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Regulation of drug metabolism and toxicity by multiple factors of genetics,epigenetics,lncRNAs,gut microbiota,and diseases:a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations(MDO)

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Acta Pharmaceutica Sinica B 2017年第2期7卷 241-248页

作者： Ai-Ming Yu Magnus Ingelman-Sundberg nathan j.Cherrington Lauren M.Aleksunes Ulrich M.Zanger Wen Xie Hyunyoung jeong Edward M.Morgan Peter j.Turnbaugh Curtis D.Klaassen Aadra P.Bhatt Matthew R.Redinbo Pengying Hao David j.Waxman Li Wang Xiao-bo Zhong Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California at Davis Department of Physiology and Pharmacology Karolinska Institutet Department of Pharmaceutical Sciences College of PharmacyUniversity of Arizona Department of Pharmacology and Toxicology School of PharmacyRutgers University Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Eberhard Karls University Center of Pharmacogenomics and Department of Pharmaceutical Sciences School of PharmacyUniversity of Pittsburgh Department of Pharmacy Practice School of PharmacyUniversity of Illinois at Chicago Department of Pharmacology School of MedicineEmory University Department of Microbiology and Immunology and the George William Hooper Research Foundation University of California at San Francisco Department of Environmental and Occupational Health Sciences University of Washington Department of Chemistry University of North Carolina at Chapel Hill Department of Biology and Bioinformatics Program Boston University Department of Physiology and Neurobiology University of Connecticut Department of Pharmaceutical Sciences School of PharmacyUniversity of Connecticut

Variations in drug metabolism may alter drug efficacy and cause toxicity;better understanding of the mechanisms and risks shall help to practice precision medicine.At the 21 st International Symposium on Microsomes and Drug Oxidations held in Davis,California,USA,in October 2-6,2016,a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity,and discussed potential implications to personalized medications.A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption,distribution,metabolism,and excretion(ADME) and drug response.Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented.In addition,the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed.These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

关键词： Drug metabolism and toxicity Genetics Epigenetics Gut microbiota Long non-coding RNAs Disease Personalized medication

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运用Sensewear臂环和饮食日记加强青少年的能量平衡知识和积极性（英文）

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journal of Sport and Health Science 2014年第4期3卷 326-332页

作者： Senlin Chen Xihe Zhu Gregory j.Welk Youngwon Kim jungmin Lee nathan F.Meier Department of Kinesiology Iowa State University255 Forker BuildingAmes.IA 50011USA Department of Movement Sciences Old Dominion University.NorfolkVA 23529.USA

目的:对青少年进行能量平衡教育对于有效控制体重至关重要。本研究使用Sensewear臂环和饮食日记来加强青少年的能量平衡知识和积极性。方法:共90名六年级学生被随机分为试验组(n=46)和对照组(n=44),前者连续7天佩戴Sensewear臂环并记饮... 详细信息

目的:对青少年进行能量平衡教育对于有效控制体重至关重要。本研究使用Sensewear臂环和饮食日记来加强青少年的能量平衡知识和积极性。方法:共90名六年级学生被随机分为试验组(n=46)和对照组(n=44),前者连续7天佩戴Sensewear臂环并记饮食日记,后者没有任何行动。两组成员受试前后测量其能量平衡知识、情境兴趣及体重。跟踪记录试验组的动机成果、能量消耗和能量摄入。结果:随着时间的推移,受试者能量平衡知识显著增加,情境兴趣保持稳定(总体兴趣爱好除外),但这些变化没有给试验组带来益处。情境兴趣和动机努力与能量消耗、能量摄入和能量平衡相关。结论:通过Sensewear臂环和饮食日记能追踪能量消耗,对加强青少年的能量平衡知识有积极作用,但作用效果有限。将这两种方法作为教育手段,并结合专注、系统的教育方法有望提高青少年的能量平衡知识和积极性,并促进其形成能量平衡的生活方式。

关键词：能量平衡青少年知识饮食日记教育技术控制体重生活方式

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Photochemistry of chrysene adsorbedon several types of particle

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journal of Environmental Sciences 1995年第2期7卷 233-239页

作者： Zhong jinxian Mauldin R. F. Dunstan , T. D. T ,sanders, j. K. , Hipps, A. D. , Wehry, E. L. , Mamantov, G(Departrnent of Chemistry , University of Tennessee , Knoxville , TN37996 , USA) Dept of Chemistry Univ of Tennessee Knoxville TN USA United States

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关键词： photochemistry chrysene half-lives particles.

