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Ultra-sensitive bioanalysis of the therapeutic peptide exenatide for accurate pharmacokinetic analyses at effective plasma concentrations utilizing UPLC-MS/MS

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Journal of Pharmaceutical Analysis 2020年第3期10卷 233-239页

作者： Max Sauter philipp Uhl Jürgen Burhenne Walter E.Haefeli Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University HospitalIm Neuenheimer Feld 41069120HeidelbergGermany

Exenatide is the first approved glucagon-like peptide 1 receptor agonist subcutaneously or intramuscularly injected for the treatment of type 2 diabetes *** therapeutic plasma concentrations are in the low pg/mL range,therefore requiring ultra-sensitive *** enable the accurate evaluation of pharmacokinetic studies,we established a UPLC-MS/MS assay with a lower limit of quantification(LLOQ)of 5 pg/mL(1.2 pM)using 200μL of plasma,validated acco rding to FDA's and EMA's pertinent *** was isolated from plasma with solid phase extraction utilizing anionexchange *** was performed with positive electrospray ionization tandem mass spectrometry in the selected reaction monitoring *** calibrated concentration range of 5-10,000 pg/mL was linear showing co rrelation coefficients>*** and intraday accuracy ranged from 97.5%to 105.4%with corre sponding precision of<10.9%.Accuracy at the LLOQ ranged from 93.0%to 102.5%with corresponding precision of<15.9%.Because of the validity of a 10-fold dilution QC(accuracy 111.2%),the assay is suitable for exenatide quantification up to 100,000 pg/*** ultra-sensitive assay's applicability was demonstrated by the quantification of exenatide plasma concentrations and pharmacokinetics after intravenous and nasal administration to beagle dogs.

关键词： Exenatide Nasal Intravenous UPLC Tandem mass spectrometry Pharmacokinetics

Modeling height–diameter relationship for Populus euphratica in the Tarim riparian forest ecosystem, Northwest China

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Journal of Forestry Research 2016年第4期27卷 889-900页

作者： Tayierjiang Aishan Umüt Halik Florian Betz philipp Gartner Bernd Cyffka Key Laboratory of Oasis Ecology College of Resources &Environmental Sciences Xijiiang UniversityUrumqi 830046 China Faculty of Mathematics and Geography Catholic University of Eichstaett-Ingolstadt 85072 Eichstaett Germany Geoinformation in Environmental Planning Lab Technical University of Berlin 10623 Berlin Germany

Modeling height–diameter relationships is an important component in estimating and predicting forest development under different forest management scenarios. In this paper, ten widely used candidate height–diameter models were fitted to tree height and diameter at breast height（DBH）data for Populus euphratica Oliv. within a 100 ha permanent plots at Arghan Village in the lower reaches of the Tarim River, Xinjiang Uyghur Autonomous Region of China. Data from 4781 trees were used and split randomly into two sets：75 % of the data were used to estimate model parameters（model calibration）, and the remaining data（25 %） were reserved for model validation. All model performances were evaluated and compared by means of multiple model performance criteria such as asymptotic t-statistics of model parameters, standardized residuals against predicted height,root mean square error（RMSE）, Akaike’s informationcriterion（AIC）, mean prediction error（ME） and mean absolute error（MAE）. The estimated parameter a for model（6） was not statistically significant at a level of a = 0.05. RMSE and AIC test result for all models showed that exponential models（1）,（2）,（3） and（4） performed significantly better than others. All ten models had very small MEs and MAEs. Nearly all models underestimated tree heights except for model（6）. Comparing the MEs and MAEs of models, model（1） produced smaller MEs（0.0059） and MAEs（1.3754） than other models. To assess the predictive performance of models, we also calculated MEs by dividing the model validation data set into 10-cm DBH classes. This suggested that all models were likely to create higher mean prediction errors for tree DBH classes[20 cm. However, no clear trend was found among ***（6） generated significantly smaller mean prediction errors across all tree DBH classes. Considering all the aforementioned criteria, model（1）： TH ？ 1：3 t a= e1 t b？eàc？DBHT and model（6）： TH ？ 1：3 t DBH2= ea t b？DBH t c ？ DBH2T are recommended as suitable models for de

关键词： calibration shortcomings absolute dividing exponential fitting candidate permanent fitted estimating

Long-Lasting Stretching Induces Muscle Hypertrophy:A Meta-Analysis of Animal Studies

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Journal of Science in Sport and Exercise 2023年第4期5卷 289-301页

