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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez daniel Refai Gerald R.Rodts Christian mustroph David Gimbel Jonathan Grossberg daniel L.Barrow matthew F.Gary Ali m.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： mackenzie m.Spicer Jianqi Yang daniel Fu Alison N.DeVore marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in molecular medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

The spatial variability of actual evapotranspiration across the Amazon River Basin based on remote sensing products validated with flux towers

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Ecological Processes 2019年第1期8卷 67-86页

作者： Victor Hugo da motta Paca Gonzalo E.Espinoza-Dávalos Tim m.Hessels daniel medeiros moreira Georges F.Comair Wim G.m.Bastiaanssen IHE Delft Institute for Water Education Westvest 7Delft 2611 AXNetherlands TU Delft DelftNetherlands CPRm-Geological Survey of Brazil Rio de JaneiroBrazil World Bank WashingtonD.C.USA

Actual evapotranspiration(ET)is a major component of the water *** several international flux measurement programs have been executed in the tropical rain forest of the Amazon,those measurements represent the evaporative process at a few selected sites *** aim of this study is to obtain the spatial distribution of ET,using remote sensing techniques,across the entire Amazon River *** from six global ET products based on remote sensing techniques(GLEAm,SEBS,ALEXI,CmRSET,mOD16,and SSEBop)were merged to obtain an ensemble prediction of the ET rates for the complex and in-accessible environment of the Amazon at a spatial resolution of 250 *** study shows that the basinwide average ET is 1316 mm/year with a standard deviation of 192 mm/*** new ET-Amazon product was validated against seven different historic flux tower *** energy balance closure of the in situ measurements varied between 86 and 116%.Only months with more than 70%completeness of in situ measurements were considered for *** procedures for closure correction were included in the *** correlation between measured and remotely sensed ET is good(R2>0.97 for consecutive periods of 2 to 12months),and the bias correction is negligible for the energy balance residual method,which seemed most *** ET values have more *** monthly RmSE values vary between 7.4 and 27.8 mm/month(the average RmSE is 22.2mm/month),and the coefficient of determination(R2)varies between 0.48 and 0.87(the average R2 is 0.53).The ET from the water balance is 1380 mm/year,being−64 mm/year difference and 4.6%less than ET derived from the water *** evaporation from the Amazon basin inside Brazil is 5063 km3/year,followed by Peru with 1165 km3/***-Amazon shows more spatial details and accuracy than alternative global ET products such as LandFlux-EVAL,model Tree Ensemble(mTE),and *** justifies the development of new regional ET pro

关键词： Amazon River Basin Evapotranspiration Flux towers measurements ET-Amazon product

Exploiting Caenorhabditis elegans to discover human gut microbiota-mediated intervention strategies in protein conformational diseases

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Neural Regeneration Research 2022年第10期17卷 2203-2204页

作者： daniel m.Czyż Department of microbiology and Cell Science University of FloridaGainesvilleFLUSA

Age-dependent protein-conformational diseases(PCDs),such as Alzheimer’s disease(AD),Parkinson’s disease(PD),or amyotrophic lateral sclerosis(ALS),are characterized by misfolding and aggregation of metastable proteins present within the proteome of the affected *** evidence supports the notion that bacteria and bacterial products may be affecting the stability of these culprit host proteins and therefore influence disease progression and perhaps even its *** specific culprit proteins are associated with each disease(e.g.,Aβin AD,α-synuclein in PD,and TDP-43 in ALS),bacteria found to affect these diseases do not seem to differentiate between these specific proteins but likely affect host proteostasis in general,leading to misfolding of metastable proteins encoded within the *** evidence that supports this hypothesis comes from studies where a single bacterial genus was linked to multiple *** example,a decrease in Prevotella *** linked to constipation,a condition that precedes PD motor symptoms by as much as 20 or more years(Savica et al.,2009;Zhu et al.,2014).

关键词： diseases Alzheimer folding

A CALCULUS FOR SERVICES INNOVATION

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Journal of Systems Science and Systems Engineering 2007年第2期16卷 129-165页

作者： James m. TIEN daniel BERG Department of Decision Sciences and Engineering Systems Rensselaer Polytechnic Institute Troy New York USA

Innovation in the services area - especially in the electronic services （e-services） domain - can be systematically developed by first considering the strategic drivers and foci, then the tactical principles and enablers, and finally the operational decision attributes, all of which constitute a process or calculus of services innovation. more specifically, there are four customer drivers （i.e., collaboration, customization, integration and adaptation）, three business foci （i.e., creation-focused, solution-focused and competition-focused）, six business principles （i.e., reconstruct market boundaries, focus on the big picture not numbers, reach beyond existing demand, get strategic sequence right, overcome organizational hurdles and build execution into strategy）, eight technical enablers （i.e., software algorithms, automation, telecommunication, collaboration, standardization, customization, organization, and globalization）, and six attributes of decision informatics （i.e., decision-driven, information-based, real-time, continuously-adaptive, customer-centric and computationally-intensive）. It should be noted that the four customer drivers are all directed at empowering the individual - that is, at recognizing that the individual can, respectively, contribute in a collaborative situation, receive customized or personalized attention, access an integrated system or process, and obtain adaptive real-time or just-in-time input. The developed process or calculus serves to identify the potential white spaces or blue oceans for innovation. In addition to expanding on current innovations in services and related experiences, white spaces are identified for possible future innovations; they include those that can mitigate the unforeseen consequences or abuses of earlier innovations, safeguard our rights to privacy, protect us from the always-on, interconnected world, provide us with an authoritative search engine, and generate a GDP metric that can adequately measure the gro