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Mastabol induced acute cholestasis: A case report

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World journal of Hepatology 2013年第3期5卷 133-136页

作者： Brett M Hymel David W Victor Luis Alvarez nathan j Shores Luis A Balart Department of Gastroenterology Louisiana State University School of Medicine Department of Gastroenterology and Hepatology Tulane University School of Medicine

A 26-year-old male presented with three weeks of jaundice after the self-initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3one propionate)]. He reported dark urine, light stools, and pruritus. He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL, alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine aminotransferase were 70 units/L and 117 units/L respectively. A working diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia consistent with acute drug induced cholestasis. The patient' s clinical symptoms resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized. Anabolic steroids with 17 alpha carbon substitutions have been associated with a bland variety of cholestatic injury with little hepatocellular injury. Cholestasis, under these circumstances, may be secondary to the binding of drugs to canalicular membrane transporters, accumulation of toxic bile acids from canalicular pump failure, or genetic defects in canalicular transport proteins. Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups at the 17 carbon position. As such, it has been reported to have little potential toxic effects on the liver. This is the first known reported case of Mastabolinduced cholestatic liver injury. It highlights the need for physicians to consider such widely available substances when faced with hepatic injury of unclear etiology.

关键词： Cholestatic Mastabol Hepatic Anabolic Steroids

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Maize Carbohydrate Partitioning Defective33 Encodes an MCTP Protein and Functions in Sucrose Export from Leaves

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Molecular Plant 2019年第9期12卷 1278-1293页

作者： Thu M.Tran Tyler j.McCubbin Saadia Bihmidine Benjamin T.julius R.Frank Baker Martin Schauflinger Clifford Weil nathan Springer Paul Chomet Ruth Wagner jeff Woessner Karen Grote jeanette Peevers Thomas L.Slewinski David M.Braun Division of Biological Sciences’Interdisciplinary Plant Group Missouri Maize CenterUniversity of MissouriColumbiaMO 65211USA Division of Plant Sciences University of MissouriColumbiaMO 65211USA Electron Microscopy Core Facility University of MissouriColumbiaMO 65211USA Department of Agronomy Purdue UniversityWest LafayetteIN 47907USA Department of Plant and Microbial Biology University of MinnesotaSaint PaulMN 55108USA NRGene Inc. 8910 University Center Lane\r\n S u ite 400San DiegoCA 92122USA Bayer Crop Science ChesterfieldMO 63017USA National Key Laboratory for Plant Cell Technology Agricultural Genetics InstituteHanoiVietnam

To sustain plant growth,development,and crop yield,sucrose must be transported from leaves to distant parts of the plant,such as seeds and roots.To identify genes that regulate sucrose accumulation and transport in maize(Zea mays),we isolated carbo/iydrafe part/f/ofi/ngf defecf/Ve33(cpd33),a recessive mutant that accumulated excess starch and soluble sugars in mature leaves.The cpd33 mutants also exhibited chlorosis in the leaf blades,greatly diminished plant growth,and reduced fertility.Cpd33 encodes a protein containing multiple C2 domains and transmembrane regions.Subcellular localization experiments showed the CPD33 protein localized to plasmodesmata(PD),the plasma membrane,and the endoplasmic reticulum.We also found that a loss-of-function mutant of the CPD33 homolog in Arabidopsis,QUIRKY,had a similar carbohydrate hyperaccumulation phenotype.Radioactively labeled sucrose transport assays showed that sucrose export was significantly lower in cpd33 mutant leaves relative to wild-type leaves.However,PD transport in the adaxial-abaxial direction was unaffected in cpd33 mutant leaves.Intriguingly,transmission electron microscopy revealed fewer PD at the companion cell-sieve element interface in mutant phloem tissue,providing a possible explanation for the reduced sucrose export in mutant leaves.Collectively,our results suggest that CPD33 functions to promote symplastic transport into sieve elements.

关键词： carbohydrate accumulation companion cells phloem, plasmodesmata sieve elements symplastictransport

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Studies on nonlinear loss and laser dynamics:from multiwavelength CW lasing to multi-pulsing transition

Studies on nonlinear loss and laser dynamics:from multiwavel...

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2010亚洲光电子会议光电器件及其集成分会场

作者： j.nathan Kutz P.K.A.Wai Department of Applied Mathematics University of Washington Photonics Research Centre Department of Electronics and Information EngineeringThe Hong Kong Polytechnic University

We develop a simple iterative model to simulate a laser with homogeneous gain and intensity dependent loss. Simulation results show that a laser with homogenous gain can operate at multiple wavelengths if the intensity-dependent loss exhibits saturable transmitter characteristics. Our results also show that for nonlinear losses that have both saturable transmitter and saturable absorber characteristics, such as arises from nonlinear optical loss mirrors (NOLM) or nonlinear polarization rotation (NPR), the multiwavelength output power spectrum can become very flat. The laser can also exhibit periodic and chaotic behaviors. We find that the same theoretical model can also be used to describe multi- pulsing dynamics of mode-locked lasers when the cavity energy increases. Near the multi-pulsing transitions, both periodic and chaotic behavior can be observed as operating states of the laser cavity. Our iterative model provides a simple geometrical description of the entire multi-pulsing transition behavior as a function of increasing cavity energy. The model captures all the key features observed in experiments, including the periodic and chaotic mode-locking regions, and further provides valuable insight into laser cavity engineering for maximizing performance.