作者： Konstantin Warneke philipp Alexander Freund Stephan Schiemann Institute for Exercise Sport and HealthLeuphana UniversityUniversitätsallee 1LüneburgGermany Institute of Psychology Leuphana UniversityLüneburgGermany

Muscular hypertrophy depends on metabolic exhaustion as well as mechanical load on the *** tension seems to be the crucial factor to stimulate protein *** present meta-analysis was conducted to determine whether stretching can generate adequate mechanical tension to induce muscle *** used PubMed,Web of Science,and Scopus to search for literature examining the effects of long-term stretching on muscle mass,muscle cross-sectional area,fiber cross-sectional area,and fiber *** there was no sufficient number of studies investigating long-lasting stretching in humans,we only included original animal studies in the current ***,we identified 16 studies meeting the inclusion criteria(*** of at least 15 min per day).The 16 studies yielded 39 data points for muscle mass,11 data points for muscle cross-sectional area,20 data points for fiber cross-sectional area,and 10 data points for fiber *** all designs and categories,statistically significant increases were found for muscle mass(d=8.51;95%CI 7.11-9.91),muscle cross-sectional area(d=7.91;95%CI 5.75-10.08),fiber cross-sectional area(d=5.81;95%CI 4.32-7.31),and fiber number(d=4.62;95%CI 2.54-6.71).The findings show an(almost)continuous positive effect of long-term stretching on the listed parameters,so that it can be assumed that stretch training with adequate intensity and duration leads to hypertrophy and hyperplasia,at least in animal studies.A general transferability to humans-certainly with limited effectiveness-can be hypothesized but requires further research and training studies.

关键词： Muscle mass Static stretching Hyperplasia Chronic stretching

Interplay between microstructural evolution and tribo-chemistry during dry sliding of metals

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Friction 2019年第6期7卷 637-650页

作者： philipp GGRÜTZMACHER Sebastian RAMMACHER Dominic RATHMANN Christian MOTZ FrankMÜCKLICH Sebastian SUAREZ Chair of Functional Materials Saarland UniversityCampus D3.3Saarbrücken 66123Germany Chair of Experimental Methodology of Material Science Saarland UniversityCampus D2.2Saarbrücken 66123Germany

Understanding the microstructural and tribo-chemical processes during tribological loading is of utmost importance to further improve the tribological behavior of metals. In this study, the friction, wear and tribo-chemical behavior of Ni with different initial microstructures(nanocrystalline, bi-modal, coarse-grained) is investigated under dry sliding conditions. In particular, the interplay be-tween frictional response, microstructural evolution and tribo-oxidation is considered. Friction tests are carried out using ball-on-disk experiments with alumina balls as counter-bodies, varying the load between 1 and 5 N. The microstructural evolution as well as the chemical reactions beneath the samples’ surface is investigated by means of cross-sections. The samples with finer microstructures show a faster run-in and lower maximum values of the coefficient of friction(COF) which can be attributed to higher oxidation kinetics and a higher hardness. It is observed that with increasing sliding cycles, a stable oxide layer is formed. Furthermore, initially coarse-grained samples show grain refinement, whereas initially finer microstructures undergo grain coarsening converging towards the same superficial grain size after 2,000 sliding cycles. Consequently, the experimental evidence supports that, irrespective of the initial microstructure, after a certain deformation almost identical steady-state COF values for all samples are achieved.

关键词： dry sliding microstructural analysis tribo‐oxidation wear

Liver surgery in cirrhosis and portal hypertension

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World Journal of Gastroenterology 2016年第9期22卷 2725-2735页

作者： Christina Hackl Hans J Schlitt philipp Renner Sven A Lang Department of Surgery University Medical Center Regensburg

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary ormetastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

关键词： Liver resection Hepatocellular carcinoma Liver metastases Portal hypertension Cholangiocellular carcinoma Cirrhosis

The fit of planning methods for the part manufacturing industry,a case study

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Advances in Manufacturing 2014年第2期2卷 165-172页

作者： philipp Spenhoff Marco Semini Erlend Alfnes Jan Ola Strandhagen Department of Production and Quality Engineering Norwegian University of Science and TechnologyTrondheimNorway Department of Industrial Management SINTEF Technology and SocietyTrondheimNorway

This paper investigates the specific planning environment of an automotive part manufacturer and characterizes this environment based on variables regarding the product,its demand and the manufacturing *** fit of different planning methods,namely material requirements planning,reorder point,cyclic planning,kanban,and heijunka to this specific planning environment is analyzed and evaluated by exploratory *** results show that different product characteristics make it hard to apply a single planning *** of the investigated methods show the ability to cover the complex requirements of a combined planning environment of two partly divergent product types with a deep value chain.

