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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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Learning to become addicted,one synapse at a time

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Neural Regeneration Research 2024年第2期19卷 401-402页

作者： Alessio Attardo Sidney B.Cambridge Leibniz Institute for Neurobiology MagdeburgGermany Institute for Anatomy II Dr.Senckenberg AnatomyGoethe-University Frankfurt am MainFrankfurtGermany

Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli ... 详细信息

关键词： clinical therapy

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Litter production and leaf nutrient concentration and remobilization in response to climate seasonality in the central amazon

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Journal of Forestry Research 2024年第3期35卷 131-141页

作者： Ricardo Antonio Marenco Saul Alfredo Antezana-Vera Daniela Pereira Dias Luiz Antonio Candido Instituto Nacional de Pesquisas da amazonia Coordenagao de Uso da Terra e Mudanca ClimaticaAv.Andre Araujo 2936ManausAM69067-375Brazil Programa de pos-Graduagao em Agricultura no Tropico Umido Instituto Nacional de Pesquisas da Amazonia-INPAManausAMBrazil Unidade Academica de Ciencias Agrarias Universidade Federal de JataiBR 364km 195JataiGO 75801-615Brazil

Litterfall is the largest source of nutrients to for-est soils of tropical ***,variability in lit-terfall production,nutrient remobilization,and changes in leaf nutrient concentration with climate seasonality remain largely unknown for the central *** study meas-ured litterfall production,leaf nutrient remobilization,and leaf area index on a forest plateau in the central *** was measured at monthly intervals during 2014,while nitrogen,phosphorus,potassium,calcium and mag-nesium concentrations of leaf litter and canopy leaves were measured in the dry and rainy seasons,and remobilization rates *** area index was also recorded in the dry and rainy *** litterfall varied from 33.2(in the rainy season)to 87.6 g m^(-2) in the dry season,while leaf area index increased slightly in the rainy *** seasonality had no effect on concentrations of nitrogen,calcium,and magnesium,whereas phosphorous and potassium responded to rainfall seasonality *** phosphorous increased,potassium decreased during the dry *** seasons,nitrogen,potassium,and phosphorous decreased in leaf litter;calcium increased in leaf litter,while magnesium remained unaffected with leaf ***,the five nutrients had similar remobilization rates over the *** absence of climate seasonality on nutrient remobilization suggests that the current length of the dry season does not alter nutrient remobilization rates but this may change as dry periods become more prolonged in the future due to climate change.

关键词： Throughfall Nutrient cycling Climatic seasonality Leaf mass per area

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Temperature and structure measurements of heavy-ion-heated diamond using in situ X-ray diagnostics

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Matter and Radiation at Extremes 2024年第4期9卷 80-89页

作者： J.Lutgert P.Hesselbach M.Schorner V.Bagnoud R.Belikov P.Drechsel B.Heuser O.SHumphries P.Katrik B.Lindqvist C.Qu R.Redmer D.Riley G.Schaumann S.Schumacher A.Tauschwitz D.Varentsov K.Weyrich X.Yu B.Zielbauer Zs.Major P.Neumayer D.Kraus Institut fur Physik Universitat RostockAlbert-Einstein-Str.2318059 RostockGermany GSI Helmholtzzentrum fur Schwerionenforschung Planckstr.164291 DarmstadtGermany Institut für Angewandte Physik Goethe-Universität Frankfurt am MainMax-von-Laue-Str.160438 Frankfurt am MainGermany Institut fur Geowissenschaften Goethe-Universitat Frankfurt am MainAltenhoferallee 160438 Frankfurt am MainGermany Helmholtz-Zentrum Dresden-Rossendorf Bautzner Landstr.40001328 DresdenGermany European XFEL GmbH Holzkoppel 422869 SchenefeldGermany Centre for Plasma Physics School of Mathematics and PhysicsQueen’s University BelfastUniversity RoadBelfast BT71NNUnited Kingdom Institut für Kernphysik Technische Universität DarmstadtSchlossgartenstr.964289 DarmstadtGermany State Key Laboratory of Nuclear Physics and Technology Institute of Heavy Ion PhysicsPeking UniversityBeijing 100871China Helmholtz Institut Jena Frobelstieg 307743 JenaGermany

We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heatedwith an intense pulse of heavy *** this way,we determine the samples’heating dynamics and their microscopic and macroscopic structuralintegrity over a timespan of several *** the ratio of elastic to inelastic scattering with state-of-the-art density functionaltheory molecular dynamics simulations allows the inference of average temperatures around 1300 K,in agreement with predictions fromstopping power *** simultaneous diffraction measurements show no hints of any volumetric graphitization of the material,butdo indicate the onset of fracture in the diamond *** experiments pave the way for future studies at the Facility for Antiproton andIon Research,where a substantially increased intensity of the heavy ion beam will be available.

