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Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

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World journal of Gastroenterology 2008年第24期14卷 3819-3828页

作者： Maike Sieben Kerstin Herzer Maja Zeidler Vera Heinrichs Barbara Leuchs Martin Schuler jan j cornelis Peter R Galle jean Rommelaere Markus Moehler First Department of Internal Medicine Johannes Gutenberg University of Mainz German Cancer Research Center Infection and Cancer ProgramDept.F010 and Institut National de la Santé et de la Recherche Médicale Unité 701 Department of Medicine (Cancer Research) West German Cancer CenterUniversity Hospital Essen

AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.

关键词： Autonomous parvovirus Apoptosis p53 Promyelooltic leukemia protein Human hepatocellularcarcinoma Hepatooltes

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Electrodynamics of Abrikosov vortices： the field theoretical formulation

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Frontiers of physics 2011年第4期6卷 357-369页

作者： Aron j. Beekman jan Zaanen Instituut-Lorentz for Theoretical Physics Universiteit Leiden P. O. Box 9506 2300 RA Leiden The Netherlands

Electrodynamic phenomena related to vortices in superconductors have been studied since their prediction by Abrikosov, and seem to hold no fundamental mysteries. However, most of the effects are treated separately, with no guiding principles. We demonstrate that the relativistic vortex worldsheet in spacetime is the object that naturally conveys all electric and magnetic information, for which we obtain simple and concise equations. Breaking Lorentz invariance leads to down-to-earth Abrikosov vortices, and special limits of these equations include for instance dynamic Meissner screening and the AC josephson relation. On a deeper level, we explore the electrodynamics of two-form sources in the absence of electric monopoles, in which the electromagnetic field strength itself acquires the characteristics of a gauge field. This novel framework leaves room for unexpected surprises .

关键词： Abrikosov vortex, electromagnetism, Maxwell equations, differential geometry multivalued fields

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Sediment generation and soil mound denudation in areas of high-density tree throw along a river valley in the jura Mountains, Switzerland

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journal of Mountain Science 2021年第2期18卷 377-391页

作者： Philip GREENWOOD jan BAUER Nikolaus j KUHN Physical Geography&Environmental Change Research Group Department of Environmental SciencesUniversity of BaselKlingelbergstrasse 27Basel-4056Switzerland

A preliminary field-based investigation was undertaken in a small(<10 km^(2))river valley located in the mountainous jura region of northwest *** aims of the work were to assess sediment generation and annual sediment... 详细信息

A preliminary field-based investigation was undertaken in a small(jura region of northwest *** aims of the work were to assess sediment generation and annual sediment transport rates by tree throw on forested hillslopes,and to document surface hydrology characteristics on four fresh soil mounds associated with recent tree throws over a 24-day monitoring *** the soil mounds,average sediment recovery ranged from 7.7-28.2 g(dry weight),equivalent to a suspended sediment concentration of 145.2-327.8 g L^(-1),and runoff coefficients ranged from 1.0%-4.2%.Based on a soil bulk density value of 1,044 kg m^(-3),upslope runoff generation areas were denuded by an average 0.14 mm by the end of the 24-day monitoring period,representing an erosion rate equivalent to 2.1 mm yr^(-1).A ca.50 cm high soil mound could therefore feasibly persist for around 200-250 *** tree throw work,the dimensions of 215 individual tree throws were measured and their locations mapped in 12 separate locations along the river valley representing a cumulative area equivalent to 5.3 ha(***,43 per ha).Tree throws generated a total of 20.1 m^(3) of fine-sediment(jority of tree throws,but instead,could be associated with root *** the high density of tree throws and their relative maturity(average age 41 years),we hypothesise that once tr

关键词： Tree throw Hillslope processes Sediment generation mechanism Sediment transport rate Soil mound Ibach river valley

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Validating neural networks for spectroscopic classification on a universal synthetic dataset

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npj Computational Materials 2023年第1期9卷 1325-1336页

