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Current perspectives and the future of disease-modifying therapies in type 1 diabetes

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World Journal of Diabetes 2025年第1期16卷 12-21页

作者： Sunetra Mondal joseph M Pappachan Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Department of Endocrinology Kasturba Medical CollegeManipal 576104India

Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for *** include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or *** is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target *** and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of *** benefits have been apparent as early as six months to as long as seven years after *** has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of *** their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety ***,all the included randomized control trials have been conducted in high-income *** cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.

关键词： Teplizumab Type 1 diabetes mellitus Disease modifying therapy β-cell function C-peptide Immunotherapy

Influence of surface modified mixed metal oxide nanoparticles on the electrochemical and mechanical properties of polyurethane matrix

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Frontiers of Chemical Science and Engineering 2023年第1期17卷 1-14页

作者： joseph Raj Xavier Department of Chemistry Saveetha School of EngineeringSaveetha Institute of Medical and Technical SciencesChennai-602105India

Newly synthesized functional nanoparticles,3-amino-1,2,4-triazole(ATA)/SiO_(2)—TiO_(2)were introduced to the polyurethane(PU)*** techniques were used to investigate the barrier properties of the synthesized PU—ATA/SiO_(2)—TiO_(2)nanocomposite coated steel *** natural seawater,electrochemical impedance spectroscopy experiments indicated outstanding protective behaviour for the PU—ATA/SiO_(2)—TiO_(2)coated *** coating resistance(Rcoat)of PU—ATA/SiO_(2)—TiO_(2)was determined to be 2956.90 kΩ·cm^(−2).The Rcoat of the PU—ATA/SiO_(2)—TiO_(2)nanocomposite coating was found to be over 50%higher than the PU *** current measured along the scratched surface of the PU—ATA/SiO_(2)—TiO_(2)coating was found to be very low(1.65 nA).The enhanced ATA/SiO_(2)—TiO_(2)nanoparticles inhibited the entry of electrolytes into the coating interface,as revealed by scanning electron microscopy/energy dispersive X-ray spectroscopy and X-ray diffraction analysis of the degradation *** contact angle testing validated the hydrophobic nature of the PU—ATA/SiO_(2)—TiO_(2)coating(θ=115.4°).When the concentration of ATA/SiO_(2)—TiO_(2)nanoparticles was 2 wt%,dynamic mechanical analysis revealed better mechanical ***,the newly synthesised PU—ATA/SiO_(2)—TiO_(2)nanocomposite provided excellent barrier and mechanical properties due to the addition of ATA/SiO_(2)—TiO_(2)nanoparticles to the polyurethane,which inhibited material degradation and aided in the prolongation of the coated steel’s life.

关键词： SiO_(2)/TiO_(2)nanoparticle nanocomposite coatings dynamic mechanical analysis electrochemical techniques corrosion colloids and interfaces

On Two Classes of Finite Inseparable p-Groups

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Acta Mathematica Sinica,English Series 2015年第7期31卷 1203-1214页

作者： joseph KIRTL Department of Mathematics Marist College

A finite group is inseparable, it does not split over any proper nontrivial normal subgroup; that is, if it has no nontrivial semidirect product decompositions. This paper investigates two classes of finite inseparabl... 详细信息

关键词： p-group inseparable splitting

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

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

Nonlinearly Coupled KdV Equations Describing the Interaction of Equatorial and Midlatitude Rossby Waves

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Chinese Annals of Mathematics,Series B 2009年第5期30卷 483-504页

作者： joseph A. BIELLO Department of Mathematics University of California at Davis

Amplitude equations governing the nonlinear resonant interaction of equatorial baroclinic and barotropic Rossby waves were derived by Majda and Biello and used as a model for long range interactions （teleconnections） between the tropical and midlatitude troposphere. An overview of that derivation is nonlinear wave theory, but not in atmospheric presented and geared to readers versed in sciences. In the course of the derivation, two other sets of asymptotic equations are presented： the long equatorial wave equations and the weakly nonlinear, long equatorial wave equations. A linear transformation recasts the amplitude equations as nonlinear and linearly coupled KdV equations governing the amplitude of two types of modes, each of which consists of a coupled tropical/midlatitude flow. In the limit of Rossby waves with equal dispersion, the transformed amplitude equations become two KdV equations coupled only through nonlinear fluxes. Four numerical integrations are presented which show （i） the interaction of two solitons, one from either mode, （ii） and （iii） the interaction of a soliton in the presence of different mean wind shears, and （iv） the interaction of two solitons mediated by the presence of a mean wind shear.

