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Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis

Neural regeneration research 2017年第8期12卷 1262-1267页

作者： rebecca M.Heidker Mitchell r.emerson steven M.Le Vine Department of Molecular and Integrative Physiology University of Kansas Medical Center Department of Pharmaceutical Sciences College of Pharmacy-Glendale Midwestern University

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth： insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

关键词： acetyl-coenzyme A carboxylase biotin estrogen iron Kynurenine pathway mitochondria thyroidhormone remyelination stem cells vitamin D

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Gastric cancer in Alaska Native people: A cancer health disparity

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World Journal of Gastroenterology 2018年第25期24卷 2722-2732页

作者： Holly A Martinson Nancy J Shelby steven r Alberts Matthew J Olnes WWAMI School of Medical education University of Alaska Anchorage Department of Oncology Mayo Clinic Cancer Center Hematology and Medical Oncology Department Alaska Native Medical Center

AIM To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native(AN) people. MeTHODS A retrospective analysis of the Alaska Native Medical Center patient database was performed. Patient history, clinical, pathological, response to treatment and patient outcomes were collected from one-hundred and thirty-two AN gastric cancer patients. The Surveillance, epidemiology and end result database 18 was used to collect comparison United States non-Hispanic White(NHW) and AN gastric cancer patient data between *** AN gastric cancer patients have a higher incidence rate, a poorer overall survival, and are diagnosed at a significantly younger age compared to NHW patients. AN patients differ from NHW patients in greater prevalence of non-cardia, diffuse subtype, and signet ring cell carcinomas. AN females were more likely to be diagnosed with later stage cancer, stage IV, compared to AN males. Diminished overall survival was observed among AN patients with increasing stage, O+ blood type, es examined at resection, and no treatment. This study is the first report detailing the clinicopathologic features of gastric cancer in AN people with outcome *** Our findings confirm the importance of early detection, treatment, and surgical resection for optimizing AN patient outcomes. Further research on early detection markers are warranted.

关键词： Alaska Native gastric cancer Helicobacter pylori gender health disparities

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NADPH oxidase-1 deficiency offers little protection in Salmonella typhimurium-induced typhlitis in mice

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World Journal of Gastroenterology 2016年第46期22卷 10158-10165页

作者： Fong-Fong Chu r steven esworthy James H Doroshow Binghui Shen Department of Gastroenterology and Hepatology The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology Department of Cancer Genetics and epigenetics Beckman Research Institute of City of Hope Center for Cancer research and Division of Cancer Treatment and Diagnosis National Cancer Institute

AIM To test whether Nox1 plays a role in typhlitis induced by Salmonella enterica serovar Typhimurium(S. Tm) in a mouse *** eight-week-old male wild-type(WT) and Nox1 knockout(KO) C57BL6/J(B6) mice were administered metronidazole water for 4 d to make them susceptible to S. Tm infection by the oral route. The mice were given plain water and administered with 4 different doses of S. Tm by oral gavage. The mice were followed for another 4 d. From the time of the metronidazole application, the mice were observed twice daily and weighed daily. The ileum, cecum and colon were removed for sampling at the fourth day post-inoculation. Portions of all three tissues were fixed for histology and placed in rNAlater for m rNA/c DNA preparation and quantitative real-time PCr. The contents of the cecum were recovered for estimation of S. Tm *** We found Nox1-knockout(Nox1-KO) mice were not more sensitive to S. Tm colonization and infection than WT B6 mice. This conclusion is based on the following observations:(1) S. Tm-infection induced similar weight loss in Nox1-KO mice compared to WT mice;(2) the same S. Tm CFU was recovered from the cecal content of Nox1-KO and WT mice regardless of the inoculation dose, except the lowest inoculation dose(2 × 106 CFU) for which the Nox1-KO had one-log lower CFU than WT mice;(3) there is no difference in cecal pathology between WT and Nox1-KO groups; and(4) there are no S. Tm infection-induced changes in gene expression levels(IL-1b, TNF-α, and Duox2) between WT and Nox1-KO groups. The Alpi gene expression was more suppressed by S. Tm treatment in WT than the Nox1-KO cecum. CONCLUSION Nox1 does not protect mice from S. Tm colonization. Nox1-KO provides a very minor protective effect against S. Tm infection. Using NOX1-specific inhibitors for colitis therapy should not increase risks in bacterial infection.

