjunction with photometric stereo and augmented and mixed chemical reality,enabling molecular imaging and direct visualization of molecular boundaries of three-dimensional surfaces.The proposed approach achieves a spatial resolution of 0.5 mm in the transverse plane and a topology resolution of 0.6 mm,with a spectral sampling frequency of 10 Hz,and can be used to image large tissue areas in a few minutes,making it highly suitable for clinical tissueboundary demarcation.A variety of applications on biological samples,i.e.,distribution of pharmaceutical compounds,brain-tumor phantom,and various types of sarcoma have been characterized,showing that the system enables rapid and intuitive assessment of molecular boundaries.
文摘A growing body of studies and systematic reviews show evidence of the beneficial effects of physical exercise on core symptoms of ADHD. Furthermore, studies indicate that physical exercise as an adjuvant can enhance the effects of medication in the treatment of ADHD. Aerobic and coordinative exercises improve executive functioning through their effect on neurocognitive domains that are implicated in ADHD. It is postulated that through their specific modus operandi, aerobic exercise, by raising cortical arousal levels, improves impaired alerting functions whereas coordinative exercises improve the regulation of inhibitory control through the involvement of a higher variety of frontal-dependent cognitive processes. The increasing use of routine neurocognitive testing with continuous performance tests (CPT), such as the QbTest, at clinical assessments for ADHD allows for an innovative approach to identify the assessment impairments in alerting function and inhibition control that are related to ADHD and accordingly choose aerobic or coordinative physical exercise in a more targeted fashion.
基金This research was financially supported by the Deutsche Forschungsgemeinschaft in frame of the project numbers AOBJ 575560 and AOBJ 575561.
文摘Lipoxygenase(LOX)is an important contributor to the formation of aroma-active C6 aldehydes in apple(Malus×domestica)fruit upon tissue disruption but little is known about its role in autonomously produced aroma volatiles from intact tissue.We explored the expression of 22 putative LOX genes in apple throughout ripening,but only six LOXs were expressed in a ripening-dependent manner.Recombinant LOX1:Md:1a,LOX1:Md:1c,LOX2:Md:2a and LOX2:Md:2b proteins showed 13/9-LOX,9-LOX,13/9-LOX and 13-LOX activity with linoleic acid,respectively.While products of LOX1:Md:1c and LOX2:Md:2b were S-configured,LOX1:Md:1a and LOX2:Md:2a formed 13(R)-hydroperoxides as major products.Site-directed mutagenesis of Gly567 to an alanine converted the dual positional specific LOX1:Md:1a to an enzyme with a high specificity for 9(S)-hydroperoxide formation.The high expression level of the corresponding MdLOX1a gene in stored apple fruit,the genetic association with a quantitative trait locus for fruit ester and the remarkable agreement in regio-and stereoselectivity of the LOX1:Md:1a reaction with the overall LOX activity found in mature apple fruits,suggest a major physiological function of LOX1:Md:1a during climacteric ripening of apples.While LOX1:Md:1c,LOX2:Md:2a and LOX2:Md:2b may contribute to aldehyde production in immature fruit upon cell disruption our results furnish additional evidence that LOX1:Md:1a probably regulates the availability of precursors for ester production in intact fruit tissue.
基金China Scholarship Council(CSC201804910500)for 4-year granting study abroadsupported by the Helmholtz Association in the frame of the Integration Platform“Tapping nature's potential for sustainable production and a healthy environment”at the UFZ.
文摘Microbial electrochemical technologies have been extensively employed for phenol removal.Yet,previous research has yielded inconsistent results,leaving uncertainties regarding the feasibility of phenol degradation under strictly anaerobic conditions using anodes as sole terminal electron acceptors.In this study,we employed high-performance liquid chromatography and gas chromatography-mass spectrometry to investigate the anaerobic phenol degradation pathway.Our findings provide robust evidence for the purely anaerobic degradation of phenol,as we identified benzoic acid,4-hydroxybenzoic acid,glutaric acid,and other metabolites of this pathway.Notably,no typical intermediates of the aerobic phenol degradation pathway were detected.One-chamber reactors(t0.4 V vs.SHE)exhibited a phenol removal rate of 3.5±0.2 mg L^(-1) d^(-1),while two-chamber reactors showed 3.6±0.1 and 2.6±0.9 mg L^(-1) d^(-1) at anode potentials of t0.4 and t 0.2 V,respectively.Our results also suggest that the reactor configuration certainly influenced the microbial community,presumably leading to different ratios of phenol consumers and microorganisms feeding on degradation products.
文摘The increasing share of renewable energy in the electricity grid and progressing changes in power consumption have led to fluctuating,and weather-dependent power flows.To ensure grid stability,grid operators rely on power forecasts which are crucial for grid calculations and planning.In this paper,a Multi-Task Learning approach is combined with a Graph Neural Network(GNN)to predict vertical power flows at transformers connecting high and extra-high voltage levels.The proposed method accounts for local differences in power flow characteristics by using an Embedding Multi-Task Learning approach.The use of a Bayesian embedding to capture the latent node characteristics allows to share the weights across all transformers in the subsequent node-invariant GNN while still allowing the individual behavioral patterns of the transformers to be distinguished.At the same time,dependencies between transformers are considered by the GNN architecture which can learn relationships between different transformers and thus take into account that power flows in an electricity network are not independent from each other.The effectiveness of the proposed method is demonstrated through evaluation on two real-world data sets provided by two of four German Transmission System Operators,comprising large portions of the operated German transmission grid.The results show that the proposed Multi-Task Graph Neural Network is a suitable representation learner for electricity networks with a clear advantage provided by the preceding embedding layer.It is able to capture interconnections between correlated transformers and indeed improves the performance in power flow prediction compared to standard Neural Networks.A sign test shows that the proposed model reduces the test RMSE on both data sets compared to the benchmark models significantly.
基金the financial support provided by the National Natural Science Foundation of China(Grant No.42272310).
文摘Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity attenuation.This paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in sands.The solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil interaction.Model parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle breakage.The semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in sands.The results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in sands.The displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing effect.This methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2020B1111380003)Guangdong Provincial Programs for Science and Technology Development(2022A0505030006)+6 种基金National Natural Science Foundation of China(31970110,32370111)GDAS’Special Project of Science and Technology Development(2021GDASYL-20210103022)State Key Laboratory of Applied Microbiology Southern China(Grant SKLAM005-2020)Danish National Research Foundation(DNRF136)Zhenyu Wang(File No.202208080044)is financially supported by the China Scholarship CouncilLeonid Digel was supported by FEMS Research and Training Grant(1725)EMBO Scientific Exchange grant(9720)for a visit to the UFZ in Leipzig,Germany.
文摘At the sediment-water interfaces,filamentous cable bacteria transport electrons from sulfide oxidation along their filaments towards oxygen or nitrate as electron acceptors.These multicellular bacteria belonging to the family Desulfobulbaceae thus form a biogeobattery that mediates redox processes between multiple elements.Cable bacteria were first reported in 2012.In the past years,cable bacteria have been found to be widely distributed across the globe.Their potential in shaping the surface water environments has been extensively studied but is not fully elucidated.In this review,the biogeochemical characteristics,conduction mechanisms,and geographical distribution of cable bacteria,as well as their ecological effects,are systematically reviewed and discussed.Novel insights for understanding and applying the role of cable bacteria in aquatic ecology are summarized.