作者： jan Schuetzke Nathan j.Szymanski Markus Reischl Institute for Automation and Applied Informatics Karlsruhe Institute of TechnologyKarlsruhe 76131Germany Department of Materials Science&Engineering Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Materials Science&Engineering UC BerkeleyBerkeleyCA 94720USA

To aid the development of machine learning models for automated spectroscopic data classification,we created a universal synthetic dataset for the validation of their *** dataset mimics the characteristic appearance of experimental measurements from techniques such as X-ray diffraction,nuclear magnetic resonance,and Raman spectroscopy among *** applied eight neural network architectures to classify artificial spectra,evaluating their ability to handle common experimental *** all models achieved over 98%accuracy on the synthetic dataset,misclassifications occurred when spectra had overlapping peaks or *** found that non-linear activation functions,specifically ReLU in the fully-connected layers,were crucial for distinguishing between these classes,while adding more sophisticated components,such as residual blocks or normalization layers,provided no performance *** on these findings,we summarize key design principles for neural networks in spectroscopic data classification and publicly share all scripts used in this study.

关键词： spectroscopic adding classify

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Role of human epidermal growth factor receptor 2 in gastric cancer:Biological and pharmacological aspects

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World journal of Gastroenterology 2014年第16期20卷 4526-4535页

作者： jan Tr?st j?rgensen Dx-Rx Institute 3480 FredensborgDenmark

Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in rela

关键词： Human epidermal growth factor receptor 2 Gastric cancer Prognostic Companion diagnostics Trastuzumab Pertuzumab Ado-trastuzumab emtansine Lapatinib

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Clear cell colitis: A form of microscopic colitis in children

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World journal of Gastroenterology 2008年第2期14卷 231-235页

作者： jan józefczuk Bogdan Marian Wozniewicz Pediatric Division City Hospital 39-360 Nowa Deba M. Curie Sklodowska 1 Poland Department of Pathology The Children’s Memorial Health Institute Aleja Dzieci Polskich 20 Warsaw 04-730 Poland

AIM: To describe a new clinical and pathological subtype of microscopic colitis in children. METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described. RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple’s disease), and neuronal intestine dysplasia. Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages. CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis, sometimes coexisting with allergy.

关键词： Microscopic colitis Clear cell colitis Diarrhoea Constipation Abdominal pain Children Allergy Endoscopy

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Diagnostic yield of small bowel capsule endoscopy depends on the small bowel transit time

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World journal of Gastroenterology 2012年第13期18卷 1502-1507页

作者： jessie Westerhof jan j Koornstra Reinier A Hoedemaker Wim j Sluiter jan H Kleibeuker Rinse K Weersma Department of Gastroenterology and Hepatology University Medical Center GroningenUniversity of GroningenPO Box 300019700 RBGroningenThe Netherlands

AIM： To investigate whether the small bowel transit time （SBTT） influences the diagnostic yield of capsule endoscopy （CE）. METHODS： Six hundred and ninety-one consecutive CE procedures collected in a database were analyzed. SBTT and CE findings were recorded. A running mean for the SBl-I- was calculated and correlated to the diagnostic yield with a Spearman＇s correlation test. Subgroup anal- yses were performed for the various indications for the procedure. RESULTS： There was a positive correlation between the diagnostic yield and SBT1- （Spearman＇s rho 0.58, P 〈 0.01）. Positive correlations between diagnostic yield and SB-FI-were found for the indication obscure gastro- intestinal bleeding （r = 0.54, P 〈 0.01）, for polyposis and carcinoid combined （r = 0.56, P 〈 0.01） and for the other indications （r = 0.90, P 〈0.01）, but not for suspected Crohn＇s disease （r = -0.40） CONCLUSION： The diagnostic yield in small bowel capsule endoscopy is positively correlated with the small bowel transit time. This is true for all indications except for suspected Crohn＇s disease.

