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High-affinity mutant Interleukin-13 targeted CAr T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma

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Bioactive Materials 2020年第3期5卷 624-635页

作者： Gloria B.Kim Virginia Aragon-Sanabria Lauren randolph Hali Jiang Joshua A.reynolds Becky S.Webb Achuthamangalam Madhankumar Xiaojun Lian james r.connor Jian Yang Cheng Dong Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA16802United States Department of Neurosurgery M.S.Hershey Medical CenterThe Pennsylvania State UniversityHersheyPA17033United States

Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its *** antigen receptor(CAr)T cell immunotherapy has emerged as a powerful strategy to treat ***-13-receptor-α2(IL13rα2),present in over 75%of GBMs,has been recognized as an attractive candidate for antiglioblastoma ***,we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent,therapeutic nanoparticles and CAr T cells modified with a targeted-quadruplemutant of IL13(TQM-13)shown to have high binding affinity to IL13rα2-expressing glioblastoma cells with low off-target ***-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile,selective,and high-yielding clicking of the *** clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery.T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T *** vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles *** work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.

关键词： Glioblastoma T cells Nanoparticles Targeted drug delivery Citrate polymers Fluorescence

Early gestation chorionic villi-derived stromal cells for fetal tissue engineering

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World Journal of Stem Cells 2015年第1期7卷 195-207页

作者： Lee Lankford Taryn Selby james Becker Volodymyr ryzhuk connor Long Diana Farmer Aijun Wang Department of Surgery University of California Davis Health System Sacramento CA 95817 United States

AIM: To investigate the potential for early gestation placenta-derived mesenchymal stromal cells(PMSCs) for fetal tissue ***: PMSCs were isolated from early gestation chorionic villus tissue by explant culture. Chorionic villus sampling(CVS)-size tissue samples(mean = 35.93 mg)were used to test the feasibility of obtaining large cell numbers from CVS within a clinically relevant timeframe. We characterized PMSCs isolated from 6 donor placentas by flow cytometry immunophenotyping, multipotency assays, and through immunofluorescent staining. Protein secretion from PMSCs was examined using two cytokine array assays capable of probing for over 70 factors in total. Delivery vehicle compatibility of PMSCs was determined using three common scaffold systems: fibrin glue, collagen hydrogel, and biodegradable nanofibrous scaffolds made from a combination of polylactic acid(PLA) and poly(lactic-co-glycolic acid)(PLGA). Viral transduction of PMSCs was performed using a Luciferase-GFPcontaining lentiviral vector and efficiency of transduction was tested by fluorescent microscopy and flow cytometry ***: We determined that an average of 2.09 × 106(SD ± 8.59 × 105) PMSCs could be obtained from CVS-size tissue samples within 30 d(mean = 27 d, SD ± 2.28), indicating that therapeutic numbers of cells can be rapidly expanded from very limited masses of tissue. Immunophenotyping by flow cytometry demonstrated that PMSCs were positive for MSC markers CD105, CD90, CD73, CD44, and CD29, and were negative for hematopoietic and endothelial markers CD45, CD34, and CD31. PMSCs displayed trilineage differentiation capability, and were found to express developmental transcription factors Sox10 and Sox17 as well as neuralrelated structural proteins NFM, Nestin, and S100 β. Cytokine arrays revealed a robust and extensive profile of PMSC-secreted cytokines and growth factors, and detected 34 factors with spot density values exceeding 103. Detected factors had widely div

关键词： Placenta Mesenchymal stromal cells Chorionicvillus Fetal surgery Tissue engineering

The use of feed-grade amino acids in lactating sow diets

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Journal of Animal Science and Biotechnology 2018年第2期9卷 399-406页

作者： Laura Greiner Pairat Srichana james L.Usry Casey Neill Gary L.Allee Joseph connor Kevin J.Touchette Christopher D.Knight Carthage Innovative Sow Solutions LLCCarthageIL 62321USA Department of Animal Science University of Missouri-ColumbiaColumbiaMO 65211USA Charoen Pokphand Group Co. Ltd.14th Floor313 Silom Rd.BangrakBangkok 10500Thailand Ajinomoto Heartland Inc.ChicagoIL 60631USA Micronutrients 1550 Research WayIndianapolisIN 46231USA PIC HendersonvilleTN 37075USA Pipestone USA Novus International Inc.St.CharlesMO 63304USA

