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Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson’s disease

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Neural Regeneration Research 2021年第6期16卷 1099-1104页

作者： steven Vetel Laura Foucault-Fruchard Claire Tronel Frédéric Buron Jackie Vergote Sylvie Bodard Sylvain Routier Sophie Sérrière Sylvie Chalon UMR 1253 iBrainUniversitéde ToursInsermToursFrance CHU Tours Service pharmacieToursFrance Institut de Chimie Organique et Analytique ICOAUMR CNRS 7311Universitéd’OrléansOrléansFrance

To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson’s *** was recently observed in a rodent model of Alzheimer’s disease that the interaction between the α7 subtype of nicotinic acetylcholine receptor(α7-nAChR)and sigma-1 receptor(σ1-R)could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson’s *** this context,the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide(PHA)543613 as an α7-nAChR agonist and 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate(PRE)-084 as aσ1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson’s *** animals received either vehicle separately or the dual therapy PHA/PRE once a day until day 14 *** no effect was noticed in the amphetamine-induced rotation test,our data has shown that the PHA/PRE treatment induced partial protection of the dopaminergic neurons(15-20%),assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia ***,this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion,i.e,the 18 kda translocation protein density and glial fibrillary acidic protein staining in the striatum,and the Cd11b and glial fibrillary acidic protein staining in the substantia ***,this study reports for the first time that concomitant activation of α7-nAChR andσ1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial *** study was approved by the Regional Ethics Committee(CEEA Val de Loire n°19)validated this protocol(Authorization N°00434.02)on May 15,2014.

关键词： 6-hydroxydopamine astrocytes microglial activation neurodegeneration neuroinflammation nicotinicα7 receptor Parkinson’s disease PHA 543613 PRE-084 sigma-1 receptor

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Relational and Euclidean Temporal Space

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Journal of Applied Mathematics and Physics 2024年第2期12卷 683-719页

作者： steven d. P. Moore Independent Researcher Milton Canada

In mathematics, space encompasses various structured sets such as Euclidean, metric, or vector space. This article introduces temporal space—a novel concept independent of traditional spatial dimensions and frames of reference, accommodating multiple object-oriented durations in a dynamical system. The novelty of building temporal space using finite geometry is rooted in recent advancements in the theory of relationalism which utilizes Euclidean geometry, set theory, dimensional analysis, and a causal signal system. Multiple independent and co-existing cyclic durations are measurable as a network of finite one-dimensional timelines. The work aligns with Leibniz’s comments on relational measures of duration with the addition of using discrete cyclic relational events that define these finite temporal spaces, applicable to quantum and classical physics. Ancient formulas have symmetry along with divisional and subdivisional orders of operations that create discrete and ordered temporal geometric elements. Elements have cyclically conserved symmetry but unique cyclic dimensional quantities applicable for anchoring temporal equivalence relations in linear time. We present both fixed equivalences and expanded periods of temporal space offering a non-Greek calendar methodology consistent with ancient global timekeeping descriptions. Novel applications of Euclid’s division algorithm and Cantor’s pairing function introduce a novel paired function equation. The mathematical description of finite temporal space within relationalism theory offers an alternative discrete geometric methodology for examining ancient timekeeping with new hypotheses for Egyptian calendars.

关键词： Relationalism Pairing Function Equation discrete Euclidean Timelines Ancient Timekeeping

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Soil microbial activity and community structure as affected by exposure to chloride and chloride-sulfate salts

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Journal of Arid Land 2018年第5期10卷 737-749页

作者： ZHANG Qianqian steven A WAKELIN LIANG Yongchao CHU Guixin College of Life Science Shaoxing University department of Resources and Environmental Science College of Agriculture/the Key Laboratory of Oasis Eco-agriculture of the Xinjiang Production and Construction Corps Shihezi University College of Resources and Environmental Sciences Nanjing Agricultural University department of Forest Systems Scion Research Ministry of Education Key Laboratory of Environment Remediation and Ecological Health College of Environmental & Resource Sciences Zhejiang University