关键词： heated intense structure

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Snapshot imaging of ultrashort electron bunches

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Light(Science & Applications) 2024年第7期13卷 1226-1228页

作者： Andreas Döpp Ludwig-Maximilian-Universität München Am Coulombwall 185748GarchingGermany Max Planck Institut für Quantenoptik Hans-Kopfermann-Strasse 1Garching85748Germany

New measurements combine spatial and temporal information from optical transition radiation to estimate the three-dimensional structure of electron bunches from a laser wakefield accelerator.

关键词： ultrashort Snapshot electron

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Experimental and numerical investigation on alternatives to sandy gravel

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Defence Technology（防务技术） 2024年第1期31卷 130-141页

作者： V.Denefeld H.Aurich Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institut(EMI)Ernst-Zermelo-Str.479104FreiburgGermany Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institut(EMI)Am Christianswuhr 279400KandernGermany

The NATO agreement STANAG 4569 defines the protection levels for the occupants of logistic and light armored *** Allied Engineering Publication,AEP-55,Volume 2 document outlines the test conditions for underbelly improvised explosive device(IEDs),which must be buried in water-saturated sandy *** use of sandy gravel has some drawbacks,for instance reproducibility,time consumption,and *** paper focuses on the investigation of four alternatives to sandy gravel,which could produce similar specific and cumulative impulses:a concrete pot filled with water,a concrete pot filled with quartz sand,a steel pot without filling and a concrete pot filled with glass spheres(diameter 200μm—300μm)and different water *** impulses are measured with a ring technology developed at the Fraunhofer EMI.A numerical soil model based on the work of Marrs,2014 and Fi serov a,2006 and considering the soil moisture was used to simulate the experiments with glass spheres at different water contents,showing much better agreement with the experiments than the classical Laine&Sandvik model,even for high saturation *** results can be used to create new test conditions at original scale that are more cost-effective,more reproducible and simpler to manage in comparison to the current tests carried out with STANAG sandy gravel.

关键词： Improvised explosive device(IED) Specific impulse Momentum transfer Sandy gravel Glass spheres Numerical model Soil moisture

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RUSAS: Roman Urdu Sentiment Analysis System

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Computers, Materials & Continua 2024年第4期79卷 1463-1480页

作者： Kazim Jawad Muhammad Ahmad Majdah Alvi Muhammad Bux Alvi Faculty of Computer Science and Engineering Frankfurt University of Applied SciencesFrankfurt am Main60318Germany Technical Writer and Researcher Proteus Technologies LLCIslamabad04405Pakistan Faculty of Engineering The Islamia University of BahawalpurBahawalpur63100Pakistan

Sentiment analysis, the meta field of Natural Language Processing (NLP), attempts to analyze and identify thesentiments in the opinionated text data. People share their judgments, reactions, and feedback on the internetusing various languages. Urdu is one of them, and it is frequently used worldwide. Urdu-speaking people prefer tocommunicate on social media in Roman Urdu (RU), an English scripting style with the Urdu language *** have developed versatile lexical resources for features-rich comprehensive languages, but limitedlinguistic resources are available to facilitate the sentiment classification of Roman Urdu. This effort encompassesextracting subjective expressions in Roman Urdu and determining the implied opinionated text polarity. Theprimary sources of the dataset are Daraz (an e-commerce platform), Google Maps, and the manual effort. Thecontributions of this study include a Bilingual Roman Urdu Language Detector (BRULD) and a Roman UrduSpelling Checker (RUSC). These integrated modules accept the user input, detect the text language, correct thespellings, categorize the sentiments, and return the input sentence’s orientation with a sentiment intensity *** developed system gains strength with each input experience gradually. The results show that the languagedetector gives an accuracy of 97.1% on a close domain dataset, with an overall sentiment classification accuracy of94.3%.