Background: The use of feed grade amino acids can reduce the cost of lactation feed. With changing genetics,increasing feed costs, and higher number of pigs weaned with heavier wean weights further evaluation of higher inclusion levels of feed-grade amino acid in lactation diets than previously published is warranted. Two experiments(Exp.) were conducted to determine the optimal inclusion level of L-lysine HCl to be included in swine lactation diets while digestible lysine levels remain constant across dietary treatments and allowing feed grade amino acids to be added to the diet to maintain dietary ratios relative to lysine to maximize litter growth rate and sow reproductive performance. Furthermore, the studies were to evaluate minimal amino acid ratios relative to lysine that allows for optimal litter growth rate and sow reproductive ***: Exp. 1: Increasing L-lysine HCl resulted in similar gilt feed intake, litter, and reproductive *** litter gain from birth to weaning was 2.51, 2.49, 2.59, 2.43, and 2.65 kg/d when gilts were fed 0.00, 0.075,0.150, 0.225, and 0.30% L-lysine HCl, respectively. Exp. 2: The average litter gain from birth to weaning was 2.68,2.73, 2.67, 2.70, and 2.64 kg/d(P re fed 0.1, 0.2, 0.3, 0.4, and 0.4% L-lysine HCl plus valine,respectively. No other differences among dietary treatments were ***: Collectively, these studies demonstrate corn-soybean meal based lactation diets formulated with a constant SID lysine content for all parities containing up to 0.40% L-lysine HCl with only supplemental feed grade threonine and a methionine source have no detrimental effect on litter growth rate and subsequent total born.

关键词： Amino acid ratio Lactation L-lysine Sow

Impact of Social Determinants of Health on the Choice and Use of Long Acting reversible Contraceptives

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Advances in reproductive Sciences 2020年第3期8卷 166-174页

作者： Dani Zoorob connor McNamee Margaret reilly Lindsey Loss james VanHook College of Medicine and Life Sciences The University of Toledo Toledo Ohio USA

Modern women have increased options for birth control with the development of Long Acting reversible Contraceptives (LArCs). These methods are reliable, easy to use, and require less daily maintenance while providing contraception for an extended period of time. However, despite the surge of LArCs as contraceptive options, the prevalence of unintended pregnancies is still alarmingly high in the United States. As LArCs are the most effective reversible method of birth control at preventing pregnancy, and therefore the potential social, financial, and medical complications associated, we examined whether social determinants of health play a role in LArC usage. While parity and marriage do not seem to affect LArC utilization, increased research is needed to determine the effects of race. Age can affect the type of LArC implemented, as younger women prefer implants to intrauterine devices (IUDs). Insurance coverage was an apparent influencer of LArC usage, as low out-of-pocket costs translate to increased utilization. This is linked to socioeconomic status (SES), as lower SES is associated with decreased access to healthcare in general. Increased research is needed in order to draw conclusions about the effects of education, intimate partner violence, geographic location, and other SDH on LArC usage.

关键词： Social Determinants of Health Long Acting reversible Contraceptives Intrauterine Devices Disparities race Family Planning

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人工智能在化学逆合成中的应用

Engineering 2023年第6期25卷 32-50,M0003页

作者： Yinjie Jiang Yemin Yu Ming Kong Yu Mei Luotian Yuan Zhengxing Huang Kun Kuang Zhihua Wang Huaxiu Yao james Zou connor W.Coley Ying Wei College of Computer Science and Technology Zhejiang UniversityHangzhou 310027China Department of Computer Science City University of Hong KongHong Kong 999077China Shanghai Institute for Advanced Study Zhejiang UniversityShanghai 201203China Shanghai Artificial Intelligence Laboratory Shanghai 201203China Department of Computer Science Stanford UniversityStanfordCA 94305–2004USA Department of Chemical Engineering&Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of TechnologyCambridgeMA 02139USA

近年来,人们对通过人工智能(AI)技术解决化学逆合成预测问题产生了巨大的兴趣。与化学家和基于规则的专家系统进行的逆合成预测不同,AI驱动的逆合成预测自动从现成的实验数据集中学习化学知识,以预测反应和逆合成路径。这提供了解决许... 详细信息

近年来,人们对通过人工智能(AI)技术解决化学逆合成预测问题产生了巨大的兴趣。与化学家和基于规则的专家系统进行的逆合成预测不同,AI驱动的逆合成预测自动从现成的实验数据集中学习化学知识,以预测反应和逆合成路径。这提供了解决许多传统挑战的机会,包括专业知识过于繁杂、路线的长度过大和计算成本高。本文描述了当前AI驱动的逆合成预测的概况。我们首先讨论了化学逆合成的数学定义,并回顾了这个问题中的研究挑战。然后,我们回顾相关的AI技术和最新进度,以实现逆合成预测。此外,我们提供了逆合成系统不同部分的全面分类,并调查了AI方法如何重塑每个子模块。最后,我们讨论了未来有希望的研究领域。

关键词：逆合成计算成本数学定义化学知识 AI技术基于规则的专家系统专业知识子模块

Computed tomography and patient risk:Facts,perceptions and uncertainties

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World Journal of radiology 2016年第12期8卷 902-915页

作者： Stephen P Power Fiachra Moloney Maria Twomey Karl james Owen J O'connor Michael M Maher Department of radiology Cork University Hospital

Since its introduction in the 1970s, computed tomography(CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses.

