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Interim results from ongoing PhaseⅢ placebo-controlled,randomized trial of hepcortespenlisimut-L for advanced hepatocellular carcinoma indication

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Hepatoma Research 2020年第1期6卷 11-18页

作者： Aldar S.Bourinbaiar Jigjidsuren Chinburen Purev Batchuluun Chogsom Munkhzaya DandiiOyungerel Dorjiin Dandii Galyna A.Kutsyna Hulan Tsogkhuu Marina G.Tarakanovskaya alan a.reid Vika Borisova Allen I.Bain Vichai Jirathitikal Immunitor Inc. VancouverBCV6K 2G8Canada National Cancer Center Ulaanbaatar 14000Mongolia National Center for Public Health Ulaanbaatar 13000Mongolia National Cancer Institute National Institutes of HealthBethesdaMD 20892USA Ekomed LLC Ulaanbaatar 13381Mongolia Immunitor China Ltd. ChaoyangBeijing 100027China

Aim:We aimed to further investigate the role of hepcortespenlisimut-L(Hepko-V5 or V5),a new oral immunotherapy developed by us,for hepatocellular carcinoma(HCC)***:The interim data from ongoing PhaseⅢplacebo-controlled,randomized trial were evaluated on the initial group of patients in advanced stage of HCC with emphasis on liver function and tumor marker alpha-fetoprotein ***,an in vitro study was undertaken to elucidate the mechanism of action of V5 by measuring with flow cytometry the expression of cytokines such as IL-2,INF-γ,and TNF-αand cell activation markers CD69 and Ki67 on CD4-and CD8-positive lymphocytes isolated from peripheral blood of healthy ***:As early as one month after treatment initiation,there was a clear improvement in alanine transaminase,aspartate transaminase,alkaline phosphatase,and bilirubin levels among HCC patients who received daily dose of V5,but not in the placebo ***,alpha-fetoprotein(AFP)levels among V5 recipients decreased,while in the ;placebo group they *** results are in line with in vitro observations indicating immune activation,as evidenced by many-fold enhancement of CD69,Ki67,and INF-γexpression and at the same time marked anti-inflammatory effect resulting in 10-fold decrease in TNF-αoutput and lack of influence on IL-2 ***:Hepcortespenlisimut-L,a tableted oral formulation derived from heat-inactivated pooled blood of patients with HCC and viral hepatitis shows beneficial clinical effect,as demonstrated by improvement in liver function and reduction of tumor marker AFP *** correlate with in vitro observations showing potent activation of the immune response and pronounced oral tolerance effect.

关键词： Hepatocellular carcinoma alpha-fetoprotein alanine transaminase aspartate transaminase IL-2 INF-γ TNF-α CD69 Ki67 CD4 CD8 T lymphocytes

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Development of gradient boosting-assisted machine learning data-driven model for free chlorine residual prediction

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Frontiers of Environmental Science & Engineering 2024年第2期18卷 35-46页

作者： Wiley Helm Shifa Zhong Elliot reid Thomas Igou Yongsheng Chen School of Civil and Environmental Engineering Georgia Institute of TechnologyAtlantaGA 30332USA School of Ecological and Environmental Sciences East China Normal UniversityShanghai 200241China

Chlorine-based disinfection is ubiquitous in conventional drinking water treatment (DWT) and serves to mitigate threats of acute microbial disease caused by pathogens that may be present in source water. An important index of disinfection efficiency is the free chlorine residual (FCR), a regulated disinfection parameter in the US that indirectly measures disinfectant power for prevention of microbial recontamination during DWT and distribution. This work demonstrates how machine learning (ML) can be implemented to improve FCR forecasting when supplied with water quality data from a real, full-scale chlorine disinfection system in Georgia, USA. More precisely, a gradient-boosting ML method (CatBoost) was developed from a full year of DWT plant-generated chlorine disinfection data, including water quality parameters (e.g., temperature, turbidity, pH) and operational process data (e.g., flowrates), to predict FCR. Four gradient-boosting models were implemented, with the highest performance achieving a coefficient of determination, R2, of 0.937. Values that provide explanations using Shapley’s additive method were used to interpret the model’s results, uncovering that standard DWT operating parameters, although non-intuitive and theoretically non-causal, vastly improved prediction performance. These results provide a base case for data-driven DWT disinfection supervision and suggest process monitoring methods to provide better information to plant operators for implementation of safe chlorine dosing to maintain optimum FCR.

