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Topology impacts TRAIL therapy: Differences in primary cancer growth and liver metastasis between orthotopic and subcutaneous xenotransplants of pancreatic ductal adenocarcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2021年第3期20卷 279-284页

作者： Bastian Kettler Anna Trauzold Christian Röder jan-hendrik egberts Holger Kalthoff Clinic for General- Abdominal-and Transplant-SurgeryMedical School HannoverCarl-Neuberg-Str.130625 HannoverGermany Institute for Experimental Cancer Research University of Kiel and University Clinic of Schleswig-HolsteinCampus KielHs.U30Arnold-Heller-Str.324105 KielGermany Clinic for General VisceralThoracicTransplantation-and Pediatric SurgeryUniversity Clinic of Schleswig-HolsteinCampus KielHs.CArnold-Heller-Str.324105 KielGermany

Background: To study novel treatment modalities for pancreatic ductal adenocarcinoma(PDAC), we need to transfer the knowledge from in vitro to in vivo. It is important to mirror the clinical characteristics of the typically local invasive growth of pancreatic cancer and the distant spread resulting in liver metastasis. Notably, for xenotransplant studies using human specimen, two models, i.e. subcutaneous(s.c.) and orthotopic(o.t.) transplantation are widely used. Methods: The subcutaneously and orthotopically inoculated Colo357 Bcl-x L cell-derived tumors were directly compared with and without TNF-related apoptosis inducing ligand(TRAIL) treatment. The size of primary tumors, number of liver metastasis and the histologic markers Ki67, M30, TNF-α and CD31 were assessed. Results: Upon TRAIL treatment, the primary tumors did not change their size, neither in the s.c. nor in the o.t. approaches. But when s.c. was compared to o.t., the size of the s.c. tumors was more than twofold bigger than that of the o.t. tumors( P<0.01). However, mice with orthotopically inoculated PDAC cells developed liver metastasis upon TRAIL treatment much more frequently( n=13/17) than mice with subcutaneously inoculated PDAC cells( n=1/11)( P<0.01). As a likely driving force for this increased metastasis, a higher TNF-α staining intensity in the o.t. tumors was observed by immunohistochemistry. Conclusions: These data from a direct side-by-side comparison underline the importance of the proper inoculation site of the PDAC cells. Local invasion and liver metastases are a hallmark of PDAC in the clinic;the o.t. model is clearly superior in reflecting this setting. Moreover, a serious side-effect of a possible new therapeutic compound became obvious only in the o.t. model.

关键词： Pancreatic cancer Animal models Immunohistochemistry Subcutaneous metastasis

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Expression of L amino acid transport system 1 and analysis of iodine-123-methyltyrosine tumor uptake in a pancreatic xenotransplantation model using fused high-resolution-micro-SPECT-MRI

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Hepatobiliary & Pancreatic Diseases International 2011年第1期10卷 30-37页

作者： Corinna von Forstner Maaz Zuhayra Ole Ammerpohl Sanjay Tiwari Olav jansen Holger Kalthoff Eberhard Henze jan-hendrik egberts Department of Nuclear Medicine University Hospital of Schleswig-Holstein Institute for Experimental Cancer Research University Hospital of Schleswig-Holstein Institute of Neuroradiology University Hospital of Schleswig-Holstein Department of General Surgery and Thoracic Surgery University Hospital of Schleswig-Holstein