关键词： Coupled KdV equations Equatorial Rossby waves Solitary waves Atmospheric teleconnections

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats

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World Journal of Gastroenterology 2010年第7期16卷 837-845页

作者： joseph JY Sung Faculty of Medicine The Chinese University of Hong Kong

AIM:To investigate the pharmacological effect of JCM-16021,a Chinese herbal formula,and its underlying ***:JCM-16021 is composed of seven herbal plant *** raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia(2005).In a neonatal maternal separation(NMS)model,male SpragueDawley rats were submitted to daily maternal separation from postnatal day 2 to day 14,or no specific handling(NH).Starting from postnatal day 60,rats were administered JCM-16021(2,4,8 g/kg per day)orally twice a day for 28 *** threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System(AD Instruments International),were tested as pain *** in serotonin(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)concentrations in the colon of rats were analyzed;the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry ***:NMS treatment significantly reduced pain threshold pressure(37.4±1.4 mmHg),as compared to that of NH rats(57.7±1.9 mmHg,P<0.05).After JCM-16021 treatment,the pain threshold pressure significantly increased when compared to that before treatment(34.2±0.9 mmHg vs 52.8±2.3 mmHg in the high dose group,40.2±1.6 mmHg vs 46.5±1.3 mmHg in the middle dose group,and 39.3±0.7 mmHg vs 46.5±1.6 mmHg in the low dose group,P<0.05).Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension(CRD),(the meanΔAUC values were:0.17±0.03,0.53±0.15,1.06±0.18,1.22±0.24 in the high dose group;0.23±0.04,0.68±0.17,1.27 ±0.26,1.8±0.3 in the middle dose group;and 0.29 ±0.06,0.8±0.16,1.53±0.24,2.1±0.21 in the low dose group for the pressures 20,40,60,80 mmHg),as compared to the NMS vehicle *** meanΔAUC values were:0.57±0.12,1.33±0.18,2.57±0.37,3.08±0.37 for the pressures 20,40,60,80 mmHg(P

关键词： Analgesia effect Neonatal maternal separation Visceral hyperalgesia Herbal medicine Serotonin pathway

Nonlinear vibrations of electroelastic shells with relatively large shear deformations

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Science China(Physics,Mechanics & Astronomy) 2006年第6期49卷 660-670页

作者： joseph A. Turner Department of Engineering Mechanics University of Nebraska Lincoln NE 68588-0526 U.S.A.

A set of two-dimensional nonlinear equations for thin electroelastic shells in vibrations with moderately large thickness-shear deformations are obtained from the variational formulation of the three-dimensional equations of nonlinear electroelasticity by expanding the mechanical displacement vector and the electric potential into power series in the shell thickness coordinate and retaining lower order terms. As an example,the equations are used to study nonlinear thickness-shear vibrations of a circular cylindrical shell driven by an electric voltage. Nonlinear amplitude-frequency behavior of electric current near strong resonance is obtained.

关键词： piezoelectricity,shell.

The Agricultural-Industrial Partnership for Eliminating Micronutrient Malnutrition: The Investment Bargain of the Decade

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Biomedical and Environmental Sciences 2001年第1期14卷 104-123页

作者： joseph MICHAEL HUNT Senior Health and Nutrition Economist Asian Development Bank Manila Philippines

The limitations of conventional approaches to eliminating micronutrient deficiencies drives the search for a sustainable paradigm. This manuscript argues that the public and private sectors must embark on modernization of the Asian food industry and reorientation of the international agricultural research complex so that nutritionally enriched essential foods will be affordable and accessible to the poor. It is recommended that this partnership take special care of the needs of Asian children. The costs of chronic undernutrition, availability of cost effective strategies, and benefits of sustained nutrition improvement to individuals, families and nations are reviewed. The roles of food fortification, plant breeding and biotechnology, both actual and imminent, are described. The paper concludes that a recast Green Revolution directed to dietary quality may be the key to enhancing the learning and earning capacity of young Asians of the new millenium. “No other technology offers as large an opportunity to improve lives\{…\}at such a low cost and in such a short time\{…\}” World Bank [1] .

关键词： Agriculture Child Welfare Industry Micronutrients Nutrition Policy Biotechnology Child Food Industry Food Fortified Humans Interprofessional Relations Nutrition Disorders Policy Making