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In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

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The Journal of Biomedical Research 2015年第3期29卷 214-223页

作者： Samuel W.Mwololo Joshua M.Mutiso john c.macharia Alain J.Bourdichon Michael M.Gicheru Department of Zoological Sciences Kenyatta University Department of Tropical and Infectious Diseases Institute of Primate Research BPM Bulk Medicine and Pharmaceuticals Production TROPMED GMbH

The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated that the diminazene-chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene-chloroquine combination was safer （Ld50=0.03±0.04） than Amphotericin B （Ld50=0.02±0.01）. Body weight in infected mice increased significantly （P=0.0007） from day 7 to day 37 following infection （P=0.026）. However, body weight remained comparable in all mice groups during treatment （P=0.16）. The diminazene-chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies （P=0.0001） although Amphotericin B was still more efficacious than any other treatment （P=0.0001）. Amongst the test compounds, the diminazene-chloroquine combination showed the lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial antibody responses and protection against disease. These findings demonstrate the positive advantage and the potential use of a combined therapy of diminazene-chloroquine over the constituent drugs. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

关键词： efficacy diminazene-chloroquine combination therapy Leishmania donovani visceral leishmaniasis BALB/c mice

Evaluation of the Therapeutic Potential of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii against Leishmania donovani in vitro and in Balb/c Mice

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Journal of Zoological Research 2022年第4期4卷 1-6页

作者： Maria Divinah Mogaka Joshua M.Mutiso john c.macharia Rebecca M.Ayako Bernard Osero Michael M.Gicheru Department of Zoological Sciences of the School of Pure and Applied Sciences Kenyatta UniversityKenya Department of Tropical and Infectious Diseases Institute of Primate ResearchKenya centre for Biotechnology Research and Development Kenya Medical Research InstituteKenya

Leishmaniasis is a zoonotic disease caused by protozoan parasites of the genus *** chemotherapy remains to be the most preferred measure against leishmaniasis despite being associated with high toxicity and relapse *** are also expensive and require hospitaliza***-based compounds provide a better treatment alternative because they are effective,cheap,and less associated with toxicity and *** study examined the therapeutic potential of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii against Leishmania donovani infection in BALB/c ***-promastigote and toxicity studies were evaluated by incubating the test compound with promastigotes and Vero cells,*** was obtained from the mice for total immunoglobulin gamma(IgG)*** in vivo studies,the mice were infected with virulent Leishmania donovani then treated with methanolic extracts of Warburgia ugandensis,Prunus africana,and Piliostigma thonningii and control drug,pentostam(sodium stibogluconate).Treatment with the plant extracts and standard drug resulted to significant reduction in parasite *** in the mice treated with plant extracts were comparable to those treated with pentostam(P≥0.05).In the promastigote assay,all the test compounds killed more than half of the promastigotes at the highest concentration(500μg/mL).Warburgia ugandensis,***,and *** reduced the number of promastigotes from 2.0×10^(6) to 7.7×10^(3),72.0×10^(3),and 5.0×10^(3),*** had the lowest Ic50(210μg/mL),followed by Warburgia ugandensis(Ic50 of 270μg/mL).Piliostigma thonningii and *** were less toxic with Ic50 of 720μg/mL and 500μg/mL,*** was low production of IgG antibodies following treatment with the plant extracts and high levels in the untreated control.

关键词： Promastigotes Amastigotes Toxicity Parasite burden IgG antibodies

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase cγ-ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

cold plasma redistribution throughout geospace

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Science china(Technological Sciences) 2016年第9期59卷 1340-1345页

作者： Foster john c. Massachusetts Institute of Technology Haystack Observatory

The redistribution of the electrically charged cold plasma of ionospheric origin involves the equatorial,low,mid,auroral,and polar-latitude regions in a multi-step,system-wide process linking the regions of *** with ground and space-based instruments characterize the geospace plume-regularly occurring channels of enhanced plasma density flowing at both ionospheric and magnetospheric *** in the SAPS channel transports the eroded material to the noontime cusp in the ionosphere and to the dayside magnetopause at high *** the fluxes of cold plume plasma traverse the cusp and enter the polar cap,they form the polar tongue of *** the cusp the plume plasma provides a rich source of heavy ions for the magnetospheric injection and acceleration via the mechanisms operative on those field lines.