BACKGROUND:The specificity in discriminating pancreatitis is limited in the positron emission tomography(PET)using ***,PET is not widely available compared to the single photon emission computed tomography(SPECT).Since amino acids play a minor role in metabolism of inflammatory cells,the potential of the SPECT tracer,3-[ 123 I]iodo-L-α-methyltyrosine(123I-IMT),for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice. METHODS: 123 I-IMT was injected to eight mice inoculated with subcutaneous or orthotopic pancreatic *** high-resolution-micro-SPECT(Hi-SPECT)and magnetic resonance imaging were *** gene expression level of L amino acid transport-system 1(LAT1)was analyzed and correlated with tumor uptake of 123 I-IMT. RESULTS:A high uptake of 123 I-IMT was detected in all tumor-bearing *** median tumor-to-background ratio (T/B)was 12.1(2.0-13.2)for orthotopic and 8.4(1.8-11.1)for subcutaneous xenotransplantation,***, the LAT1 expression in transplanted Colo357 cells was increased compared to non-malignant ***:Our mouse model could show a high 123 I-IMT uptake in pancreatic *** MRI scans facilitate precise evaluation of uptake in the specific regions of *** studies are required to confirm these findings in tumors derived from other human pancreatic cancer *** amino acids play a minor role in the metabolism of inflammatory cells,the potential for application of 123 I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.

关键词： pancreatic ductal adenocarcinoma iodine-123-methyltyrosine high-resolution-micro-SPECT L amino acid transport-system 1 xenotransplantation model

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Littoral landforms of Lake Hulun and Lake Buir(China and Mongolia):Wind-driven hydro-sedimentary dynamics and resulting clastics distribution

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Journal of Palaeogeography 2024年第2期13卷 309-326页

作者： Li Wang Mathieu Schuster Shi-Wei Xin Florin Zainescu Xin-Yu Xue Joep Storms jan-hendrik May Alexis Nutz Helena van der Vegt Guilherme Bozetti Zai-Xing Jiang School of Energy Resources China University of Geosciences(Beijing)Beijing100083China Universite de Strasbourg CNRSENGEESInstitut Terre et Environnement de StrasbourgUMR 70635 Rue DescartesStrasbourgFrance Tamsag Mongolia(XIX)Ltd. PetroChinaDaqing 163000China CEREGE Aix-Marseille UniversitéCNESIRDCollege de FranceINRAAix en ProvenceFrance School of Marine Science Sun Yat-sen UniversityZhuhai 519083China Delft University of Technology Department of Geoscience and EngineeringDelfthe Netherlands School of Geography Earth and Atmospheric SciencesUniversity of Melbourne253 Elgin St.CarltonVIC 3053Australia Deltares Delfthe Netherlands SCMF Faculty of GeographyUniversity of Bucharest1 N.Balcescu Blv.BucharestRomania

Two rectangular-shaped lakes,Lake Hulun and Lake Buir,located at the boundary between China and Mongolia,only c.75 km apart and therefore experiencing similar wind fields,have been studied based on satellite images and field surveys in order to compare their geomorphological and sedimentological *** wind-driven hydrodynamics,which have a significant effect on the development of littoral landforms and on sediment distribution,have been discussed for the two similar lakes that experienced a prevailing wind perpendicular to their long axis.A conceptual model related to wind-driven water bodies and sediment distribution is ***-influenced to wave-dominated deltas,beaches,spits,and eolian dune deposits develop around these two lakes,with a strikingly similar distribution *** features locally inform the longshore drift and help reconstruct the water circulation induced by wind *** the NW prevailing wind regime,the spits developed on the SW coast with a NW—SE extension,which was influenced by the NW—SE longshore *** same influence was observed in the delta extension in the NE *** differences lie in the presence of fan deltas in the NW region of Lake Hulun,but not in Lake ***,the width of the beach and eolian deposits on the downwind coast of Lake Hulun is three times greater than that of Lake Buir which were caused by the differences in sediment supply and wind fetch between the two *** Hulun and Lake Buir provide two reliable examples to understand the relationship among the wind field,provenance,hydrodynamics,landforms,and asymmetrical distribution of clastics in elongated *** also represent relevant modern analogs,which may also be of guiding significance to wind-driven sand body prediction in lacustrine basins.