关键词： Services innovation decision informatics software algorithms automation globalization collaboration customization integration adaptation standardization telecommunication organization business principles

Near-field terahertz nonlinear optics with blue light

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Light(Science & Applications) 2023年第5期12卷 838-846页

作者： Angela Pizzuto Pingchuan ma daniel m.mittleman Department of Physics Brown UniversityProvidence RI 02912USA School of Engineering Brown UniversityProvidence RI 02912USA

The coupling of terahertz optical techniques to scattering-type scanning near-field microscopy(s-SNOm)has recently emerged as a valuable new paradigm for probing the properties of semiconductors and other materials on the *** have demonstrated a family of related techniques,including terahertz nanoscopy(elastic scattering,based on linear optics),time-resolved methods,and nanoscale terahertz emission ***,as with nearly all examples of s-SNOm since the technique’s inception in the mid-1990s,the wavelength of the optical source coupled to the near-field tip is long,usually at energies of 2.5 eV or *** in coupling of shorter wavelengths(i.e.,blue light)to the nanotip has greatly inhibited the study of nanoscale phenomena in wide bandgap materials such as Si and ***,we describe the first experimental demonstration of s-SNOm using blue *** femtosecond pulses at 410 nm,we generate terahertz pulses directly from bulk silicon,spatially resolved with nanoscale resolution,and show that these signals provide spectroscopic information that cannot be obtained using near-infrared *** develop a new theoretical framework to account for this nonlinear interaction,which enables accurate extraction of material *** work establishes a new realm of possibilities for the study of technologically relevant wide-bandgap materials using s-SNOm methods.

关键词： scattering optics nonlinear

Sizing of hybrid PmSG-PV system for battery charging of electric vehicles

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Frontiers in Energy 2015年第1期9卷 68-74页

作者： m. m. RAJAN SINGARAVEL S. ARUL daniel Department of Electrical and Electronics Engineering National Instituteof Technology Tiruchirappalli 620015 India

The number of electric vehicles are increasing in the society as they are considered as zero emission vehicles and also because conventional fuels are becoming expensive. Additional electrical power should be produced to meet the energy requirement of this increase in electric vehicle population. To use the existing grid infrastructure without any failure, installing distributed generator at secondary distribution network is essential. In this work, sizing of wind-driven permanent magnet synchronous generator photovoltaic hybrid distributed generating system has been attempted to meet the energy demand of electric vehicles of a particular residential area. Different feasible combinations for wind generator capacity and photovoltaic capacity are obtained to satisfy the additional energy requirement. Results are analyzed based on energy, financial payback periods and daily power profile of the hybrid system. Based on this analysis, the sizes of wind generator and photovoltaic array have been chosen to meet the energy demand of electric vehicles of that particular residential locality.

关键词： electric vehicles hybrid PmSG-PV system,smart grid

ON SERVICES RESEARCH AND EDUCATION

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Journal of Systems Science and Systems Engineering 2006年第3期15卷 257-283页

作者： James m.TIEN daniel BERG Department of Decision Sciences and Engineering Systems Rensselaer Polytechnic Institute

The importance of the services sector can not be overstated; it employs 82.1 percent of the U. S. workforce and 69 percent of graduates from an example technological university. Yet, university research and education have not followed suit. Clearly, services research and education deserve our critical attention and support since services - and services innovation - serve as an indispensable engine for global economic growth. The theme of this paper is that we can and should build services research and education on what has occurred in manufacturing research （especially in regard to customization and intellectual property） and education; indeed, services and manufactured goods become indistinguishable as they are jointly co-produced in real-time. Fortunately, inasmuch as manufacturing concepts, methodologies and technologies have been developed and refined over a long period of time （i.e., since the 1800s）, the complementary set of concepts, methodologies and technologies for services are more obvious. However, while new technologies （e.g., the Internet） and globalization trends have served to enable, if not facilitate, services innovation, the same technologies （e.g., the Internet） and 21st Century realities （e.g., terrorism） are making services innovation a far more complex problem and, in fact, may be undermining previous innovations in both services and manufacturing. Finally, there is a need to define a ＂knowledge-adjusted＂ GDP metric that can more adequately measure the growing knowledge economy, one driven by intangible ideas and services innovation.

关键词： Services manufacturing customization innovation education intellectual property

Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system

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Asian Journal of Andrology 2018年第2期20卷 120-130页

作者： T Hugh Jones daniel m Kelly Robert Hague Centre for Diabetes and Endocrinology Barnsley Hospital NHS Foundation Trust Barnsley UK Academic Unit of Diabetes Endocrinology and Metabolism Department of Oncology and Metabolism University of Sheffield Medical School Sheffield UK Biomedical Research Centre Sheffield Hallam University Sheffield UK

Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （L-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the

关键词： cardiovascular testosterone testosterone replacement