关键词： plasmasphere ionosphere geospace GPS TEc ionospheric electric field plume

Metagenomics: Facts and Artifacts, and computational challenges

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Journal of computer Science & Technology 2010年第1期25卷 71-81页

作者： john c. Wooley 叶玉珍 center for Research on BioSystems Calit2 University of California San Diego School of Informatics and computing Indiana University

Metagenomics is the study of microbial communities sampled directly from their natural environment, without prior culturing. By enabling an analysis of populations including many （so-far） unculturable and often unknown microbes, metagenomics is revolutionizing the field of microbiology, and has excited researchers in many disciplines that could benefit from the study of environmental microbes, including those in ecology, environmental sciences, and biomedicine. Specific computational and statistical tools have been developed for metagenomic data analysis and comparison. New studies, however, have revealed various kinds of artifacts present in metagenomics data caused by limitations in the experimental protocols and/or inadequate data analysis procedures, which often lead to incorrect conclusions about a microbial community. Here, we review some of the artifacts, such as overestimation of species diversity and incorrect estimation of gene family frequencies, and discuss emerging computational approaches to address them. We also review potential challenges that metagenomics may encounter with the extensive application of next-generation sequencing （NGS） techniques.

关键词： metagenomics next-generation sequencing (NGS) taxonomic/functional profiling statistical approaches comparative metagenomics

Materials-oriented integrated design and construction of structures in civil engineering—A review

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Frontiers of Structural and civil Engineering 2022年第1期16卷 24-44页

作者： Xing MING john c.HUANG Zongjin LI Institute of Applied Physics and Materials Engineering University of MacaoMacao SAR 999078China cHc Engineering LLCFairfaxVA 20030USA

Design is a goal-oriented planning activity for creating products,processes,and systems with desired functions through *** is a decision-making exploration:the design outcome may vary greatly depending on the designer’s knowledge and *** design is one type of design philosophy that takes an interdisciplinary and holistic *** civil engineering,structural design is such an activity for creating buildings and ***,structural design in many countries has emphasized a performance-based philosophy that simultaneously considers a structure’s safety,durability,serviceability,and ***,integrated design in civil engineering has become more popular,useful,and ***-oriented integrated design and construction of structures(MIDcS)combine materials engineering and structural engineering in the design stage:it fully utilizes the strengths of materials by selecting the most suitable structural forms and construction *** paper will explore real-world examples of MIDcS,including the realization of MIDcS in timber seismic-resistant structures,masonry arch structures,long-span steel bridges,prefabricated/on-site extruded light-weight steel structures,fiber-reinforced cementitious composites structures,and fiber-reinforced polymer bridge ***,advanced material design methods such as bioinspired design and structure construction technology of additive manufacturing are briefly reviewed and discussed to demonstrate how MIDcS can combine materials and structures.A unified strengthdurability design theory is also introduced,which is a human-centric,interdisciplinary,and holistic approach to the description and development of any civil infrastructure and includes all processes directly involved in the life cycle of the ***,this paper lays out future research directions for further development in the field.

关键词： integrated design and construction fiber-reinforced concrete fiber-reinforced polymer light-weight steel structures digital fabrication composites

An Improved Evolvable Oscillator and Basis Function Set for control of an Insect-Scale Flapping-Wing Micro Air Vehicle

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Journal of computer Science & Technology 2012年第5期27卷 966-978页

作者： john c.Gallagher Michael W.Oppenheimer Department of computer Science and Engineering Wright State University control Sciences Branch Air Force Research Laboratory

This paper introduces an improved evolvable and adaptive hardware oscillator design capable of supporting adaptation intended to restore control precision in damaged or imperfectly manufactured insect-scale flapping-wing micro air vehicles. It will also present preliminary experimental results demonstrating that previously used basis function sets may have been too large and that significantly improved learning times may be achieved by judiciously culling the oscillator search space. The paper will conclude with a discussion of the application of this adaptive, evolvable oscillator to full vehicle control as well as the consideration of longer term goals and requirements.

