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An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety,tolerability,and immune biomarkers from limited case numbers

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Translational Neurodegeneration 2023年第1期12卷 529-545页

作者： Katherine E.Olson Mai M.Abdelmoaty Krista L.Namminga Yaman Lu Helen Obaro Pamela Santamaria r.lee mosley Howard E.Gendelman Department of Pharmacology and Experimental Neuroscience Center for Neurodegenerative DisordersUniversity of Nebraska Medical CenterOmahaNE 68198USA Great Plains Center for Clinical and Translational research Nebraska MedicineOmahaNEUSA Neurology Consultants of Nebraska PC and Nebraska MedicineOmahaNEUSA

Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s *** safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been *** As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 *** goals included numbers of CD4+T cells and monocytes and motor ***,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/*** 2 years,drug use was discon-tinued for 3 *** was then followed by an additional 6 months of *** Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone *** drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term *** Parkinson’s Disease rating Scale scores remained stable throughout the study while regulatory T cell number and function were *** the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin *** finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile *** Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim *** in larger patient populations is planned in a future phase II evaluation.

关键词： Parkinson’s disease Granulocyte-macrophage colony-stimulating factor Unified Parkinson’s Disease rating Scale regulatory T cells Neuroprotection Sargramostim therapy

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Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders

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Translational Neurodegeneration 2014年第1期3卷 180-203,179页

作者： Kristi M Anderson Katherine E Olson Katherine A Estes Ken Flanagan Howard E Gendelman r.lee mosley Department of Pharmacology and Experimental Neuroscience Center for Neurodegenerative DisordersThe University of Nebraska Medical CenterOmahaNE 68198USA Prothena Biosciences Inc.650 Gateway BoulevardSouth San FranciscoCA 94080USA

Inappropriate T cell responses in the central nervous system(CNS)affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include,but are not limited to,multiple sclerosis,amyotrophic lateral sclerosis,Alzheimer’s disease and Parkinson’s *** the one hand immune responses can exacerbate neurotoxic responses;while on the other hand,they can lead to neuroprotective *** temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent ***,immune responses that affect neurodegeneration may occur within or outside the *** of antigen-specific CD4+T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal *** destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T ***,immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the *** responses with predominate T cell subtypes may differentially manifest migratory,regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific *** final result is altered glial and neuronal behaviors that influence the disease ***,discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.

关键词： Neurodegeneration Neuroprotection Migration MPTP MCAM regulatory T cell Effector T cell,Neuroinflammation

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Evidence of the 1991 Pinatubo volcanic eruption in South Polar snow

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Chinese Science Bulletin 1999年第8期44卷 756-760页

作者： Jihong Cole-Dai Ellen mosley-Thompson Byrd Polar research Center The Ohio State University Columbus OH 43210 USAByrd Polar Research Center The Ohio State University Columbus OH 43210 USA

Traces of tephra and increased sulfate (SO42-) concentrations were identified in the1992-1994 snow layers in 2 firn cores from South Pole. The deposition of the Pinatubo SO42-aerosol was delayed due to the long transport to the high south latitudes and its initial existence at high altitudes in the Antarctic atmosphere. Electron microscopic analyses show that the element composition of the tephra is identical to that of volcanic ash found near the Pinatubo volcano in Philippines. Detailed stratigraphic snow sampling resolved the Pinatubo signal from that of Cerro Hudson eruption during August 1991 in Chile. The South Pole sulfate flux from Pinatubo is calculated to be (10.9 ±1.1) kg·km-2, while the Hudson sulfate flux is (3.2 ± 1.1) kg·km-2. This information will be useful to estimating the magnitudes of the past volcanic eruptions recorded in Antarctic ice core.

关键词： Pinatubo volcanoes Antarctica ice cores.