关键词： Computed tomography radiation dose Iterative reconstruction Neoplasia Carcinogenesis

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Marx on Nature

Frontiers of Philosophy in China 2014年第3期9卷 358-369页

作者： james Swindal Department of Philosophy Duquesne University Pittsburgh PA 15282 USA

Ecological Marxists argue that Marx forged a view of nature compatible with more recent models of environmentalism. John Bellamy Foster argues that Marx ascribed an ecological value to nature by asserting a co-evolution between man and nature. james O＇connor presents a more nuanced view in which Marx at best defended a conservationist defense of nature. I argue that such ecological views of Marx tend to overlook his abandonment of an ontology of nature as a totality of relations among physical objects with respect to their interactions and mutual preservation and order. He followed Kant in reducing nature, or the physical world, effectively to a regulative notion, thus reducing its value to a simply a heuristic one for judgments about and actions towards objects. But he also radicalized this reduction by envisaging nature only as a material field of fungible and consumable things, such that each thing is a mere locus of energy or force that human labor cannot substantively perfect but only change to a function. Labor in this view creates new arrangements of natural things for a singular ultimate purpose： the formation of associations of free labor. I conclude that Marx＇s thinking thus cannot be utilized to support an environmental philosophy, such as deep ecology or eco-socialism, that would posit any intrinsic value to nature.

关键词： Kant Marx Engels nature ecology

Outcomes after arthroscopic repair of rotator cuff tears in the setting of mild to moderate glenohumeral osteoarthritis

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World Journal of Orthopedics 2022年第7期13卷 631-643页

作者： Ian S Hong Allison J rao Tyler L CarlLee Joshua D Meade Daniel J Hurwit Gregory Scarola David P Trofa Shadley C Schiffern Nady Hamid Patrick M connor james E Fleischli Bryan Michael Saltzman Department of Orthopedic Surgery Atrium Health Musculoskeletal InstituteCharlotteNC 28207United States Department of Sports Medicine Orthocarolina Research InstituteCharlotteNC 28207United States Department of Orthopedic Surgery Columbia University Irving Medical CenterNew York CityNY 10032United States Department of Orthopaedic Surgery Carolinas Medical CenterCharlotteNC 28207United States Department of Orthopedic Surgery OrthoCarolina Sports Medicine CenterCharlotteNC 28207United States

BACKGrOUND rotator cuff pathology is a very common source of shoulder ***,osteoarthritis of the glenohumeral joint can cause shoulder pain and produce similar *** management can be indicated for both pathologies,however,outcomes data is limited when examining rotator cuff repair(rCr) in the setting of glenohumeral arthritis(GHOA).Thus,this study sought to determine outcomes for patients who undergo rCr in the setting of *** To evaluate if a relationship exists between outcomes of rCr in the setting of *** This was a retrospective analysis of patients who underwent arthroscopic rotator cuff repair with concurrent glenohumeral osteoarthritis between *** were stratified based on rotator cuff tear size and glenohumeral osteoarthritis *** were paired 1:1 with patients without glenohumeral *** included had a minimum two year *** of conversion to total shoulder arthroplasty,complication rates following initial surgery,and patient-reported outcome measures were *** A total of 142 patients were *** number of patients that required total shoulder arthroplasty within two years after index surgery was low.2/71(2.8%) patients with GHOA,and 1/71(1.4%) without *** rotator cuff repair,both groups showed favorable patientreported *** Patients with glenohumeral osteoarthritis who underwent arthroscopic rotator cuff repair showed comparable outcomes to patients without glenohumeral osteoarthritis.

关键词： rotator cuff repair rotator cuff tear Glenohumeral osteoarthritis Shoulder Arthroscopic Outcomes

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

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Advances in Nanoparticles 2012年第3期1卷 44-53页

作者： Nicholas J. Wiley A. B. Madhankumar ryan M. Mitchell Elizabeth B. Neely Elias rizk Gregory L. Douds Zachary Simmons james r. connor Department of Neurology Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA George M. Leader Family Laboratory Department of Neurosurgery Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA

Activation of microglia is a histological feature observed in neurodegenerative diseases like ALS. The oral administration of minocycline has been demonstrated to have minimal neuroprotection ability in the animal models and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows promise in a number of disease models suggesting it could be effective if delivered optimally. Thus, we utilized LPS modified liposomes to target TLr4 receptor on the microglia in SOD1G93A mice and compared its efficacy with non- targeted nanoliposomes. The in vitro results indicate that targeting the TLr4 receptor on microglia significantly increases (p G93A mouse model of ALS, targeted and non-targeted minocycline treatment significantly increased (p G93A mice, the non- targeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

关键词： Amyotrophic Lateral Sclerosis Minocycline Liposomes Microglia TLr4 Lipopolysaccharides