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Why do‘OFF’periods still occur during continuous drug delivery in Parkinson’s disease?

Translational Neurodegeneration 2022年第1期11卷 280-293页

作者： Silvia Rota Daniele Urso Daniel J.van Wamelen Valentina Leta Iro Boura Per Odin Alberto J.Espay Peter Jenner k.ray chaudhuri Department of Basic and Clinical Neurosciences Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK Parkinson’s Foundation Centre of Excellence King’s College HospitalLondonUK Department of Neuroimaging Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK Centre for Neurodegenerative Diseases and the Aging Brain Department of Clinical Research in NeurologyUniversity of Bari‘Aldo Moro“Pia Fondazione Cardinale G.Panico”73039 TricaseItaly Donders Institute for Brain Cognition and BehaviourDepartment of NeurologyRadboud University Medical CentreNijmegenThe Netherlands School of Medicine University of CreteCreteGreece Department of Neurology University Hospital of HeraklionCreteGreece Division of Neurology Department of Clinical Sciences LundLund UniversityLundSweden University of Cincinnati Gardner Neuroscience Institute Gardner Family Center for Parkinson’s Disease and Movement DisordersDepartment of NeurologyUniversity of CincinnatiCincinnatiOHUSA Institute of Pharmaceutical Sciences Faculty of Life Science and MedicineKing’s College LondonLondonUK.

Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.

关键词： ‘OFF’periods Continuous drug delivery Continuous dopaminergic stimulation Rotigotine patch Subcutaneous apomorphine infusion Levodopa-carbidopa intestinal gel

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Numerical simulation of square shaped particle sedimentation

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Particuology 2024年第1期84卷 107-116页

作者： Govind Sharma Bahni ray Department of Mechanical Engineering Indian Institute of Technology DelhiHauz KhasNew Delhi110016India

Direct numerical simulations of square particle sedimentation in a viscous incompressible fluid are presented to examine the effects of sharp edges for various particle-to-fluid density ratios and different initial inclination angles.The settling process exhibits four different motion regimes;non-oscillatory,non-uniform centered oscillatory,uniform off-centered oscillatory,and non-uniform off-centered(irregular)oscillatory.At moderate density ratios,we observe that the rotational motion of settling square particle varies with the initial inclination angle.We employ Dynamic Time Warping and Fast Fourier Transform to analyze translational and angular velocities.Oscillating systems are described using phase-space plots,and a chaotic phenomenon is observed at a higher density ratio.

关键词： Sedimentation Distributed Lagrangian multiplier Phase synchronization Oscillations

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TALYS calculation and a short review of the experimental status of proton capture studies on p-nuclei:A guide to future investigation

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Chinese Physics C 2024年第6期48卷 102-111页

作者： Indrani ray Argha Deb Physics Department Jadavpur UniversityKolkata-700032India

TALYS calculations were performed to obtain the theoretical proton capture cross-sections on the p-nuclei.A short review on the status of related experimental studies was also conducted.Some basic properties such as Q-values,Coulomb barrier,Gamow peak,Gamow Window,and decay properties of the parent and daughter nuclei were studied.Various experimental parameters,e.g.,beam energy,beam current,targets,and detectors,used in experimental investigations reported in the literature,were tabulated.The results of the TALYS calculations in the Gamow region were compared with the corresponding experimental values wherever available.This study is expected to facilitate the planning of future experiments.

关键词： p-nuclei proton capture cross-section gamma ray Gamow energy TALYS TENDL kADoNis

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Population Dynamics in an Advective Environment

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Communications on Applied Mathematics and Computation 2024年第1期6卷 399-430页

作者： king-Yeung Lam ray Lee Yuan Lou Department of Mathematics The Ohio State UniversityColumbusOH43210USA School of Mathematical Sciences CMA-Shanghai and MOE-LSCShanghai Jiao Tong UniversityShanghai200240China

We consider a one-dimensional reaction-diffusion equation describing single-and two-species population dynamics in an advective environment,based on the modeling frameworks proposed by Lutscher et al.in 2006.We analyze the effect of rate of loss of individuals at both the upstream and downstream boundaries.In the single-species case,we prove the existence of the critical domain size and provide explicit formulas in terms of model parameters.We further derive qualitative properties of the critical domain size and show that,in some cases,the critical domain size is either strictly decreasing over all diffusion rates,or monotonically increasing after first decreasing to a minimum.We also consider competition between species differing only in their diffusion rates.For two species having large diffusion rates,we give a sufficient condition to determine whether the faster or slower diffuser wins the competition.We also briefly discuss applications of these results to competition in species whose spatial niche is affected by shifting isotherms caused by climate change.