关键词： evolvable and adaptive hardware micro air vehicle evolutionary algorithm

An electrochemical process that uses an Fe^0/TiO2 cathode to degrade typical dyes and antibiotics and a bio-anode that produces electricity

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Frontiers of Environmental Science & Engineering 2016年第4期10卷 25-32页

作者： chaojie Jiang Lifen Liu john c. crittenden Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education) School of Environmental Science and Technology Dalian University of Technology Dalian 116024 China School of civil and Environmental Engineering Georgia Institute of Technology Atlanta GA 30332 USA

In this study a new water treatment system that couples （photo-） electrochemical catalysis （PEc or Ec） in a microbial fuel cell （MFc） was configured using a stainless-steel （SS） cathode coated w th Fe / TiO2. We examined the destruction of methylene blue （MB） and tetracycline. Fe^0/TiO2 was prepared using a chemical reduction-deposition method and coated onto an SS wire mesh （500 mesh） using a sol technique. The anode generates electricity using microbes （bio-anode）. connected via wire and ohmic resistance, the system requires a short reaction time and operates at a low cost by effectively remowng 94% MB （initial concentration 20 mg·L^-1） and 83% TOc/TOco under visible light illumination （50 W; 1.99 mW·cm^-2 for 120 rain, MFc-PEc）. The removal was similar even without light irradiation （MFc-Ec）. The EEo of the MFc-PEc system was approximately 0.675 kWh·m^-3. order-l whereas that of the MFc-Ec system was zero. The system was able to remove 70% cOD in tetracycline solution （initial tetracycline concentration 100 mg·L^-1） after 120 min of visible light illumination; without light, the removal was 15% lower. The destruction of MB and tetracycline in both traditional photocatalysis and photoelectrocatalysis systems was notably low. The electron spinresonance spectroscopy （ESR） study demonstrated that. OH was formed under visible light, and. 02 was formed without light. The bio-electricity-activated O2 and ROS （reactive oxidizing species） generation by Fe^0/TiO2 effectively degraded the pollutants. This cathodic degradation improved the electricity generation by accepting and consuming more electrons from the bio-anode.

关键词： Bio-anodePhotocatalytic cathode Fe^0/TiO2 ESRDye and antibioticsAdvanced oxidation

Gastroesophageal reflux disease and severe obesity:Fundoplication or bariatric surgery?

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World Journal of Gastroenterology 2010年第30期16卷 3757-3761页

作者： Vivek N Prachand john c Alverdy center for the Surgical Treatment of Obesity Department of SurgeryUniversity of Chicago Pritzker School of MedicineChicagoIL 60637United States

Increases in the prevalence of obesity and gastroesophageal reflux disease (GERD) have paralleled one another over the past decade, which suggests the possibility of a linkage between these two processes. In both instances, surgical therapy is recognized as the most effective treatment for severe, refractory disease. current surgical therapies for severe obesity include (in descending frequency) Roux-en-Y gastric bypass, adjustable gastric banding, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch, while fundoplication remains the mainstay for the treatment of severe GERD. In several large series, however, the outcomes and durability of fundoplication in the setting of severe obesity are not as good as those in patients who are not severely obese. As such, bariatric surgery has been suggested as a potential alternative treatment for these patients. This article reviews current concepts in the putative pathophysiological mechanisms by which obesity contributes to gastroesophageal reflux and their implications with regards to surgical therapy for GERD in the setting of severe obesity.

关键词： Morbid obesity Gastroesophageal reflux disease Fundoplication Bariatric surgery Gastric bypass Sleeve gastrectomy