关键词： Roman Urdu sentiment analysis Roman Urdu language detector Roman Urdu spelling checker flask

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Two-photon emission from a superlattice-based superconducting light-emitting structure

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Light(Science & Applications) 2024年第7期13卷 1331-1340页

作者： Shlomi Bouscher Dmitry Panna Ronen Jacovi Fauzia Jabeen Christian Schneider Sven Höfling Alex Hayat Department of Electrical Engineering TechnionHaifa 32000Israel. Technische Physik Universität WürzburgAm HublandD-97074 WürzburgGermany. Institute of Physics Carl von Ossietzky Universität OldenburgD-26111 OldenburgGermany

Superconductor-semiconductor hybrid devices can bridge the gap between solid-state-based and photonics-based quantum systems,enabling new hybrid computing schemes,offering increased scalability and *** example for a hybrid device is the superconducting light-emitting diode(SLED).SLEDs have been theoretically shown to emit polarization-entangled photon pairs by utilizing radiative recombination of Cooper ***,the twophoton nature of the emission has not been shown experimentally *** demonstrate two-photon emission in a GaAs/AlGaAs *** electroluminescence spectra reveal unique two-photon superconducting features below the critical temperature(Tc),while temperature-dependent photon-pair correlation experiments(g(2)(τ,T))demonstrate temperature-dependent time coincidences below Tc between photons emitted from the *** results pave the way for compact and efficient superconducting quantum light sources and open new directions in light-matter interaction studies.

关键词： photon quantum utilizing

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Revisiting the stretch-induced force deficit:A systematic review with multilevel meta-analysis of acute effects

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Journal of Sport and Health Science 2024年第6期13卷 805-819页

作者： Konstantin Warneke Lars Hubertus Lohmann Institute of Human Movement Science Sport and HealthUniversity of GrazGraz 8010Austria Institute of Sport Science Alpen-Adria University of KlagenfurtKlagenfurt am Worthersee 9020Austria Institute of Human Movement and Exercise Physiology University of JenaJena 07749Germany

Background:When recommending avoidance of static stretching prior to athletic performance,authors and practitioners commonly refer to available systematic ***,effect sizes(ES)in previous reviews were extracted in major part from studies lacking control conditions and/or prepost testing ***,currently available reviews conducted calculations without accounting for multiple study outcomes,with ES:0.03 to 0.10,which would commonly be classified as ***:Since new meta-analytical software and controlled research articles have appeared since 2013,we revisited the available literatures and performed a multilevel meta-analysis using robust variance estimation of controlled prepost trials to provide updated ***,previous research described reduced electromyography activity—also attributable to fatiguing training routines—as being responsible for decreased subsequent *** second part of this study opposed stretching and alternative interventions sufficient to induce general fatigue to examine whether static stretching induces higher performance losses compared to other exercise ***:Including 83 studies with more than 400 ES from 2012 participants,our results indicate a significant,small ES for a static stretch-induced maximal strength loss(ES=0.21,p=0.003),with high magnitude ES(ES=0.84,p=0.004)for stretching durations≥60 s per bout when compared to passive *** opposed to active controls,the maximal strength loss ranges between ES:0.17 to0.28,p<0.001 and 0.040 with mostly no to small ***,stretching did not negatively influence athletic performance in general(when compared to both passive and active controls);in fact,a positive effect on subsequent jumping performance(ES=0.15,p=0.006)was found in ***:Regarding strength testing of isolated muscles(e.g.,leg extensions or calf raises),our results confirm previous ***,since no(or even positive)e

关键词： Static stretching Maximal strength Athletic performance Performance testing

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Defense and anti-defense mechanisms of bacteria and bacteriophages

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 181-196页

作者： Xiaoqing WANG Sebastian LEPTIHN School of Medicine Lishui UniversityLishui 323000China University of Edinburgh Medical School Biomedical SciencesCollege of Medicine&Veterinary MedicineThe University of EdinburghEdinburgh EH89JZUK HMU Health and Medical University Am Anger 64/73-99084 ErfurtGermany

In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by *** use of bacteriophages is a promising alternative to treat infections,supplementing or possibly even replacing *** phages for therapy is possible,since these bacterial viruses can kill bacteria specifically,causing no harm to the normal ***,bacteria have developed a multitude of sophisticated and complex ways to resist infection by phages,including abortive infection and the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated(Cas)*** also can evolve and acquire new anti-defense strategies to continue *** in-depth exploration of both defense and anti-defense mechanisms would contribute to optimizing phage therapy,while we would also gain novel insights into the microbial *** this paper,we summarize recent research on bacterial phage resistance and phage anti-defense mechanisms,as well as collaborative win-win systems involving both virus and host.

关键词： Bacteriophage Phage resistance Abortive infection Phage therapy

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