关键词： Reaction-diffusion-advection Critical domain size Competition Climate change

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Neuroprotective role of Noggin in spinal cord injury

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Neural Regeneration Research 2023年第3期18卷 492-496页

作者： Nadia Al-Sammarraie Mohammed Mahmood Swapan k.ray Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSCUSA

Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most instances.Recent research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord development.Noggin is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord injury.In this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord injury.Second,we discuss the current research knowledge about the neuroprotective role of Noggin in preclinical models of spinal cord injury.Lastly,we explain the gap in the knowledge for the use of Noggin in the treatment of spinal cord injury.The results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord injury.Furthermore,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lacking and therefore needs further investigation.

关键词： apoptosis astrocyte differentiation axon myelination axon regeneration bone morphogenetic protein glial scar heterotrophic ossification neurogenesis neuropathic pain Noggin spinal cord injury

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A Power Management Scheme for Grid-connected PV Integrated with Hybrid Energy Storage System

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Journal of Modern Power Systems and Clean Energy 2022年第4期10卷 954-963页

作者： Anindya Bharatee Pravat k.ray Arnab Ghosh Department of Electrical Engineering National Institute of TechnologyRourkela769008India

The penetration of renewable energy sources(RESs)in the distribution system becomes a challenge for the reliable and safe operation of the existing power system.The sporadic characteristics of sustainable energy sources along with the random load variations greatly affect the power quality and stability of the system.Hence,it requires storage systems with both high energy and high power handling capacity to coexist in microgrids.An efficient energy management structure is designed in this paper for a grid-connected PV system combined with hybrid storage of supercapacitor and battery.The combined supercapacitor and battery storage system grips the average and transient power changes,which provides a quick control for the DC-link voltage,i.e.,it stabilizes the system and helps achieve the PV power smoothing.The average power distribution between the power grid and battery is done by checking the state of charge(SOC)of a battery,and an effective and efficient energy management scheme is proposed.Additionally,the use of a supercapacitor lessens the current stress on the battery system during unexpected disparity in the generated power and load requirement.The performance and efficacy of the proposed energy management scheme are justified by simulation studies.

关键词： Hybrid microgrid power management hybrid energy storage arrangement supercapacitor battery

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Type 2 diabetes in children and adolescents:Exploring the disease heterogeneity and research gaps to optimum management

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World Journal of Clinical Pediatrics 2024年第2期13卷 80-99页

作者： Subhodip Pramanik Sunetra Mondal Rajan Palui Sayantan ray Department of Endocrinology Neotia Getwel Multi-specialty hospitalSiliguri 734010West BengalIndia Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of Endocrinology All India Institute of Medical SciencesBhubaneswarBhubaneswar 751019OdishaIndia

Over the past 20 years,the incidence and prevalence of type 2 diabetes mellitus(T2DM)in children and adolescents have increased,particularly in racial and ethnic minorities.Despite the rise in T2DM in children and adolescents,the pathophysiology and progression of disease in this population are not clearly understood.Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM.Furthermore,the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients,mostly due to the challenges of implementing clinical trials.A better understanding of the mechanisms underlying the development and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies.This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

关键词： Type 2 diabetes mellitus Children and adolescents Pathophysiology Heterogeneity Complications Treatment options Barriers

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Continuous flow pyrolysis of virgin and waste polyolefins:a comparative study,process optimization and product characterization

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Frontiers of Chemical Science and Engineering 2024年第6期18卷 133-149页

作者： Ecrin Ekici Güray Yildiz Magdalena Joka Yildiz Monika kalinowska ErolŞeker Jiawei Wang karlsruhe Institute of Technology Institute of Catalysis Research and TechnologyEggenstein-Leopoldshafen 76344Germany Izmir Institute of Technology Faculty of EngineeringDepartment of Energy Systems EngineeringIzmir 35430Türkiye Department of Materials Engineering and Production Faculty of Mechanical EngineeringBialystok University of TechnologyBialystok 15-351Poland Department of Agricultural and Food Engineering and Environmental Development Institute of Civil Engineering and EnergeticsFaculty of Civil Engineering and Environmental SciencesBialystok University of Technology15-351 BialystokPoland Department of Chemistry Biology and BiotechnologyInstitute of Civil Engineering and EnergeticsFaculty of Civil Engineering and Environmental SciencesBialystok University of TechnologyBialystok 15-351Poland Izmir Institute of Technology Faculty of EngineeringDepartment of Chemical EngineeringIzmir 35430Türkiye Energy and Bioproducts Research Institute(EBRI) Aston UniversityBirmingham B47ETUnited Kingdom