关键词： Capsule endoscopy Small bowel transit time Diagnostic yield

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Management of rectal foreign bodies: Description of a new technique and clinical practice guidelines

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World journal of Gastroenterology 2008年第27期14卷 4403-4406页

作者： jan j Koornstra Rinse K Weersma Department of Gastroenterology & Hepatology University Medical Centre Groningen University of Groningen

A number of techniques have been described to remove rectal foreign bodies. In this report, a novel endoscopic technique using a pneumatic dilatation balloon normally used in achalasia patients is presented. In addition, a systematic review of the literature was performed for non-operative methods to remove foreign bodies from the rectum. These results are summarised, presented as a practical at-a- glance overview and a flow chart is offered to guide the clinician in treatment decisions. The design of the flow chart was based on the aims to treat the patient preferably on an outpatient basis with minimally invasive techniques and if possible under conscious sedation rather than general anaesthesia.

关键词： Foreign body Rectum Rectal Removal Review

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Inhibitory effects of interferons on pancreatic stellate cell activation

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World journal of Gastroenterology 2006年第6期12卷 896-901页

作者： jan-TidoBaumert GiselaSparmann j rgEmmrich StefanLiebe Robertjaster Department of Me-dicine Division of GastroenterologyMedical FacultyUniversity of RostockE-Heydemann-Str.618057 Rostock Germany

AIM： To analyze and to compare the effects of interferon （IFN）-α, IFN-β, and IFN-γ on pancreatic stellate cell （PSC） activation/n vitro and to elucidate the molecular basis of IFN action. METHODS： PSCs were isolated from rat＇s pancreatic tissue, cultured and stimulated with recombinant rat IFNs. Cell proliferation and collagen synthesis were assessed by measuring the incorporation of 5-bromo-2＇ -deoxyuridine （BrdU） into DNA and [^3H]-proline into acetic acid-soluble proteins, respectively. Apoptotic ceils were determined by FACS analysis （sub-G1 peak method）. Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of （α-smooth muscle actin （α-SMA） expression. To assess the activation of signal transducer and activator of transcription （STAT）, Western blots using phospho- STAT-specific antibodies were performed. In studies on STAT1 function, expression of the protein was inhibited by siRNA. RESULTS： IFN-β and IFN-γ, but not IFN-α significantly diminished PSC proliferation and collagen synthesis. IFN-γ, was the only IFN that clearly inhibited α-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-β and IFN-γ, induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-α was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-γ. CONCLUSION： IFN-β and particularly IFN-γ, display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-γ action requires STAT1.

关键词： Interferons Pancreatic stellate cell Apoptosis

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Dynamics of lattice disorder in perovskite materials, polarization nanoclusters and ferroelectric domain wall structures

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npj Computational Materials 2023年第1期9卷 1137-1149页

作者： jan Očenášek ján Minár jorge Alcalá New Technologies Research Centre University of West Bohemia in Pilsen30614 PlzeňCzech Republic Department of Materials Science and Metallurgical Engineering InSupETSEIBUniversitat Politècnica de Catalunya08028 BarcelonaSpain

The nexus between classic ferroelectricity and the structure of perovskite materials hinges on the concept of lattice *** the ordered perovskites display short-range displacements of the central cations around their equilibrium points,the lattice disorder dynamically unfolds to generate a myriad of distorted rhombohedral lattices characterized by the hopping of the central cations across*** is discovered that the lattice disorder correlates with the emergence of minimum configuration energypathways for the central cations,resulting in spatially modulated ultrafast polarization nanocluster arrangements that are stabilized by the electric charge defects in the *** high-resolution phonon dispersion analyses encompassing molecular dynamics(MD)and density functional theory(DFT)simulations,we provide unequivocal evidence linking the hopping of central cations to the development of diffuse soft phonon modes observed throughout the phase transitions of the *** massive MD simulations,we unveil the impact of lattice disorder on the structures of domain walls at finite-temperature vis-à-vis collective activation and deactivation of***,our simulations demonstrate the development of hierarchical morphotropic phase boundary(MPB)nanostructures under the combined influence of externally applied pressure and stress relaxation,characterized by sudden emergence of zig-zagged monoclinic arrangements that involve dualshifts of the central *** findings have implications for tailoring MPBs in thin-film structures and for the light-induced mobilization of *** are finally uncovered to the exploration of lattice disorder through gradual shear strain application.

关键词： perovskite lattice ferroelectric

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