Mixed or chloride salty ions dominate in saline soils, and exert wide-ranging adversely affect on soil biological processes and soil functions. The objectives of this study were to（1） explore the impacts of mixed（0, 3, 6, 10, 20 and 40 g Cl–/SO42–salt/kg dry soil） and chloride（0, 1.5, 3, 5, 8 and 15 g Cl– salt/kg dry soil） salts on soil enzyme activities, soil physiological functional（Biolog） profiles and microbial community structure by using soil enzymatic, Biolog-Eco microplates as well as denaturing gradient gel electrophoresis（dEEG） methods, and（2） determine the threshold concentration of soil electronic conductivity（EC1：5） on maintaining the functional and structural diversity of soil microbial community. The addition of either Cl– or mixed Cl–/SO42–salt obviously increased soil EC, but adversely affected soil biological activities including soil invertase activity, soil microbial biomass carbon（MBC） and substrate-induced respiration（SIR）. Cl– salt showed a greater deleterious influence than mixed Cl–/SO42–salt on soil enzymes and MBC, e.g., the higher soil MBC consistently appeared with Cl–/SO42–instead of Cl– treated soil. Meanwhile, we found that SIR was more reliable than soil basal respiration（SBR） on explaining the changes of soil biological activity responsive to salt disturbance. In addition, microbial community structures of the soil bacteria, fungi, and Bacillus were obviously affected by both salt types and soil EC levels, and its diversity increased with increasing of mixed Cl–/SO42–salt rates, and then sharply declined down after it reached critical point. Moreover, the diversity of fungal community was more sensitive to the mixed salt addition than other groups. The response of soil physiological profiles（Biolog） followed a dose-response pattern with Cl–（R2=0.83） or mixed Cl–/SO42–（R2=0.89） salt. The critical threshold concentrations of salts for soil physiological function were 0.45 d S/m for Cl– and 1.26 d S/m for Cl–/SO42–, and those for soil

关键词： soil biological activity microbial diversit3T chloride salt mixed salt threshold concentration

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Advancements in Time Modeling: Relationalism, divisional Structures, and Geometry

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Journal of Applied Mathematics and Physics 2024年第10期12卷 3358-3383页

作者： steven d. P. Moore Independent Researcher Milton Canada

This article broadens terminology and approaches that continue to advance time modelling within a relationalist framework. Time is modeled as a single dimension, flowing continuously through independent privileged points. Introduced as absolute point-time, abstract continuous time is a backdrop for concrete relational-based time that is finite and discrete, bound to the limits of a real-world system. We discuss how discrete signals at a point are used to temporally anchor zero-temporal points [t = 0] in linear time. Object-oriented temporal line elements, flanked by temporal point elements, have a proportional geometric identity quantifiable by a standard unit system and can be mapped on a natural number line. durations, line elements, are divisible into ordered unit ratio elements using ancient timekeeping formulas. The divisional structure provides temporal classes for rotational (Rt24t) and orbital (Rt18) sample periods, as well as a more general temporal class (Rt12) applicable to either sample or frame periods. We introduce notation for additive cyclic counts of sample periods, including divisional units, for calendar-like formatting. For system modeling, unit structures with dihedral symmetry, group order, and numerical order are shown to be applicable to Euclidean modelling. We introduce new functions for bijective and non-bijective mapping, modular arithmetic for cyclic-based time counts, and a novel formula relating to a subgroup of Pythagorean triples, preserving dihedral n-polygon symmetries. This article presents a new approach to model time in a relationalistic framework.

关键词： Relationalism Mohist Geometry Euclidean Geometry Relational-Time discrete-Time Continuous-Time Planck Time Zero-Time

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Separating Space and Time for dimensional Analysis and Euclidean Relational Modeling

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Journal of Applied Mathematics and Physics 2023年第9期11卷 2704-2738页

作者： steven d. P. Moore Independent Researcher Milton Canada

The theory of relativity links space and time to account for observed events in four-dimensional space. In this article we describe an alternative static state causal discrete time modeling system using an omniscient viewpoint of dynamical systems that can express object relations in the moment(s) they are observed. To do this, three key components are required, including the introduction of independent object-relative dimensional metrics, a zero-dimensional frame of reference, and application of Euclidean geometry for modeling. Procedures separate planes of matter, extensions of space (relational distance) and time (duration) using object-oriented dimensional quantities. Quantities are converted into base units using symmetry for space (dihedral360), time (dihedral12), rotation (dihedral24), and scale (dihedral10). Geometric elements construct static state outputs in discrete time models rather than continuous time using calculus, thereby using dimensional and positional natural number numerals that can visually encode complex data instead of using abstraction and irrationals. Static state Euclidean geometric models of object relations are both measured and expressed in the state they are observed in zero-time as defined by a signal. The frame can include multiple observer frames of reference where each origin, point, is the location of a distinct privileged point of reference. Two broad and diverse applications are presented: a one-dimensional spatiotemporal orbital model, and a thought experiment related to a physical theory beyond Planck limits. We suggest that expanding methodologies and continued formalization, novel tools for physics can be considered along with applications for computational discrete geometric modeling.