关键词： Wind-driven lakes Fetch Sedimentary facies Hydrodynamics Geomorphology Spits Shoreline Lake Hulun Lake Buir

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Role of mucosal dendritic cells in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第33期14卷 5138-5148页

作者： jan hendrik Niess Department of Internal Medicine I Ulm UniversityUlm 89031 Germany

The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

关键词： Dendritic cells Commensal Inflammatory bowel disease Mucosal immunity Host defence

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Combination of cold drawing and cryogenic turning for modifying surface morphology of metastable austenitic AISI 347 steel

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Journal of Iron and Steel Research International 2019年第11期26卷 1188-1198页

作者： hendrik Hotz Benjamin Kirsch Steven Becker Ralf Miiller jan CAurich Institute for Manufacturing Technology and Production Systems University of Kaiserslautern67663 KaiserslauternGermany Institute of Applied Mechanics University of Kaiserslautern67663 KaiserslauternGermany

The application of components often depends to a large extent on the properties of the surface layer.A novel process chain for the production of components with a hardened surface layer from metastable austenitic steel was *** investigated metastable austenitic AISI 347 steel was cold-drawn in solution annealed condition at cryogenic temperatures for pre-hardening,followed by post-hardening via cryogenic *** increase in hardness in both processes was due to strain hardening and deformation-induced phase transformation from y-austenite to^-*** turning experiments were carried out with solution annealed AISI 347 steel as well as with solution annealed and subsequently cold-drawn AISI 347 *** thermomechanical load of the workpiece surface layer during the turning process as well as the resulting surface morphology was *** forces and temperatures were higher in turning the cold-drawn AISI 347 steel than turning the solution annealed AISI 347 *** cryogenic turning of the solution annealed material,deformation-induced phase transformation and a significant increase in hardness were detected in the near-surface *** contrast,no additional phase transformation was observed after cryogenic turning of the cold-drawn AISI 347 *** maximum hardness in the surface layer was similar,whereas the hardness in the core of the cold-drawn AISI 347 steel was higher compared to that in the solution annealed AISI 347 steel.

关键词： Surface layer hardening Cryogenic turning Cold drawing Metastable austenitic steel Deformation-induced phase transformation

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Timings of early crustal activity in southern highlands of Mars:Periods of crustal stretching and shortening

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Geoscience Frontiers 2019年第3期10卷 1029-1037页

作者： Trishit Ruj Goro Komatsu jan hendrik Pasckert James M.Dohm International Research School of Planetary Sciences Università d'Annunzio Department of Earth and Planetary Science School of Science University of Tokyo Institut für Planetologie Westf?lische Wilhelms-Universit?t Foundation for Advancement of International Science

Extensional and compressional structures are globally abundant on Mars. Distribution of these structures and their ages constrain the crustal stress state and tectonic evolution of the planet. Here in this paper, we report on our investigation over the distribution of the tectonic structures and timings of the associated stress fields from the Noachis-Sabaea region. Thereafter, we hypothesize possible origins in relation to the internal/external processes through detailed morphostructural mapping. In doing so, we have extracted the absolute model ages of these linear tectonic structures using crater size-frequency distribution measurements, buffered crater counting in particular. The estimated ages indicate that the tectonic structures are younger than the mega impacts events(especially Hellas) and instead they reveal two dominant phases of interior dynamics prevailing on the southern highlands, firstly the extensional phase terminating around3.8 Ga forming grabens and then compressional phase around 3.5-3.6 Ga producing wrinkle ridges and lobate scarps. These derived absolute model ages of the grabens exhibit the age ca. 100 Ma younger than the previously documented end of the global extensional phase. The following compressional activity corresponds to the peak of global contraction period in Early Hesperian. Therefore, we conclude that the planet wide heat loss mechanism, involving crustal stretching coupled with gravitationally driven relaxation(i.e.,lithospheric mobility) resulted in the extensional structures around Late Noachian(around 3.8 Ga). Lately cooling related global contraction generated compressional stress ensuing shortening of the upper crust of the southern highlands at the Early Hesperian period(around 3.5-3.6 Ga).

