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Macrophage polarization in response to wear particles in vitro

Cellular & Molecular Immunology 2013年第6期10卷 471-482页

作者： joseph K Antonios Zhenyu Yao Chenguang Li Allison J Rao Stuart b Goodman Orthopaedic Research Laboratories Department of Orthopaedic Surgery Stanford University School of Medicine Stanford CA USA

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. while it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

关键词： IL-4 macrophage polarization osteolysis PMMA particles total joint replacement

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New Copper (II), Palladium (II), and Platinum (II) 2-Acetylpyrazine Tert-butylthiosemicarbazone Complexes: Inhibition of Human Topoisomerase IIα and Activity against breast Cancer Cells

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Open Journal of Medicinal Chemistry 2022年第1期12卷 1-13页

作者： Edward C. Lisic Sarah N. Grossarth Sarah b. bowman Jessica L. Hill Michael w. beck joseph E. Deweese Xiaohua Jiang Department of Chemistry Tennessee Technological University Cookeville TN USA Department of biological Physical and Human Sciences Freed Hardeman University Henderson TN USA

The new ligand, 2-acetylpyrazine-tertbutylthiosemicarbazone (APZ-tbTSC), and its Cu(II), Pd(II) and Pt(II) complexes have been synthesized. This ligand coordinates to the metal ions in a tridentate monoanionic fashion forming monometallic complexes with the formula [M(APZ-tbTSC)Cl]. The ligand and the three metal complexes [Cu(APZ-tbTSC)Cl], [Pd(APZ-tbTSC)Cl], and [Pt(APZ-tbTSC)Cl] were tested for anti-proliferative biological behavior with a panel of seven microbes, and the copper and palladium complexes were found to be highly active against Gram positive bacteria. The 4 compounds were also tested in human topoisomerase IIα DNA relaxation assays and all three metal complexes had topoisomerase inhibition at a concentration between 4 - 6 micro-molar. The 4 compounds were also tested for activity with the HEK293T cell line and also the breast cell cancer line, MDA-Mb-231. The most effective compound for activity against the HEK293T cell line was the [Cu(APZ-tbTSC)Cl] complex, and the MDA-Mb-231 breast cancer cell line was the [Pt(APZ-tbTSC)Cl] complex.

关键词： Topoisomerase breast Cancer α-(N)-Heterocyclic Thiosemicarbazones

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Inflammatory bowel diseases: From the mystical to the cellular and now the molecular

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world Journal of Gastroenterology 2005年第26期11卷 4127-4128页

作者： joseph b.Kirsner The Louis block Distinguished Service Professor of Medicine Department of Medicine-Section of Gastroenterology The University of Chicago IL 60637 United States

It is of interest in an era of increasing biomedical sophisticaton to recall that a relatively short time ago, early in the 20th century, ‘simple' ulcerative colitis was an obscure ‘medical curiosity' emerging slowly from an unknown past. Crohn's disease was yet unidentified as a separate entity although careful review of the IbD literature documented its early presence, masquerading as ‘intestinal tuberculosis'. Into the 1930s, the etiology and pathogenesis of ulcerative colitis and Crohn's disease were unknown, and investigative hypotheses were scarce. Therapeutic resources were limited and treatment was primitive. At a time of limited biomedical knowledge and minimal clinical awareness, unsubstantiated views prevailed, including ‘vague reactions to foods' (sugar,margarine, corn flakes), deficiency of a ‘protective factor'in pig intestine, and psychiatric disease.

关键词：炎性肠疾病细胞机制分子机制精神病学

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Deterministic Dual Control of Phase Competition in Strained biFeO_(3):A Multiparametric Structural Lithography Approach

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Nanomanufacturing and Metrology 2022年第1期5卷 60-66页

作者： Nathan black David Edwards Niall browne joseph G.M.Guy Niyorjyoti Sharma Kristina M・Holsgrove Aaron b.Naden Raymond G.P.McQuaid brian J.Rodriguez Amit Kumar School of Maths and Physics Queen's University BelfastBelfast BT7 INNUK School of Chemistry University of St.AndrewsSt Andrews KY169STUK School of Physics University College DublinBelfieldDublin 4Ireland

