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World Journal of Gastroenterology 2015年第5期21卷 1436-1443页

作者： jean-noel freund Isabelle Duluc jean-Marie Reimund Isabelle Gross Claire Domon-Dell INSERM UMR_S1113 Université de StrasbourgFMTS67200 StrasbourgFrance Centre Hospitalier Universitaire de Strasbourg 67200 StrasbourgFrance

The homeoprotein encoded by the intestinal-specific Cdx2 gene is a major regulator of gut development and homeostasis,also involved in colon cancer as well as in intestinal-type metaplasias when it is abnormally expressed outside the gut.At the molecular level,structure/function studies have demonstrated that the Cdx2 protein is a transcription factor containing a conserved homeotic DNA-binding domain made ofthree alpha helixes arranged in a helix-turn-helix motif,preceded by a transcriptional domain and followed by a regulatory domain.The protein interacts with several thousand sites on the chromatin and widely regulates intestinal functions in stem/progenitor cells as well as in mature differentiated cells.Yet,this transcription factor also acts trough original nontranscriptional mechanisms.Indeed,the identification of novel protein partners of Cdx2 and also of a splicing variant revealed unexpected functions in the control of signaling pathways like the Wnt and NF-k B pathways,in double-strand break DNA repair and in premessenger RNA splicing.These novel functions of Cdx2 must be considered to fully understand the complexity of the role of Cdx2 in the healthy intestine and in diseases.

关键词： Homeobox Transcription Signaling DNA repair RNA splicing Intestine Development Cancer Homeostasis

Inflammatory bowel disease in rats:Bacterial and chemical interaction

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World Journal of Gastroenterology 2008年第25期14卷 4028-4039页

作者： Inaya Abdallah Hajj Hussein Rania Tohme Kassem Barada Mostafa Hassan Mostafa jean-noel freund Rosalyn A Jurjus Walid Karam Abdo Jurjus Faculty of Medicine 110236/41 Riad El-Slaleh 1107-2020 American University of Beirut Faculty of Science 115020 Beirut Arab University INSERM 682 Ontogenese et pathologie du system digestif Strasbourg France Institut National De Pathologie Beirut Lebanon

AIM: To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 μL of 6% iodoacetamide (IA) in 1% MC, (c) 200 μL containing 4 × 108 colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-α gene expression. RESULTS: Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA conti-nued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological altera- tions characteristic of UC, with an extensive inflamma- tory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals. CONCLUSION: The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.

关键词：炎症肠疾病临床表现碘乙酰胺化学治疗

Challenges in the conduct of randomised controlled trials in cardiogenic shock complicating acute myocardial infarction

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Journal of Geriatric Cardiology 2022年第2期19卷 125-129页

作者： Anne freund Steffen Desch Holger Thiele Department of Internal Medicine/Cardiology Heart Center Leipzig at the University of LeipzigLeipzigGermany German Center for Cardiovascular Research(DZHK) BerlinDeutschland

Cardiogenic shock(CS)following acute myocardial infarction(AMI)is a major challenge in cardiovascular care.Mortality remains high with 40%-50%after thirty days.Randomised controlled trials(RCTs)play a key role to generate evidence on optimal care in this field.However,the number of completed or ongoing RCTs is still relatively low compared to the gaps in evidence.Challenges in the conduct of these trials are in particular the selection of patients and ethical issues in the informed consent process.When determining eligibility criteria,special attention should be paid to the severity of CS,to the inclusion of patients with cardiac arrest and to potential age limits.Median age of AMI-CS patients is increasing.Age limits are therefore controversial as it is important to include elderly patients in RCTs in order to make the results generalisable and to address the special needs of this group.As patients with AMI-CS are in most cases unable to provide informed consent themselves,a step-wise approach with acute consent by a legal representative or independent physicians and later informed consent by the patient if possible might be established depending on regularities of the respective ethical review board and country legislation.Multicenter studies should be sought to generate adequate power.