关键词： Martian dynamics Southern highlands Extensional tectonics Compressional tectonics Age of structures Buffer crater counting

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Approximating multi-purpose AC Optimal Power Flow with reinforcement trained Artificial Neural Network

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能源与人工智能(英文) 2022年第1期7卷 131-141页

作者： Zhenqi Wang jan-hendrik Menke Florian Schäfer Martin Braun Alexander Scheidler Department of Energy Management and Power System Operation University of KasselWilhelmshöher Allee 7334121 KasselGermany Fraunhofer Institute for Energy Economics and Energy System Technology Königstor 5934119 KasselGermany

Solving AC-Optimal Power Flow(OPF)problems is an essential task for grid operators to keep the power system safe for the use cases such as minimization of total generation cost or minimization of infeed curtailment from renewable DERs(Distributed Energy Resource).Mathematical solvers are often able to solve the AC-OPF problem but need significant computation *** neural networks(ANN)have a good application in function approximation with outstanding computational *** this paper,we employ ANN to approximate the solution of AC-OPF for multiple *** novelty of our work is a new training method based on the reinforcement learning concept.A high-performance batched power flow solver is used as the physical environment for training,which evaluates an augmented loss function and the numerical action *** augmented loss function consists of the objective term for each use case and the penalty term for constraints *** training method enables training without a reference OPF and the integration of discrete decision variable such as discrete transformer tap changer position in the constrained *** improve the optimality of the approximation,we further combine the reinforcement training approach with supervised training labeled by reference *** benchmark results show the high approximation quality of our proposed approach while achieving high computational efficiency on multiple use cases.

关键词： OPF Artificial neural network Reinforcement learning Grid planning and operation Grid congestion management

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Spatial heterogeneity of flesh-cell osmotic potential in sweet cherry affects partitioning of absorbed water

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Horticulture Research 2020年第1期7卷 2104-2113页

作者： Eckhard Grimm Daniel Pflugfelder jan Hahn Moritz Jonathan Schmidt hendrik Dieckmann Moritz Knoche Institut für Gartenbauliche Produktionssysteme Leibniz Universität HannoverAbteilung ObstbauHerrenhäuser Straße 2D-30419 HannoverGermany Forschungszentrum Jülich IBG-2:PflanzenwissenschaftenWilhelm-Johnen-StraßeD-52428 JülichGermany Laser Zentrum Hannover e.V. Hollerithallee 8D-30419 HannoverGermany

A fleshy fruit is commonly assumed to resemble a thin-walled pressure vessel containing a homogenous carbohydrate *** sweet cherry(Prunus avium L.)as a model system,we investigate how local differences in cell water potential affect H2O and D2O(heavy water)*** partitioning of H2O and D2O was mapped nondestructively using magnetic resonance imaging(MRI).The change in size of mesocarp cells due to water movement was monitored by optical coherence tomography(OCT,non-destructive).Osmotic potential was mapped using microosmometry(destructive).Virtual sections through the fruit revealed that the H2O distribution followed a net pattern in the outer mesocarp and a radial pattern in the inner *** patterns align with the disposition of the vascular bundles.D2O uptake through the skin paralleled the acropetal gradient in cell osmotic potential gradient(from less negative to more negative).Cells in the vicinity of a vascular bundle were of more negative osmotic potential than cells more distant from a vascular *** revealed net H2O uptake was the result of some cells loosing volume and other cells increasing volume.H2O and D2O partitioning following uptake is non-uniform and related to the spatial heterogeneity in the osmotic potential of mesocarp cells.

关键词： potential Spatial bundle

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Descemet-membrane endothelial keratoplasty in patients with retinal comorbidity -a prospective cohort study

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International Journal of Ophthalmology(English edition) 2016年第3期9卷 390-394页

作者： Kristina Spaniol Christoph Holtmann jan-hendrik Schwinde Sophia Deffaa Rainer Guthoff Gerd Geerling University Eye Hospital Dusseldorf Moorenstraβe 5Dusseldorf 40225 Germany