The realization of a mixed-phase microstructure in strained biFeO_(3)(bFO)thin films has led to numerous novel effects derived from the coexistence of the tetragonal-like monoclinic phase(T phase)and rhombohedral-like monoclinic phase(R phase).Strong strain and polarization diiferences between the phases should result in a high level of transformation plasticity,which enables the continuous alteration of the relative proportion of R and T states in response to external *** the potential for utilizing such plasticity to control mixed-phase populations under external stimuli is evident,direct experi・mental evidence backed by equilibrium predictions has not yet been fully *** we demonstrate deterministic control of mixed-phase populations in an epitaxially strained bFO thin film through the application of localized stresses and electric fields in a reversible manne匚The results illustrate and rationalize deterministic control of mixed phases in strained bFO films,which could be crucial in tuning their functional *** findings also highlight a new multiparametric technique in the scanning probe lithography toolbox based on tip-assisted electric and strain field manipulation of functional properties that might find application beyond the ferroelectric domain and structural phase lithography.

关键词： Phase competition Ferroelectric Stress Lithography

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Ultimate Strength Prediction of Carbon/Epoxy Tensile Specimens from Acoustic Emission Data

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Journal of Materials Science & Technology 2010年第8期26卷 725-729页

作者： V.Arumugam R.Naren Shankar b.T.N.Sridhar A.joseph Stanley Department of Aerospace Engineering Madras Institute of TechnologyAnna University

The objective of this paper was to predict the residual strength of post impacted carbon/epoxy composite laminates using an online acoustic emission （AE） monitoring and artificial neural networks （ANN）. The laminates were made from eight-layered carbon （in woven mat form） with epoxy as the binding medium by hand lay-up technique and cured at a pressure of 100 kg/cm2 under room temperature using a 30 ton capacity compression molding machine for 24 h. 21 tensile specimens （ASTM D3039 standard） were cut from the cross ply laminates. 16 specimens were subjected to impact load from three different heights using a Fractovis Plus drop impact tester. both impacted and non-impacted specimens were subjected to uniaxial tension under the acoustic emission monitoring using a 100 kN FIE servo hydraulic universal testing machine. The dominant AE parameters such as counts, energy, duration, rise time and amplitude are recorded during monitoring. Cumulative counts corresponding to the amplitude ranges obtained during the tensile testing are used to train the network. This network can be used to predict the failure load of a similar specimen subjected to uniaxial tension under acoustic emission monitoring for certain percentage of the average failure load.

关键词： Acoustic emission (AE) Carbon/epoxy laminate Tensile testing Artificial neuralnetworks

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Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

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Frontiers of Medicine 2015年第3期9卷 288-303页

作者： joseph Cannova biochemistry and Molecular biology Program Loyola University Chicago Maywood IL 60153 USA Stritch School of Medicine Loyo& University Chicago Maywood IL 60153 USA Oncology Institute Loyola University Chicago Maywood IL 60153 USA Department of Pathology Loyola University Chicago Maywood IL 60153 USA Department of biology Loyola University Chicago Chicago IL 60660 USA Department of Molecular and Cellular Physiology Loyola University Chicago Maywood IL 60153 USA

Toll-like receptors （TLRs）, which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in b-cell lymphomas and other b-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

关键词： TLR MyD88 hematopoiesis bone marrow failure leukemia myelodysplastic syndrome

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Modeling some long-term implications of CO_2 fertilization for global forests and forest industries

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Forest Ecosystems 2016年第1期3卷 13-25页

作者： joseph buongiorno Department of Forest and wildlife Ecology University of Wisconsin-Madison

background： This paper explored the long-term, ceteris-paribus effects of potential CO2 fertilization on the global forest sector. based on the findings of Norby et al. （PNAS 2005, 102（50）） about forest response to elevated [CO2]. Methods： Forest productivity was increased in the Global Forest Products Model （GFPM） in proportion to the rising [CO2] projected in the IPCC scenario A1b, A2, and 132. Projections of the forest area and forest stock and of the production, consumption, prices, and trade of products ranging from fuelwood to paper and paperboard were obtained with the GFPM for each scenario, with and without CO2 fertilization beginning in 2011 and up to 2065. Results： CO2 fertilization increased wood supply, leading to lower wood prices which in turn induced modest lower prices of end products and higher global consumption. However, production and value added in industries decreased in some regions due to the relative competitive advantages and to the varying regional effects of CO2 fertilization. Conclusion： The main effect of CO2 fertilization was to raise the level of the world forest stock in 2065 by 9 to 10 % for scenarios A2 and b2 and by 20 % for scenario A1b. The rise in forest stock induced by fertilization was in part counteracted by its stimulation of the wood supply which resulted in lower wood prices and increased harvests.