关键词： shock legal consent

Effect of patient COVID-19 vaccine hesitancy on hospital care team perceptions

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World Journal of Clinical Cases 2023年第4期11卷 821-829页

作者： Inbar Caspi Ophir freund Omer Pines Odelia Elkana Jacob N Ablin Gil Bornstein Internal Medicine Department B Tel-Aviv Sourasky Medical Center and Sackler Faculty of MedicineTel Aviv UniversityTel Aviv 6423906Israel Behavioral Sciences Department Academic College of Tel Aviv-YaffoTel Aviv 6818211Israel Internal Medicine Department H Tel Aviv Sourasky Medical Center and Sackler School of MedicineTel Aviv 6423906Israel

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic posed new challenges in patient care worldwide.Vaccinations,which have proven efficacious in lowering the COVID-19 hospital burden,are still avoided by large populations.We,therefore,hypothesized that hospital care teams would have worse perceptions regarding the characteristics and care of patients with vaccine hesitancy.AIM To evaluate whether patient vaccine hesitancy affected the hospital care team(HCT)perceptions.METHODS We performed a prospective clinical study using structured questionnaires.We approached physicians and nurses with previous experience caring for COVID-19patients from 11 medical centers across Israel during the fourth COVID-19 surge(September and October 2021).The participants completed a questionnaire with the following parts:(1)Sociodemographic characteristics;(2)Assessment of anger(STAXI instrument)and chronic workplace stress(Shirom-Melamed burnout measure);and(3)Three tools to assess the effect of patient vaccine hesitancy on the HCT perceptions(the difficult doctor-patient relation questionnaire,the medical staff perception of patient’s responsibility questionnaire and the characterological derogation questionnaire).Results were evaluated according to each part of the questionnaire and the questionnaire as a whole.Associations between HCT perceptions and their baseline characteristics,anger or chronic workplace stress were assessed.RESULTS The HCT experienced their relationship with unvaccinated patients as more difficult(P<0.001,Cohen’s d=0.85),perceived unvaccinated patients as responsible for their medical condition(P<0.001,d=1.39)and perceived vaccinated patients as having a higher character value(P<0.001,d=1.03).Unvaccinated patients were considered selfish(P<0.001),less mature(P<0.001)and less satisfying to care for(P<0.001).The relationship with unvaccinated patients was more difficult among HCT with higher burnout(r=0.37,n=66,P=0.002).No correlations with baseline characteristics were found.All three study tools showed

关键词： COVID-19 Vaccination Hesitancy Patient care Doctor-patient relationship Attitudes

Metabolic signatures of Arabidopsis thaliana abiotic stress responses elucidate patterns in stress priming,acclimation,and recovery

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Stress Biology 2022年第1期2卷 550-565页

作者： Yuan Xu Dana M.freund Adrian D.Hegeman Jerry D.Cohen Department of Horticultural Science and the Microbial and Plant Genomics Institute University of MinnesotaMNSaint PaulUSA Department of Plant and Microbial Biology University of MinnesotaMNSaint PaulUSA

Temperature,water,and light are three abiotic stress factors that have major influences on plant growth,development,and reproduction.Plants can be primed by a prior mild stress to enhance their resistance to future stress.We used an untargeted metabolomics approach to examine Arabidopsis thaliana 11-day-old seedling’s abiotic stress responses including heat(with and without priming),cold(with and without priming),water-deficit and high-light before and after a 2-day-recovery period.Analysis of the physiological phenotypes showed that seedlings with stress treatment resulted in a reduction in fresh weight,hypocotyl and root length but remained viable.Several stress responsive metabolites were identified,confirmed with reference standards,quantified,and clustered.We identified shared and specific stress signatures for cold,heat,water-deficit,and high-light treatments.Central metabolism including amino acid metabolism,sugar metabolism,glycolysis,TCA cycle,GABA shunt,glutathione metabolism,purine metabolism,and urea cycle were found to undergo changes that are fundamentally different,although some shared commonalities in response to different treatments.Large increases in cysteine abundance and decreases in reduced glutathione were observed following multiple stress treatments highlighting the importance of oxidative stress as a general phenomenon in abiotic stress.Large fold increases in low-turnover amino acids and maltose demonstrate the critical role of protein and starch autolysis in early abiotic stress responses.

关键词： Abiotic stress Arabidopsis thaliana LC-HRMS Metabolomics Plant stress acclimation Priming Recovery

Quantitative relationship between surface sedimentary diatoms and water depth in North-Central Bohai Bay,China

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China Geology 2023年第1期6卷 61-69页

作者： Zhi-wen Shang Jian-fen Li Holger freund Pei-xin Shi Hong Wang Tianjin Centre China Geological SurveyMinistry of Natural ResourcesTianjin 300170China Key Laboratory of Coast Geo-environment China Geological SurveyMinistry of Natural ResourcesTianjin 300170China Institute of Chemistry and Biology of the Marine Environment Carl von Ossietzky University of OldenburgOldenburg 26111Germany