关键词： Knockout mouse NADPH Oxidase-1 Salmonella typhimurium Goblet cells reactive oxygen species

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First demonstration of an all-solid-state optical cryocooler

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Light(Science & Applications) 2018年第1期7卷 922-931页

作者： Markus P.Hehlen Junwei Meng Alexander r.Albrecht eric r.Lee Aram Gragossian steven P.Love Christopher e.Hamilton richard I.epstein Mansoor Sheik-Bahae Los Alamos National Laboratory P.O.Box 1663Los AlamosNM 87545USA Department of Physics&Astronomy University of New MexicoAlbuquerqueNM 87131USA

Solid-state optical refrigeration uses anti-Stokes fluorescence to cool macroscopic objects to cryogenic temperatures without *** such as Yb3+-doped YLiF4(YLF:Yb)have previously been laser-cooled to 91 *** this study,we show for the first time laser cooling of a payload connected to a cooling crystal.A YLF:Yb crystal was placed inside a Herriott cell and pumped with a 1020-nm laser(47 W)to cool a HgCdTe sensor that is part of a working Fourier Transform Infrared(FTIr)spectrometer to 135 *** first demonstration of an all-solid-state optical cryocooler was enabled by careful control of the various desired and undesired heat *** heating of the payload was minimized by using a single-kink YLF thermal link between the YLF:Yb cooling crystal and the copper coldfinger that held the HgCdTe *** adhesive-free bond between YLF and YLF:Yb showed excellent thermal *** laser-cooled assembly was then supported by silica aerogel cylinders inside a vacuum clamshell to minimize undesired conductive and radiative heat loads from the warm *** structure can serve as a baseline for future optical cryocooler devices.

关键词： optical pumped desired

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Coevolution of Male and Female response Preferences to Sexual Signals in Music Frogs

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Asian Herpetological research 2016年第2期7卷 87-95页

作者： Jianguo CUI Jichao WANG Guangzhan FANG Xiaowei SONG steven e.BrAUTH Yezhong TANG Chengdu Institute of Biology Chinese Academy of Sciences Ministry of education Key Laboratory for Tropical Animal and Plant ecology College of Life SciencesHainan Normal University School of Life Sciences Xinyang Normal University Department of Psychology University of MarylandCollege Park

Male signaling influences both female choice and male-male competition. Although male signaling characteristics and female preferences have been shown to coevolve in many species, few studies have examined whether male signal characteristics and male receiver responses related to male-male competition also coevolve. The present study tested the hypothesis that male and female signal receiver preferences may coevolve in parallel for flogs in the genus Babina by comparing the acoustic structure of male advertisement calls of four closely related and geographically isolated Babina species. Then we assessed the behavioral responses of both male and female B. daunchina （emei music frog） to male call playbacks from each of the four species. The results support the hypothesis that male and female signal receiver preferences have coevolved in this species. Specifically, both male and female B. daunchina respond strongly to the heterospecific calls of B. hainanensis, suggesting that preexisting biases exist in both females and males. Both male and female individuals showed a slight response to the calls of B. adenopleura while no response was evoked by the calls ofB. lini. The manifestation of similar response profiles in male and female B. daunchina to the calls of the four species support the idea that male and female signal receiver preferences evolved in parallel and that the origin of these receiver biases reflects adaptations dependent on the same neural and cognitive systems in both sexes.

关键词： sexual selection acoustic communication male-male competition phonotaxis tests coevolution

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emerging applications of tumour-educated platelets in the detection and prognostication of ovarian cancer

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Protein & Cell 2023年第8期14卷 556-559页

作者： Jiewei Zhu Vasily Giannakeas steven A.Narod Mohammad r.Akbari Women's College research Institute Women's College HospitalUniversity of TorontoTorontoOntario M5S 1B2Canada Department of Medicine University of TorontoTorontoOntario MSS 1ACanada Institute of Medical Science Faculty of MedicineUniversity of TorontoTorontoOntario MSS 1ACanada Dalla Lana School of Public Health University of TorontoTorontoOntario MSS 1ACanada

Platelets are nuclear cell fragments produced by *** platelets circulate in the blood until activation by extemal stimuli to execute important biological functions,including hemostasis,inflammation,tissue remodelling,and blood vessel *** can reflect cancer cells'pathogenesis through a process known as tumour-educated platelets(TePs).

关键词： Platelet tumour platelets

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Thermodynamic analysis of metal segregation in dual phase high entropy ceramics

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Journal of Materiomics 2024年第4期10卷 889-895页