关键词： CO2 fertilization Climate change Prices Supply Demand International trade

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Resection of hepatitis b virus-related hepatocellular carcinoma:Evolving strategies and emerging therapies to improve outcome

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world Journal of Gastroenterology 2014年第35期20卷 12473-12484页

作者： gar-Yang Chau Division of General Surgery Department of SurgeryTaipei Veterans General Hospitaland School of MedicineNational Yang-Ming University

The incidence of hepatocellular carcinoma(HCC) is increasing worldwide,largely due to hepatitis b virus(HbV),hepatitis C virus and liver *** HbV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian *** resection is currently the mainstay of treatment due to the low surgical mortality,a wider treatment indication,and simplicity of post-treatment *** is an ever-increasing demand on surgeons to perform curative liver resection in HCC,with the hope of avoiding tumor *** b-related-HCC has distinct clinicopathological features,which should be considered when treating the *** author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome,with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.

关键词： Hepatocellular carcinoma Hepatitis b virus Hepatic

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Treatment of Nonalcoholic Fatty Liver Disease: The Role of Medical, Surgical, and Endoscopic weight Loss

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Journal of Clinical and Translational Hepatology 2015年第3期3卷 230-238页

作者： Violeta b.Popov joseph K.Lim Division of Gastroenterology New York University School of Medicine New York NY USA Yale Liver Center Section of Digestive Diseases Yale University School of Medicine New Haven CT USA

Nonalcoholic fatty liver disease (NAFLD) represents a rapidly growing cause of chronic liver disease in the United States and is associated with significant morbidity and mortality,including progression to liver cirrhosis and hepatocellular *** comprises a spectrum of liver conditions,ranging from simple steatosis to steatosis with inflammation (steatohepatitis) and progressive *** loss represents a first line therapeutic modality for the management of ***,we review the evidence base for medical,surgical,and endoscopic approaches to weight loss and their potential impact on the natural history of NAFLD.

关键词： Fatty liver Nonalcoholic steatohepatitis weight loss Exercise Pharmacotherapy Endoscopic therapy bariatric surgery

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FAIR Machine Learning Model Pipeline Implementation of COVID-19 Data

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Data Intelligence 2022年第4期4卷 971-990,1036页

作者： Sakinat Folorunso Ezekiel Ogundepo Mariam basajja joseph Awotunde Abdullahi Kawu Francisca Oladipo Abdullahi Ibrahim Department of Mathematical Sciences Olabisi Onabanjo UniversityP.M.B 2002Ago-IwoyeOgun StateNigeria 120005Nigeria Data Science Nigeria Lagos 105102Nigeria Leiden University 1011NCAmsterdamthe Netherlands Department of Computer Science University of IlorinIlorinKwara State240103Nigeria Department of Computer Science Ibrahim Badamosi UniversityLapaiNiger State911101Nigeria Kampala International University 260101Uganda Federal University Lokoja Nigeria Virus Outbreak Data Network-Africa

Research and development are gradually becoming data-driven and the implementation of the FAIR Guidelines(that data should be Findable, Accessible, Interoperable, and Reusable) for scientific data administration and stewardship has the potential to remarkably enhance the framework for the reuse of research data. In this way, FAIR is aiding digital transformation. The ‘FAIRification’ of data increases the interoperability and(re)usability of data, so that new and robust analytical tools, such as machine learning(ML) models, can access the data to deduce meaningful insights, extract actionable information, and identify hidden patterns. This article aims to build a FAIR ML model pipeline using the generic FAIRification workflow to make the whole ML analytics process FAIR. Accordingly, FAIR input data was modelled using a FAIR ML model. The output data from the FAIR ML model was also made FAIR. For this, a hybrid hierarchical k-means (HHK) clustering ML algorithm was applied to group the data into homogeneous subgroups and ascertain the underlying structure of the data using a Nigerian-based FAIR dataset that contains data on economic factors, healthcare facilities, and coronavirus occurrences in all the 36 states of Nigeria. The model showed that research data and the ML pipeline can be FAIRified, shared, and reused by following the proposed FAIRification workflow and implementing technical architecture.

关键词： FAIRification Semantic data model Cluster analysis FAIR data Metadata Machine learning model

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