关键词： Production planning environment Production planning methods Automotive part manufacturing

Effects of newly devised plasma lice comb on human hair

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Plasma Science and Technology 2019年第12期21卷 78-84页

作者： Lars TEN BOSCH Andreas HUBER philipp SAUERBIER Robert KOHLER Georg AVRAMIDIS Wolfgang VIOL University of Applied Sciences and Arts HAWK Faculty NVon-Ossietzky-Strasse 99/10037085 GottingenGermany Neaspec GmbH Eglfinger Weg 285540 Munich-HaarGermany Wood Biology and Wood Products Faculty of Forest Sciences and Forest EcologyUniversity of GoettingenBüsgenweg 437077 GottingenGermany

A plasma device was developed showing high potential for a pesticide-free treatment of pediculosis. As a first safety assessment of the device was presented earlier, this present paper focuses on the damage introduced to human hair during a plasma treatment for pediculosis control. Therefore, human hairs were treated repeatedly to assess the possible occurring damage developing with increasing treatment durations. To analyse the inflicted changes on human hair examinations using x-ray photoelectron spectroscopy(XPS/ESCA), scanning nearfield optical microscopy(SNOM) and scanning electron microscopy were conducted, to compare the modifications of surface chemistry and mechanical alterations. The investigations revealed a mild impact on the surface chemistry(XPS/SNOM), while more distinct morphological changes on the hair surface could be observed. The authors conclude that an effect of the plasma comb device on the hair during a real-life treatment is negligible, due to the very short contact times during a standard combing procedure for pediculosis control.

关键词： atmospheric pressure plasma dielectric barrier discharge pediculosis SEM SNOM ESCA XPS hair smoothing plasma based pest management

A visual analytics workflow for probabilistic modeling

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Visual Informatics 2023年第2期7卷 72-84页

作者： Julien Klaus Mark Blacher Andreas Goral philipp Lucas Joachim Giesen Friedrich Schiller University Jena Germany

Probabilistic programming is a powerful means for formally specifying machine learning *** inference engine of a probabilistic programming environment can be used for serving complex queries on these *** of the current research in probabilistic programming is dedicated to the design and implementation of highly efficient inference *** less research aims at making the power of these inference engines accessible to non-expert *** programming means writing *** many potential users from promising application areas such as the social sciences lack programming *** prompted recent efforts in synthesizing probabilistic programs directly from ***,working with synthesized programs still requires the user to read,understand,and write some code,for instance,when invoking the inference engine for answering ***,we present an interactive visual approach to synthesizing and querying probabilistic programs that does not require the user to read or write code.

关键词： Probabilistic inference Bayesian network Structured query language Table-based visualization

Prodromal Parkinson’s disease: hype or hope for disease-modification trials?

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Translational Neurodegeneration 2022年第1期11卷 777-789页

作者： philipp Mahlknecht Kathrin Marini Mario Werkmann Werner Poewe Klaus Seppi Department of Neurology Innsbruck Medical University6020 InnsbruckAustria

The ultimate goal in Parkinson’s disease (PD) research remains the identification of treatments that are capable of slowing or even halting the progression of the disease. The failure of numerous past disease-modification trials in PD has been attributed to a variety of factors related not only to choosing wrong interventions, but also to using inadequate trial designs and target populations. In patients with clinically established PD, neuronal pathology may already have advanced too far to be modified by any intervention. Based on such reasoning, individuals in yet prediagnostic or prodromal disease stages, may provide a window of opportunity to test disease-modifying strategies. There is now sufficient evidence from prospective studies to define diagnostic criteria for prodromal PD and several approaches have been studied in observational cohorts. These include the use of PD-risk algorithms derived from multiple established risk factors for disease as well as follow-up of cohorts with single defined prodromal markers like hyposmia, rapid eye movement sleep behavior disorders, or PD gene carriers. In this review, we discuss recruitment strategies for disease-modification trials in various prodromal PD cohorts, as well as potential trial designs, required trial durations, and estimated sample sizes. We offer a concluding outlook on how the goal of implementing disease-modification trials in prodromal cohorts might be achieved in the future.

关键词： Neuroprotection Preclinical Prevention Epidemiology Probability Randomized controlled trial Preventive Neuroprotective