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Towards a systematic understanding of blockchain governance in proposal voting: A dash case study

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Blockchain(research and Applications) 2022年第3期3卷 89-99页

作者： Lawrence mosley Hieu Pham Xiaoshi Guo Yogesh Bansal Eric Hare Nadia Antony Omni Analytics Group AmesIA50014USA College of Business The University of Alabama in HuntsvilleHuntsvilleAL35899USA Department of Industrial and Manufacturing Systems Engineering Iowa State UniversityAmesIA50014USA Omni Analytics Innovative Technologies Initiative AmesIA50014USA

The transparent and immutable nature of blockchain provides incentives for organizations wishing to create and implement an open,decentralized governance *** members exercise their voting rights,a fault-tolerant record accumulates on the blockchain that can be analyzed to diagnose and intercept potential threats to the governing *** date,there has not been a systematic study of on-chain governance with respect to *** this paper,we provide an analysis of blockchain governance through a case study of the first cryptocurrency to adopt on-chain voting,*** analysis introduces the key characteristics of blockchain governance,steps through a data-driven exploration of Dash's on-chain voting system,and highlights exploitable attack vectors and vulnerabilities for the subversion of Dash's on-chain voting system via a novel network analysis *** then conclude with guidelines for other organizations looking to implement similar blockchain governance solutions while maintaining integrity in their operations.

关键词： Decentralized governance Blockchain Voting systems Data mining Network analysis

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Are “Straight to Test” Pathways Always Best for Patients? A Prospective Observational Study of Two-Week-Wait Colorectal referrals

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Surgical Science 2013年第10期4卷 443-447页

作者： Frances mosley Jon r. Ausobsky John P. Griffith Bradford royal Infirmary Bradford UK Yorkshire and the Humber Deanery Bradford UK

Aim: Many centres have adopted a straight to test approach to deliver a fast-track service for suspected lower GI cancer. We undertook a prospective comparison between patients having a straight to test (STT) flexible sigmoidoscopy and those attending an outpatient appointment (OPA). The study aimed to determine whether STT reduced diagnostic time without additional investigations. Methods: An observational study of 200 consecutive fast-track colorectal referrals was undertaken. Data collected included: patient demographics, whether STT or OPA, investigations undertaken (including dates) and final diagnosis. Outcomes were compared by adjusted linear regression and logistic regression, for numerical and binary outcomes respectively. Potential confounding factors included were: age, gender and whether NICE referral criteria were achieved. results: 186 out of 200 referrals attended their appointment, 62% (116/186) went STT and 38% (70/186) had an OPA. No significant difference was seen in the number of days to final investigation, adjusted coefficient -3.71, 95% C.I. -8.92 to 1.50. The STT group had 0.4 more tests per patient, adjusted 95% C.I. 0.07 to 0.73, than the OPA group. Significantly more patients in the STT group had a flexible sigmoidoscopy in addition to whole colonic imaging (all modalities), compared to the OPA group, adjusted Or of 93.47 (95% C.I. 29.26 to 298.54). Conclusion: This study highlights the potential disadvantages of STT flexible sigmoidoscopy for patients referred under the two-week-rule with suspected lower GI cancer. Despite the previously published work highlighting the potential cost and time benefits, it may come at the sacrifice of exposing patients to additional investigations.

关键词： Colorectal Neoplasms (MeSH) Endoscopy Gastrointestinal (MeSH) Colorectal Surgery (MeSH) 2-Week-Wait Fast-Track Straight to Test (No MeSH Term)

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New evidence for enhanced cosmogenic isotope production rate in the atmosphere ≈37 kaBP from the Guliya ice core

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Chinese Science Bulletin 1999年第17期44卷 1616-1620页

作者： L.G.Thompson E.mosley-Thompson J.Cole-Dai M.E.Davis P.-N.Lin Hyrd Polar research Center Ohio State University OH 45701 USAHyrd Polar Research Center Ohio State University OH 45701 USAHyrd Polar Research Center Ohio State University OH 45701 USAHyrd Polar Research Center Ohio State University OH 45701 USAHyrd Polar Research Center Ohio State University OH 45701 USA

A 36CI peak was found in the predicted section of Guliya ice core, from the Qinghai-Tibetan Plateau, at about 37 kaBP. This cannot be interpreted by means of changes in the accumulation rate, but by the enhanced cosmogenic isotope production rate in the atmosphere. Compared with the records of 10Be and 36CI in the other regions, the peaks of the cosmogenic isotopes are global and can be considered as time marks. An intriguing fact is that the peaks coincided with cold periods.

关键词： Guliya ice core cosmogenic isotope 36Cl global event climatic change.