关键词： Machine learning Data-driven modeling Drinking water treatment Disinfection Chlorination

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Generalized Hopfian Property, a Minimal Haken Manifold, and Epimorphisms Between 3-Manifold Groups

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Acta Mathematica Sinica,English Series 2002年第1期18卷 157-172页

作者： reid alan W Department of Mathematics. University of Texas Austin. TX 78712. USA

We address the question that if π_1-surjective maps between closed aspherical 3-manifolds have the same rank on π_1 they must be of non-zero degree. The positive answer is proved for Seifert manifolds, which is used in constructing the first known example of minimal Haken manifold. Another motivation is to study epimorphisms of 3-manifold groups via maps of non-zero degree between 3- manifolds. Many examples are given.

关键词： Non-zero degree maps Epimorphisms 3-Manifolds

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A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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Carbohydrate biomarkers for future disease detection and treatment

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Science China Chemistry 2010年第1期53卷 3-20页

作者： reid Suazette Department of Chemistry Georgia State University

Carbohydrates are considered as one of the most important classes of biomarkers for cell types,disease states,protein functions,and developmental ***"binders"that can specifically recognize a carbohydrate biomarker can be used for developing novel types of site specific delivery methods and imaging *** this review,we present selected examples of important carbohydrate biomarkers and how they can be targeted for the development of therapeutic and diagnostic *** are arranged based on disease categories including(1) infectious diseases,(2) cancer,(3) inflammation and immune responses,(4) signal transduction,(5) stem cell transformation,(6) embryo development,and(7) cardiovascular diseases,though some issues cross therapeutic boundaries.

关键词： carbohydrates biomarkers imaging agents boronolectins

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Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

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Acta Pharmacologica Sinica 2007年第4期28卷 540-548页

作者： Paul reid Celtic Biotech LtdDublinIreland

Aim:To investigate the role of crotoxin (CrTX)-induced autophagy in the death ofMCF-7 cells,a caspase-3-deficient,human breast cancer cell ***:Cul-tured MCF-7 cells were treated with various doses of CrTX,a phospholipase A2(PLA2) isolated from the venom of the South American rattlesnake,Crotalusdurissus *** cytotoxicity of CrTX in the presence and absence ofcaspase inhibitors was measured with methyl thiazolyl tetrazolium (MTT) andlactate dehydrogenase (LDH) leakage *** activation of autophagy wasdetermined with transmission electron microscope and monodansylcadaverin(MDC) *** upregulation of lysosomal enzymes,the release of cyto-chrome c (cyto-c),and the nuclear translocation of the apoptosis inducing factor(AIF) were examined by immunoblotting and ***:CrTXinhibited the viability of MCF-7 cells in a dose-and time-dependent ***-activated autophagy was revealed by punctuate MDC labeling,and an increase inthe formation of autophagosomes as well as apoptosis,as evidenced by nuclearcondensation and *** activation of cathepsin B,D,and L,inaddition to the release of cytochrome c and the relocation of AIF into nuclei,wereobserved after CrTX *** inhibitors 3-methyladenine (3-MA),NH4Cl,and the pan-caspase inhibitor,Z-Val-Ala-Asp-fluoromethylketone (Z-Vad-fmk),attenuated CrTX-induced cell ***:An autophagic mecha-nism contributes to the apoptosis of MCF-7 cells induced by CrTX.