Under optimal process conditions,pyrolysis of polyolefins can yield ca.90 wt%of liquid product,i.e.,combination of light oil fraction and heavier wax.In this work,the experimental findings reported in a selected group of publications concerning the non-catalytic pyrolysis of polyolefins were collected,reviewed,and compared with the ones obtained in a continuously operated bench-scale pyrolysis reactor.Optimized process parameters were used for the pyrolysis of waste and virgin counterparts of high-density polyethylene,low-density polyethylene,polypropylene and a defined mixture of those(i.e.,25:25:50 wt%,respectively).To mitigate temperature drops and enhance heat transfer,an increased feed intake is employed to create a hot melt plastic pool.With 1.5 g·min^(-1) feed intake,1.1 L·min^(-1) nitrogen flow rate,and a moderate pyrolysis temperature of 450℃,the formation of light hydrocarbons was favored,while wax formation was limited for polypropylene-rich mixtures.Pyrolysis of virgin plastics yielded more liquid(maximum 73.3 wt%)than that of waste plastics(maximum 66 wt%).Blending polyethylenes with polypropylene favored the production of liquids and increased the formation of gasoline-range hydrocarbons.Gas products were mainly composed of C3 hydrocarbons,and no hydrogen production was detected due to moderate pyrolysis temperature.

关键词： waste plastics polyolefins chemical recycling pyrolysis alternative fuels waste-to-energy

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Geochemistry of volcanic glass from Mahanadi offshore region,eastern continental margin of India:Constraints on the contribution of latest Toba super-eruption

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Acta Oceanologica Sinica 2024年第2期43卷 111-119页

作者： Muralidhar kocherla Durbar ray Manavalan Satyanarayanan Hilda Joao Virsen Gaikwad PB Ramamurty CSIR-National Institute of Oceanography Dona Paula 403004GoaIndia CSIR-National Geophysical Research Institute Uppal RoadHyderabad 500007India

The tephra layers in multiple sediment cores from the offshore region of the Mahanadi basin in the northern Bay of Bengal were investigated for possible volcanic sources. The glass shards from those tephra layers were studied for size distribution, texture, and elemental geochemistry to establish chronostratigraphic markers for regional and global Quaternary correlation. The textural features of fine-grained(silty) volcanic glasses suggest the distal source of these tephra deposits. Major element composition with elevated SiO_(2) contents ranging between75%–76% and dominance of k_(2)O(> 4.5%) over CaO(k trace element compositions of the same glass shards were comparable with those reported in the youngest Toba tephra reported elsewhere. Likewise, the LREE-dominated chondrite normalized REE profiles of tephra from the Mahanadi basin closely resemble the characteristic REE patterns in Toba ash from other parts of the Indian Ocean and thus confirmed the contribution of the youngest Toba super-eruption for this ash layers.

关键词： Mahanadi basin Bay of Bengal volcanic glass glass morphology glass-chemistry

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Long non-coding RNA BANCR promotes pancreatic cancer lymphangiogenesis and lymphatic metastasis by regulating the HIF-1α/VEGF-C/VEGFR-3 pathway via miR-143-5p

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Genes & Diseases 2024年第4期11卷 57-60页

作者： Shaolong Hao Yu Ji Weixuan Pan Hao Sun Fang Nie Jonathan ray Warren Yuchuan Ding Wei Han Department of General Surgery Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Central Laboratory Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Neurosurgery Wayne State University School of MedicineJohn D.Dingell VA Medical CenterDetroitMI 48201USA

Pancreatic cancer is one of the most aggressive malignant tumors of the digestive system.Lymph node metastasis(LNM),as the main way of invasion and metastasis,can occur in the early stage of pancreatic cancer and be considered the most important factor affecting the clinical treatment and prognosis of patients with pancreatic cancer.

关键词： metastasis cancer invasion

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