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A retrospective Chart Assessment of Clinical Outcomes after Amniotic Suspension Allograft Is Used during Spinal Arthrodesis Procedures

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Surgical Science 2016年第3期7卷 150-156页

作者： Joseph A. Sclafani Kevin Liang Darcy mosley Mark Prevost Milestone research Organization San Diego CA USA Southern Orthopedics and Sports Medicine Associates Jasper AL USA

Study Design: This retrospective, non-randomized study was designed to evaluate one-year clinical outcomes in a cohort of patients treated with an amniotic suspension allograft as an adjunct to lumbar interbody fusion. Methods: A single-center chart review was conducted to collect pre-operative and peri-operative data for patients at or beyond the one year post-operative time point. results: Patients underwent either anterior (n = 22) or posterior (n = 65) lumbar interbody fusion. There were six reoperations reported: pseudarthrosis repair (n = 1), adjacent level decompression (n = 2), removal of symptomatic instrumentation (n = 3). Overall VAS score improved from 7.8 ± 1.7 to 5.5 ± 2.4 at 1 year post-op (n = 86, p = 0.0001) and overall ODI score improved from 55 ± 16 to 42 ± 19 at 1 year post-op (n = 85, p = 0.0001). Patients that were 59 years old or older at the time of surgery reported greater improvement in VAS score (3.6 ± 2.3 point improvement, n = 31) than patients younger than 59 at the time of surgery (1.7 ± 2.2 point improvement, n = 55, p = 0.0005). There was not a significant difference in outcome measures between groups when the data were stratified based on patient BMI, tobacco use, previous surgery, or a primary indication of pseudarthrosis repair. Conclusions: These results indicate that there is a significant clinical improvement when amniotic suspension allograft is used during interbody fusion. Patient groups with increased risk of non-union (increased age, previous pseudarthrosis, and tobacco users) demonstrated improvement in one year post-op outcome measures. Improved clinical outcome implies a high rate of successful arthrodesis in both high and low risk patient populations.

关键词： Lumbar Fusion Spine Surgery Stem Cells Clinical Outcome

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伯明翰度假

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海外英语 2013年第10期 38-39页

作者： Jayne mosley

伯明翰曾被评为英国最丑的城市，它也因此被排除在诸多英国旅游景点之外。究竟是什么原因，使伯明翰得此臭名呢？伯明翰难道就没有值得一去的地方吗？下面这篇文章将为我们揭开伯明翰的面纱。

关键词：伯明翰度假旅游景点英国城市

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Modifying light–matter interactions with perovskite nanocrystals inside antiresonant photonic crystal fiber

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Photonics research 2021年第8期9卷 1462-1469页

作者： ANDrEY A.MACHNEV ANATOLY P.PUSHKArEV PAVEL TONKAEV rOMAN E.NOSKOV KrISTINA r.rUSIMOVA PETEr J.mosley SErGEY V.MAKArOV PAVEL B.GINZBUrG IVAN I.SHISHKIN School of Electrical Engineering Tel Aviv UniversityTel Aviv 69978Israel Department of Physics and Engineering ITMO UniversitySaint Petersburg 197101Russia Centre for Photonics and Photonic Materials Department of PhysicsUniversity of BathBath BA27AYUK Photonics and 2D Materials Moscow Institute of Physics and TechnologyDolgoprudny 141700Russia

Structured environments are employed in a plethora of applications to tailor dynamics of light–matter interaction processes by modifying the structure of electromagnetic *** promising example of such a system is antiresonant photonic crystal fibers(Ar-PCFs),which allow light–analyte interactions in a very long *** we probe contribution of microstructuring and nontrivial mode hierarchy on light–matter interactions in Ar-PCFs by investigating lifetime shortening of perovskite(CsPbBr3)nanocrystals grown to fiber *** crystals have been deposited using a wet chemistry approach and then excited by a supercontinuum source in the 450–500 nm *** spectra have been measured and analyzed via the time-correlated single photon counting(TCSPC)technique,unravelling contributions of core and cladding *** lifetime imaging inside an Ar-PCF enables mapping input of various electromagnetic channels into light–matter interaction *** results pave the way for tailoring the dynamics of high-order quantum processes,promoting the concept of Ar-PCF as a light-driven reactor.

关键词： fiber light resonant

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神迹之星

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新东方英语（中英文版） 2005年第6期 110-113页

作者： John mosley 李姝

据《圣经》记载,耶稣出生的时候,天空出现了一颗"神迹之星",昭示这个以色列未来的"王"的诞生,这只是一个传说吗?如果不是,那它又会是什么呢?

关键词：神迹《圣经》耶稣天空天文现象占星家狮子座公元前行星耶稣诞生地

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