关键词： crotoxin autophagy apoptosis cytochrome c apoptosis inducing factor

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Tracking the Cretaceous transcontinental Ceduna River through Australia:The hafnium isotope record of detrital zircons from offshore southern Australia

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Geoscience Frontiers 2016年第2期7卷 237-244页

作者： Jarred Lloyd alan S.Collins Justin L.Payne Stijn Glorie Simon Holford Anthony J.reid Centre for Tectonics Resources and Exploration(TRaX)Department of Earth SciencesThe University of Adelaide Centre for Tectonics Resources and Exploration(TRaX)School of Built and Natural EnvironmentsThe University of South Australia Centre for Tectonics Resources and Exploration(TRaX)Australian School of PetroleumThe University of Adelaide Geological Survey of South Australia Department of State DevelopmentGovernment of South Australia

The middle-upper Cretaceous Ceduna River system traversed continental Australia from the NE coast to the centre of the southern coast. At its mouth, it formed a vast delta system that is similar in scale to the Niger delta of West Africa. The delta system is composed of two main lobes that represent different phases of delta construction. A recent hypothesis has challenged the traditional idea that both lobes of the delta were derived from a transcontinental river system by suggesting that the upper lobe （Santonian -Maastrichtian） is instead derived from a restricted catchment within southern Australia. Hf isotopic data presented here fingerprint the original source of the upper delta lobe zircons to NE Australia, with data comparing well with similar U-Pb and Lu-Hf isotopic data from the Lachlan Orogen, the New England Orogen, the eastern Musgraves Province and the northern Flinders Ranges. These data do not preclude a model where the lobe is derived from recycled Eromanga Basin sediments during a phase of late Cretaceous inland Australian uplift, but when coupled with reconnaissance low-temperature thermochronometry from the region of the Ceduna River course indicating widespread Triassic-Jurassic exhumation, and comparisons with detrital zircon data from the Winton Formation upstream of any proposed uplift, we suggest that both lobes of the Ceduna Delta are likely to be derived from a transcontinental Ceduna River.

关键词： Detrital zircon Hf U-Pb Ceduna sub-basin Bight basin Australia

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An apatite U-Pb thermal history map for the northern Gawler Craton,South Australia

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Geoscience Frontiers 2018年第5期9卷 1293-1308页

作者： James W.Hall Stijn Glorie Anthony J.reid Samuel C.Boone alan S.Collins ANDrew Gleadow Tectonics Resources and Exploration (TRaX) Department of Earth Sciences University of Adelaide Geological Survey of South Australia Department of State Development School of Earth Sciences The University of Melbourne

Apatite U-Pb thermochronology was applied to granitoid basement samples across the northern Gawler Craton to unravel the Proterozoic, post-orogenic, cooling history and to examine the role of major fault zones during cooling. Our observations indicate that cooling following the ~2500 Ma Sleaford Orogeny and ~1700 Ma Kimban Orogeny is restricted to the Christie and Wilgena Domains of the central northern Gawler Craton. The northern Gawler Craton mainly records post-Hiltaba Event(~1590 Ma) U-Pb cooling ages. Cooling following the ~1560 Ma Kararan Orogeny is preserved within the Coober Pedy Ridge,Nawa Domain and along major shear zones within the south-western Fowler Domain. The Nawa Domain samples preserve U-Pb cooling ages that are >150 Ma younger than the samples within the Coober Pedy Ridge and Fowler Domain, indicating that later(~1300 Ma) fault movement within the Nawa Domain facilitated cooling of these samples, caused by arc collision in the Madura Province of eastern Western Australia. When compared to^(40)Ar/^(39) Ar from muscovite, biotite and hornblende, our new apatite U-Pb ages correlate well, particularly in regions of higher data density. Our data also preserve a progressive younging of U-Pb ages from the nucleus of the craton to the periphery with a stark contrast in U-Pb ages across major structures such as the Karari Shear Zone and the Southern Overthrust, which indicates the timing of reactivation of these major crustal structures. Although this interpolation was based solely on thermochronological data and did not take into account structural or other geological data, these maps are consistent with the structural architecture of the Gawler Craton and reveal the thermal footprint of known tectonic and magmatic events in the Gawler Craton.

关键词： Apatite U-Pb Gawler Craton Karari Shear Zone Thermochronology Hiltaba event

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