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“Clone-specific”antibody-drug conjugates:an innovative strategy in the treatment of T-cell cancers

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Signal Transduction and Targeted Therapy 2024年第10期9卷 4149-4150页

作者： Dennis Jungherz philipp Lückemeier Marco Herling Department of Hematology Cellular TherapyHemostaseology and Infectious DiseasesUniversity of Leipzig Medical CenterLeipzigGermany

In a recent study published in Nature,Nichakawade et *** proof-of-principle data on innovative strategies to target and eliminate cancerous T-cells while sparing healthy T-lymphocytes,addressing the urgent clinical need posed by the mostly aggressive and treatment-refractory T-cell lymphomas.1 This research represents a significant milestone in overcoming major obstacles in immunotherapies for these cancers.

关键词： treatment eliminate mostly

Anisotropic brittle-ductile transition of monocrystalline sapphire during orthogonal cutting and nanoindentation experiments

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Nanotechnology and Precision Engineering 2018年第3期1卷 157-171页

作者： philipp Maas Yuta Mizumoto Yasuhiro Kakinuma Sangkee Min Department of System Design Engineering Faculty of Science & TechnologyKeio University Department of Mechanical Engineering University of Wisconsin-Madison

Single-crystal sapphire is utilized as a high-performance engineering material,especially in extreme and harsh ***,due to its extreme hardness and brittleness,the machinability of sapphire is still a *** means of nanoindentation and plunge-cut experiments,the anisotropic brittle-ductile transition of the prismatic M-plane and rhombohedral R-plane is examined by analyzing crack morphologies and the critical depth-of-cut(CDC).The experimental results of the nanoindentation tests are correlated to the plunge-cut *** the prism plane and the rhombohedral crystal plane exhibit a two-fold symmetry of ductility with various crack patterns along the machined *** direction-dependent plasticity of the hexagonal sapphire crystal is mainly connected to a twinning process accompanied by slip dislocation.

关键词： Sapphire Anisotropy Brittle-ductile transition Orthogonal cutting

CFD–DEM simulation of fine particles in a spouted bed apparatus with a Wurster tube

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Particuology 2019年第1期17卷 114-125页

作者： Paul Breuninger Dominik Weis Isabell Behrendt philipp Grohn Fabian Krull Sergiy Antonyuk Institute of Particle Process Engineering University of KaiserslauternGottlieb Daimler Str.. KaiserslauternGermany

In this work, a coupled computational fluid dynamics–discrete element method (CFD–DEM) approach was employed to evaluate the spouting behavior of fine, cohesive powders in a cylindrical spouted bed with a conical base and equipped with a Wurster tube. The particle and gas dynamics inside the apparatus were simulated with 1.7 million spherical ZrO2 particles with a particle size of 100 μm. For an accurate prediction of the interactions of cohesive particles in the spouted bed, the adhesion forces according to JKR theory were included in the Hertz–Tsuji contact model. The surface energy of the particles was varied over a wide range to determine the effect of the adhesion on the spouting (the fountain shape and maximum height as well as the distribution of the concentrations and velocities of particles in different zones of the apparatus). A detailed analysis of the collision dynamics was conducted. The spouting behavior of a spouted bed with the same dimensions, particles, and processing parameters was recorded with a high-speed camera. The CFD–DEM simulations showed good agreement with the experimentally captured spouting behavior.

关键词： CFD–DEM Spouted bed Wurster tube Cohesive powder

Second premolar agenesis is associated with mandibular form： a geometric morphometric analysis of mandibular cross-sections

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International Journal of Oral Science 2016年第4期8卷 254-260页

作者： Michael H Bertl Kristina Bertl Manuel Wagner Andre Gahleitner Andreas Stavropoulos christian Ulm philipp Mitteroecker Division of Orthodontics School of Dentistry Medical University of Vienna Vienna Austria Department of Periodontology Faculty of Odontology University of Malmo MalmoSweden Division of Oral Surgery School of Dentistry Medical University of Vienna Vienna Austria Department of Diagnostic Radiology Division of Osteoradiology General Hospital Medical University of Vienna Vienna Austria Department of Theoretical Biology University of Vienna Vienna Austria

The aim of this study was to compare mandibular form （i.e., size and shape） between patients with agenesis of the lower second premolar （P2） and a control group with no agenesis. Three hypotheses were tested：（H1） agenesis causes a change in mandibular morphology because of inadequate alveolar ridge development in the area of the missing tooth （mandibular plasticity）; （H2） agenesis is caused by spatial limitations within the mandible （dental plasticity）; and （H3） common genetic/ epigenetic factors cause agenesis and affect mandibular form （pleiotropy）. A geometric morphometric analysis was applied to cross-sectional images of computed tomography （CT） scans of three matched groups （n= 50 each）：（1） regularly erupted P2; （2） agenesis of P2 and the primary second molar in situ; and （3） agenesis of P2 and the primary second molar missing for 〉3 months. Cross-sections of the three areas of interest （first premolar, P2, first molar） were digitized with 23 landmarks and superimposed by a generalized Procrustes analysis. On average, the mandibular cross-sections were narrower and shorter in patients with P2 agenesis compared with that in the control group. Both agenesis groups featured a pronounced submandibular fossa. These differences extended at least one tooth beyond the agenesis-affected region. Taken together with the large interindividual variation that resulted in massively overlapping group distributions, these findings support genetic and/or epigenetic pleiotropy （H3） as the most likely origin of the observed covariation between mandibular form and odontogenesis. Clinically, reduced dimensions and greater variability of mandibular form, as well as a pronounced submandibular fossa, should be expected during the treatment planning of patients with P2 agenesis.

关键词： agenesis cross-sections geometric morphometrics mandibular form

Molecular insights of exercise therapy in disease prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2564-2597页

作者： David Walzik Tiffany Y.Wences Chirino philipp Zimmer Niklas Joisten Division of Performance and Health(Sports Medicine) Institute for Sport and Sport ScienceTU Dortmund University44227 DortmundNorth Rhine-WestphaliaGermany Division of Exercise and Movement Science Institute for Sport ScienceUniversity of Göttingen37075 GöttingenLower SaxonyGermany

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases,the underlying biological mechanisms have not been fully *** exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle,cardiac muscle,adipose,and liver *** signaling molecules,which are collectively termed exerkines,form a heterogenous group of bioactive substances,mediating inter-organ crosstalk as well as structural and functional tissue *** scientific endeavors have focused on identifying and characterizing new biological mediators with such ***,some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes.A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and ***,we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various *** emphasizing different aspects of exerkine research,we provide a comprehensive overview of(i)the molecular underpinnings of exerkine secretion,(ii)the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption,and(iii)the clinical implications of these mechanisms in disease prevention and treatment.

关键词： prevention treatment collective

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

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

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