作者： steven M.Smith II William G.Fahrenholtz Gregory e.Hilmas Stefano Curtarolo Missouri University of Science and Technology Materials Science and Engineering DepartmentRollaMO65409USA Duke University Department of Mechanical Engineering and Materials ScienceDurhamNC27708USA Duke University Center of Autonomous Materials DesignDurhamNC27708USA

equilibrium Gibbs'free energy calculations were used to determine metal segregation trends between boride and carbide solid solutions containing two metals that are relevant to dual phase high entropy *** model predicted that Ti had the strongest tendency to segregate to the boride phase followed by Zr,Nb,Mo,V,Hf,and Ta,which matches experimental results of measured *** ratio of a metal in the carbide phase to the content of the same metal in the corresponding metal boride had a linear trend with the change in standard Gibbs'free energy of reaction for a metal carbide reacting with B_(4)C to produce its corresponding metal boride and *** proposed model was used to predict the changes in standard Gibbs'free energy for CrC→CrB_(2) to be−260 kJ and WC→WB_(2) to be 148 kJ,which indicates that Cr has the strongest segregation to the boride and W has the strongest segregation to the *** proposed model can be used to estimate the segregation of metals in dual phase high entropy boride-carbide ceramics of any boride/carbide ratio or metal content.

关键词： Dual phase High entropy ceramic Boride Carbide Thermodynamics

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Achieving Better educational Practices Through research evidence:A Critical Analysis and Case Illustration of Benefits and Challenges

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eCNU review of education 2021年第1期4卷 108-127页

作者： steven M.ross Jennifer r.Morrison Johns Hopkins University

Purpose:We examine considerations regarding the positive contributions of evidence accountability and challenges that frustrate educators in gaining access to the needed product ***/Approach/Methods:We review the research literature on the multiple characteristics of evidence relative to consumer(practitioner)*** then examine,through a"case illustration"of an initiative in a large school district,a second challenge for evidence usage-conducting viable studies and interpreting outcomes from comprehensive interventions in complex educational ***:Despite attention being given to rigorous evidence,consumers report preferring peer recommendations and local pilot studies as *** our case illustration,we found that the availability of evidence from comprehensive formative evaluation studies was viewed by stakeholders as positively contributing to program implementation quality and sustainability over ***/Value:We use a real-world"case illustration"of a complex initiative in a large,diverse school district to illustrate how current policies and expectations regarding evidence support for educational programs is filtered through multiple agendas and personal needs of key ***,evaluators acquire nontraditional roles that go beyond routine execution of rigorous *** these factors,we offer recommendations for fostering more meaningful and objective interpretations and usage of evidence by local stakeholders.

关键词： evidence of effectiveness program evaluation technology integration

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Multi-objective optimisation with hybrid machine learning strategy for complex catalytic processes

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energy and AI 2022年第1期7卷 120-130页

作者： Xin Yee Tai raffaella Ocone steven D.r.Christie Jin Xuan Department of Chemical engineering Loughborough UniversityLoughboroughLE113TUUK School of engineering&Physical Science Heriot-Watt UniversityEdinburghEH144ASUK Department of Chemistry Loughborough UniversityLoughboroughLE113TUUK

Catalytic chemical processes such as hydrocracking,gasification and pyrolysis play a vital role in the renewable energy and net zero *** to the complex and non-linear behaviours during operation,catalytic chemical processes require a powerful modelling tool for prediction and optimisation for smart operation,speedy green process routes discovery and rapid process ***,challenges remain due to the lack of an effective modelling and optimisation toolbox,which requires not only a precise analysis but also a fast ***,we propose a hybrid machine learning strategy by embedding the physics-based continuum lumping kinetic model into the data-driven artificial neural network *** hybrid model is adopted as the surrogate model in the multi-objective optimisation and demonstrated in the benchmarking of a hydrocracking *** results show that the novel hybrid surrogate model exhibits the mean square error less than 0.01 by comparing with the physics-based simulation *** well-trained hybrid model was then integrated with non-dominated-sort genetic algorithm(NSGA-II)as the surrogate model to evaluate and optimise the yield and selectivity of the hydrocracking *** Pareto front from the multi-objective optimisation was able to identify the trade-off curve between the objective functions which is essential for the decision-making during process *** work indicates that adopting the hybrid machine learning strategy as the surrogate model in the multi-objective optimisation is a promising approach in various complex catalytic chemical processes to enable an accurate computation as well as a rapid optimisation.

关键词： Hybrid surrogate model Hybrid machine learning Multi-objective optimisation Catalytic chemical process

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Appendectomy and Clostridium difficile colitis:relationships revealed by clinical observations and immunology

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World Journal of Gastroenterology 2013年第34期19卷 5607-5614页

作者： Nathan L Sanders r randal Bollinger ryan Lee steven Thomas William Parker Department of Surgery Duke University Medical Center

Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the *** advances have been made despite long standing clinical observations that the appendectomy is a safe and effective ***,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(***)-associated colitis,and probably other diseases associated with an altered *** the same time,appendectomy does not apparently put patients at risk for an initial onset of ***-associated *** clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of ***-associated ***,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics.

关键词： Appendectomy Clostridium difficile Colitis Diarrheal illness Vermiform appendix

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