关键词： Spacetime Relationalism Quantum Classical Signal discrete Geometry

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Using a temporal phylogenetic method to harmonize familyand genus-level classification in the largest clade of lichen-forming fungi

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Fungal diversity 2017年第3期84卷 101-117页

作者： Pradeep K.divakar Ana Crespo Ekaphan Kraichak steven d.Leavitt Garima Singh Imke Schmitt H.Thorsten Lumbsch departamento de Biología Vegetal II Facultad de FarmaciaUniversidad Complutense de Madrid28040 MadridSpain department of Botany Faculty of ScienceKasetsart UniversityBangkokThailand department of Biology and M.L.Bean Life Science Museum Brigham Young University4102 Life Science BuildingProvoUT 84602USA department of Biological Sciences Institute of EcologyEvolution and DiversityGoethe Universitat and Senckenberg Biodiversity and Climate Research Centre(BiK-F)Frankfurt am MainGermany Science&Education The Field MuseumChicagoILUSA

Although classification at supra-specific ranks is inherently arbitrary,comparable taxonomic ranks within clades can facilitate more consistent classifications and objective comparisons among *** circumscriptions of the hyper-diverse lichen-forming fungal family Parmeliaceae and widely different generic circumscriptions among authors have been *** this study,we use a recently developed temporal approach that uses timecalibrated chronograms to identify temporal bands for specific ranks in Parmeliaceae and allied groups with the overarching goal of establishing a consistent,stable classification.A data set of 330 species,representing 73 genera in the family and 52 species of related families was used to address the circumscription of Parmeliaceae and its genera following the proposed temporal *** on the results of this study,we propose a revised,temporal-based classification for Parmeliaceae,including all clades that share a common ancestor 102.13–112.88 Ma for families and a time window of 29.45–32.55 Ma for *** of the currently accepted genera in Parmeliaceae were supported in their current *** subfamilies are accepted within Parmeliaceae:Protoparmelioideae divakar et ***.,including Protoparmelia and the resurrected genus Maronina,and Parmelioideae,including the bulk of genera in the *** new genus Austromelanelixia divakar et *** proposed to accommodate a clade of southern Hemisphere species previously included in *** and tentatively dolichousnea are resurrected as genera separate from *** following genera are reduced to synonymy:Allocetraria,Cetrariella,Usnocetraria,and Vulpicida with Cetraria;Arctocetraria,Cetreliopsis,Flavocetraria,Kaernefeltia,Masonhalea,Tuckermanella,and Tuckermannopsis with Nephromopsis;and the lichenicolous genera Nesolechia and Raesaenenia with the lichen-forming genera Punctelia and Protousnea,respectively.A total of 47 new combinations and

关键词： Ascomycota Gypsoplacaceae Lecanorales Lichenized fungi Parmeliaceae Phylogeny Protoparmelia Taxonomy Taxonomicranks

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Extra-pancreatic complications,especially hemodialysis predict mortality and length of stay,in ICU patients admitted with acute pancreatitis

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Gastroenterology Report 2018年第3期6卷 202-209,I0001页

作者： darshan Kothari Maarten R.Struyvenberg Michael C.Perillo Ghideon Ezaz steven d.Freedman Sunil G.Sheth department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical School330 Brookline AveBostonMA 02215USA

Background and aims:Patients in the intensive care unit(ICU)with acute pancreatitis(AP)are at risk for extra-pancreatic complications given their severe illness and prolonged length of *** sought to determine the rate of extra-pancreatic complications and its effect on length of stay(LOS)and mortality in ICU patients with ***:We performed a retrospective cohort study of ICU patients admitted to a tertiary-care center with a diagnosis of AP.A total of 287 ICU patients had a discharge diagnosis of AP,of which 163 met inclusion *** calculated incidence rates of extra-pancreatic complications and performed a univariate and multi-variable analysis to determine predictors of LOS and ***:There were a total of 158 extra-pancreatic complications(0.97 extra-pancreatic complications per patient).Ninetyfive patients had at least one extra-pancreatic complication,whereas 68 patients had no extra-pancreatic *** with extra-pancreatic complications had a significantly longer LOS(14.7 vs 8.8 days,pd a higher rate of mortality(24.0%vs 16.2%,p=0.04).Patients requiring dialysis was an independent predictor for LOS and mortality(incidence risk ratio[IRR]1.73,95%confidence interval[CI]:1.263–2.378 and IRR 1.50,95%CI 1.623–6.843,pdictor for mortality(p=0.05).Other extra-pancreatic complications were not ***:Extra-pancreatic complications occur frequently in ICU patients with AP and impact *** with noninfectious extra-pancreatic complications have a higher mortality *** controlling for local pancreatic complications,patients requiring dialysis remained an independent predictor for LOS and mortality.