AIM： To investigate indications, surgical challenges, and outcome of Descemet -membrane endothelial keratoplasty （DMEK） in patients with retinal comorbidities （RC）. METHODS： In a prospective cohort study, 8 eyes of 8 DMEK-patients with known RC were compared to 38 eyes of 38 DMEK-patients without RC. The duration of surgery, the degree of difficulty graded by the surgeon, and the complications through DMEK-surgery were analyzed for each patient. The best-corrected visual acuity （BCVA）, the endothelial cell count, the intraocular pressure, and the subjective satisfaction was evaluated after a 6-month follow-up. Data were compared applying the non-parametric Wilcoxon-, Chi-square- and Fisher＇s-exact-test with P≤ 0. 05 as level of significance. RESULTS： RC-patients had dry age-related macular degeneration （n=4） or history of pars-plana vitrectomy （n=4）. The main indication for DMEK was pain due to bullous keratopathy for the RC-patlents （n=7, 88%） and visual impairment due to Fuchs endothelial keratoplasty for the non-RC-patients （n=33, 87% ）. The BCVA increased for both groups （P=0.01, P〈0.001） and all corneas cleared. For the RC-patients, the subjective satisfaction improved significantly （P=0.02）. Oil-filling and missing support of the vitreous body complicated surgery in vitrectomized eyes. CONCLUSION： DMEK is a favorable technique to treat endothelial disorders even if patients suffer from a retinal comorbidity. By enhancing the corneal clarity, it enables retinal examination or intraocular surgery and increases the patients satisfaction. However, in vitrectomized or silicone-oil filled eyes, the duration of surgery and degree of complexity are increased. An experienced surgeon should perform DMEK in these patients. Clinical trial registration number： DRKS00007566.

关键词： Descemet-membrane endothelial keratoplasty age-related macular degeneration pars plana vitrectomy

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Early detection of neuropathy in leprosy:a comparison of five tests for field settings

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Infectious Diseases of Poverty 2017年第1期6卷 1034-1042页

作者： Inge Wagenaar Erik Post Wim Brandsma Dan Ziegler Moshiur Rahman Khorshed Alam jan hendrik Richardus Department of Public Health Erasmus MCRotterdamThe Netherlands KIT Health Royal Tropical InstituteAmsterdamThe Netherlands Independent leprosy consultant AmsterdamThe Netherlands Institute for Clinical Diabetology German Diabetes Center at Heinrich Heine UniversityLeibniz Center for Diabetes ResearchDusseldorfGermany Department of Endocrinology and Diabetology Medical FacultyHeinrich Heine UniversityDüsseldorfGermany Rural Health Program The Leprosy Mission International-BangladeshNilphamariBangladesh

Background:Early detection and treatment of neuropathy in leprosy is important to prevent disabilities.A recent study showed that the Nerve Conduction Studies(NCS)and Warm Detection Thresholds(WDT)tests can detect leprosy neuropathy the *** two tests are not practical under field conditions,however,because they require climate-controlled rooms and highly trained staff and are *** assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early ***:Through a literature search we identified five alternative devices that appeared user-friendly,more affordable,portable and/or battery-operated:the Neuropad^(■),Vibratip^(TM),NC-Stat^(■)DPNCheck^(TM),NeuroQuick and the Thermal Sensibility Tester(TST),assessing respectively sweat function,vibration sensation,nerve conduction,cold sensation and warm *** leprosy patients in Bangladesh,the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard *** alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected *** and specificity were the main ***:The NeuroQuick and the TST showed very good sensitivity and *** the sural nerve,the NeuroQuick had both a sensitivity and a specificity of 86%.The TST had a sensitivity of 83%and a specificity of 82%.Both the NC-Stat^(■)DPNCheck^(TM)and Vibratip^(TM)had a high specificity(88%and 100%),but a low sensitivity(16%and 0%).On the posterior tibial nerve,the NeuroQuick and the TST also showed good sensitivity,but the sensitivity was lower than for the sural *** Neuropad^(■)had a sensitivity of 56%and a specificity of 61%.Conclusions:The NeuroQuick and TST are good candidates for further field-testing for reliability and *** feasibility of production on a larger scale should be exami

关键词： Leprosy Neuropathy Detection Subclinical Field use

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