To study the quantitative relationship between surface sedimentary diatoms and water depth,67 surface samples were collected for diatom analysis on eight profiles with water depth variation from the muddy intertidal zone to the shallow sea area in North-Central Bohai Bay,China.The results showed that the distribution of diatoms changed significantly in response to the change in water depth.Furthermore,the quantitative relationship between the distribution of dominant diatom species,their assemblages,and the water depth was established.The water depth optima for seven dominant species such as Cyclotella striata/stylorum,Paralia sulcata,and Coscinodiscus perforatus and the water depth indication range of seven diatom assemblages were obtained in the study area above the water depth(elevation)of-10 m.The quantitative relationship between surface sedimentary diatoms and water depth provides a proxy index for diatom-paleo-water depth reconstruction in the strata in Bohai Bay,China.

关键词： Diatom Surficial sediments Water depth(elevation) Quantitative relationship Sea level change Paleo-environment change Marine geological survey engineering North-central Bohai Bay China

EVOLUTION OF ROUGHNESS ON THE SURFACE OF A STRAINED ELASTIC MATERIAL DUE TO STRESS-DRIVEN SURFACE DIFFUSION

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Acta Mechanica Sinica 1994年第1期10卷 16-26页

作者： L.B.freund Division of Engineering Brown University Providence RI 02912 USA

The free energy of a stressed crystal is assumed to consist of elastic strain energy and surface energy, and the chemical potential for surface diffusion at constant temperature is obtained under this assumption. A gradient in chemical potential results in diffusive mass transport along the surface. The result is applied in considering the phenomena of instability of a flat surface in a stressed material under fluctuations in surface shape, and the transient evolution of surface roughness due to an initial perturbation in the nearly flat free surface of the material, both under plane strain conditions.

关键词： elastic material surface energy diffusion

Forced motion of an elastic filament through a narrow tube

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Acta Mechanica Sinica 2015年第6期31卷 789-790页

作者： L.B.freund Department of Materials Science and Engineering University of Illinois at Urbana Champaign

A polymer filament consisting of many similar molecules linked in a one-dimensional array is very flexible. As a result, shapes with a relatively large curvature can be accommodated elastically. When loosely confined in a thermal environment, such a flexible strand may become tangled owing to its flexibility. When confined within a narrow ＂tube＂ over its full length, a flexible molecule may behave quite differently. Here, we consider the qualitative nature of deformation of an individual filament when confined within a tube. Commonly the tube is formed within the cluster by a large number of surrounding filaments of the same type.

关键词： Statistical mechanics. Biofilament. Reptation,Partition function

How a membrane agent buys goods in a membrane store

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Progress in Natural Science:Materials International 2007年第4期17卷 442-448页

作者： Rudolf freund Marion Oswald Thomas Schirk Institute of Computer Languages Vienna University of Technology Favoritenstr. 9 WienAustria

In this paper we consider a specific model of membrane systems, i. e. membrane systems with attributes. In these systems, the information is placed at the membranes in form of attributes, no objects are considered inside the membranes except for other membranes. The membrane system with attributes evolves according to rules that compute new values for the attributes from the attributes assigned to the membranes involved in the rule. The model of membrane systems with attributes allows us to specify business transactions in a precise way and to simulate different models for such transactions with a suitable tool for membrane systems with attributes.

关键词： model membrane systems with attributes.

Fluctuation pressure on a bio-membrane confined within a parabolic potential well

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Acta Mechanica Sinica 2012年第4期28卷 1180-1185页

作者： L. B. freund Department of Materials Science and Engineering University of Illinois at Urbana-Champaign

A compliant bio-membrane with a nominally fiat reference configuration is prone to random transverse deflections when placed in water, due primarily to the Brownian motion of the water molecules. On the average, these fluctuations result in a state of thermodynamic equilibrium between the entropic energy of the water and the total free en- ergy of the membrane. When the membrane is in close proximity to a parallel surface, that surface restricts the fluctuations of the membrane which, in turn, results in an increase in its free energy. The amount of that increase depends on the degree of confinement, and the resulting gradient in free energy with degree of confinement implies the existence of a confining pressure. In the present study, we assume that the confinement is in the form of a continuous parabolic po- tential well resisting fluctuation. Analysis leads to a closed form expression for the mean pressure resulting from this confinement, and the results are discussed within the broader context of results in this area. In particular, the results provide insights into the roles of membrane stiffness, number of degrees of freedom in the model of the membrane and other system parameters.

关键词： Statistical mechanics ＇ Membrane fluctuations Parabolic confinement. Confining pressure