关键词： Severe acute pancreatitis extra-pancreatic complications intensive care unit length of stay in-hospital mortality infections

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The role of MT1-MMP in the progression and metastasis of osteosarcoma

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 564-578页

作者： Hannah L.M.Spencer steven d.Shnyder Paul M.Loadman Robert A.Falconer Institute of Cancer Therapeutics Faculty of Life SciencesUniversity of BradfordBradford BD71DPUK

The dysregulation of Membrane-type 1 matrix metalloproteinase(MT1-MMP)has been extensively studied in numerous cancer types,and plays key roles in angiogenesis,cancer progression,and ***1-MMP is a predictor of poor prognosis in osteosarcoma(OS),yet the molecular mechanisms of disease progression are *** review provides a summary of the literature relating to the gene and protein expression of MT1-MMP(MMP-14)in OS clinical samples,evaluates the expression in cell lines and experimental models,and analyses its potential role in the progression and metastasis of *** addition,the therapeutic potential of MT1-MMP as a drug target has been *** to the biological complexity of MMPs,inhibition has proven to be ***,exploiting the expression and proteolytic capacity of MT1-MMP could open new avenues in the search for novel,safer and selective drugs for use in OS.

关键词： Matrix metalloproteinase membrane-type osteosarcoma MT1-MMP

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A boronic acid-based fluorescent hydrogel for monosaccharide detection

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Frontiers of Chemical Science and Engineering 2020年第1期14卷 112-116页

作者： Suying Xu Adam C.Sedgwick Souad A.Elfeky Wenbo Chen Ashley S.Jones George T.Williams A.Toby A.Jenkins steven d.Bull John S.Fossey Tony d.James department of Biochemistry Faculty of ScienceBeijing University of Chemical TechnologyBeijing 100029China department of Chemistry University of BathBath BA27AYUK department of Chemistry University of Texas at AustinTX 78712-1224USA School of Chemistry University of BirminghamBirmingham B152TTUK National Institute of Laser Enhanced Sciences Cairo UniversityGiza 12613Egypt Higher Institute for Optics Technology SheratonCairo 17361Egypt Shanghai Key Laboratory of Materials Protection and Advanced Materials in Electric Power Shanghai University of Electric PowerShanghai 200090China

A boronic acid-based anthracene fluorescent probe was functionalised with an acrylamide unit to incorporate into a hydrogel system for monosaccharide *** solution,the fluorescent probe displayed a strong fluorescence turn-on response upon exposure to fructose,and an expected trend in apparent binding constants,as judged by a fluorescence response where d-fructose>d-galactose>d-mannose>*** hydrogel incorporating the boronic acid monomer demonstrated the ability to detect monosaccharides by fluorescence with the same overall trend as the monomer in solution with the addition of d-fructose resulting in a 10-fold enhancement(≤0.25 mol/L).

关键词： boron hydrogel monomer

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Machine learning-based prediction of trace element concentrations using data from the Karoo large igneous province and its application in prospectivity mapping

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Artificial Intelligence in Geosciences 2021年第1期2卷 60-75页

作者： steven E.Zhang Glen T.Nwaila Julie E.Bourdeau Lewis d.Ashwal SmartMin Limited 39 Kiewiet StreetHelikon Park1759South Africa School of Geosciences University of the Witwatersrand1 Jan Smuts AveJohannesburg2000South Africa Geological Survey of Canada 601 Booth StreetOttawaOntarioK1A 0E8Canada

In this study,we present a machine learning-based method to predict trace element concentrations from major and minor element concentration data using a legacy lithogeochemical database of magmatic rocks from the Karoo large igneous province(Gondwana Supercontinent).Wedemonstrate that a variety of trace elements,including most of the lanthanides,chalcophile,lithophile,and siderophile elements,can be predicted with excellent *** finding reveals that there are reliable,high-dimensional elemental associations that can be used to predict trace elements in a range of plutonic and volcanic *** the major and minor elements are used as predictors,prediction performance can be used as a direct proxy for geochemical *** such,our proposed method is suitable for prospective exploration by identifying anomalous trace element *** to multivariate compositional data analysis methods,the new method does not rely on assumptions of stoichiometric combinations of elements in the data to discover geochemical *** we do not use multivariate compositional data analysis techniques(*** component analysis and combined use of major,minor and trace elements data),we also show that log-ratio transforms do not increase the performance of the proposed approach and are unnecessary for algorithms that are not spatially aware in the feature ***,we demonstrate that high-dimensional elemental associations can be modelled in an automated manner through a data-driven approach and without assumptions of stoichiometry within the *** approach proposed in this study can be used as a replacement method to the multivariate compositional data analysis technique that is used for prospectivity mapping,or be used as a pre-processor to reduce the detection of false geochemical anomalies,particularly where the data is of variable quality.

关键词： Machine learning Predictive modelling Compositional data Prospectivity mapping Anomaly detection Karoo igneous province

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