关键词： Multiwavelength laser Nonlinear loss Mode-locking Multi-pulsing Discrete model Chaos

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Machine learning in data abstraction: A computable phenotype for sepsis and septic shock diagnosis in the intensive care unit

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World journal of Critical Care Medicine 2019年第7期8卷 120-126页

作者： Prabij Dhungana Laura Piccolo Serafim Arnaldo Lopez Ruiz Danette Bruns Timothy j Weister nathan jerome Smischney Rahul Kashyap Department of Anesthesiology and Perioperative Medicine Mayo ClinicRochesterMN 55905United States Multidisciplinary Epidemiology and Translational Research in Intensive Care Mayo ClinicRochesterMN 55905United States Department of Medicine Division of Pulmonary and Critical Care MedicineMayo ClinicRochesterMN 55905United States Anesthesia Clinical Research Unit Mayo ClinicMN 55905United States

BACKGROUND With the recent change in the definition(Sepsis-3 Definition)of sepsis and septic shock,an electronic search algorithm was required to identify the cases for data automation.This supervised machine learning method would help screen a large amount of electronic medical records(EMR)for efficient research purposes.AIM To develop and validate a computable phenotype via supervised machine learning method for retrospectively identifying sepsis and septic shock in critical care patients.METHODS A supervised machine learning method was developed based on culture orders,Sequential Organ Failure Assessment(SOFA)scores,serum lactate levels and vasopressor use in the intensive care units(ICUs).The computable phenotype was derived from a retrospective analysis of a random cohort of 100 patients admitted to the medical ICU.This was then validated in an independent cohort of 100 patients.We compared the results from computable phenotype to a gold standard by manual review of EMR by 2 blinded reviewers.Disagreement was resolved by a critical care clinician.A SOFA score≥2 during the ICU stay with a culture 72 h before or after the time of admission was identified.Sepsis versions as V1 was defined as blood cultures with SOFA≥2 and Sepsis V2 was defined as any culture with SOFA score≥2.A serum lactate level≥2 mmol/L from 24 h before admission till their stay in the ICU and vasopressor use with Sepsis-1 and-2 were identified as Septic Shock-V1 and-V2 respectively.RESULTS In the derivation subset of 100 random patients,the final machine learning strategy achieved a sensitivity-specificity of 100%and 84%for Sepsis-1,100%and 95%for Sepsis-2,78%and 80%for Septic Shock-1,and 80%and 90%for Septic Shock-2.An overall percent of agreement between two blinded reviewers had a k=0.86 and 0.90 for Sepsis 2 and Septic shock 2 respectively.In validation of the algorithm through a separate 100 random patient subset,the reported sensitivity and specificity for all 4 diagnoses were 100%-100%each.CONCLUSION Supervised machine learning for i

关键词： Machine learning Computable phenotype Critical care Sepsis Septic shock

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Helical Covalent Polymers with Unidirectional Ion Channels as Single Lithium-Ion Conducting Electrolytes

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CCS Chemistry 2021年第12期3卷 2762-2770页

作者： Yiming Hu nathan Dunlap Hai Long Hongxuan Chen Lacey j.Wayment Michael Ortiz Yinghua jin Abdulrahiman Nijamudheen jose L.Mendoza-Cortes Se-hee Lee Wei Zhang Department of Chemistry University of Colorado BoulderBoulderCO 80309 Department of Mechanical Engineering University of Colorado BoulderBoulderCO 80309 National Renewable Energy Laboratory GoldenCO 80401 Department of Chemical Engineering and Materials Science Michigan State UniversityEast LansingMI 48824

Single-ion conducting polymer electrolytes have attracted great attention as safe alternatives to liquid electrolytes in high energy density lithium-ion batteries.Herein,we report the first example of a crystalline anionic helical polymer as a single lithium-ion conducting solid polymer electrolyte(SPE).Single-crystal X-ray analysis shows that the polymer folds into densely packed double helices,with bundles of unidirectional negatively charged channels formed that can facilitate lithium-ion transportation.

关键词： helical covalent polymer spiroborate single-ion conducting electrolyte

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包装工业用的刚性容器铝合金薄板

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轻合金加工技术 1990年第9期18卷 16-25页

作者： R.E.sanders jr. D.j.Lege 张君尧

在美国,包装工业目前是铝薄板的最大用户。刚性容器铝合金薄板由于有极好的冶金特性和可回收性,因而广泛地用于制造啤酒和饮料罐。通过对罐结构、合金和加工工艺等方面的综合改进,有可能成功地制造出更轻的铝罐。本文讨论为了生产轻重... 详细信息

在美国,包装工业目前是铝薄板的最大用户。刚性容器铝合金薄板由于有极好的冶金特性和可回收性,因而广泛地用于制造啤酒和饮料罐。通过对罐结构、合金和加工工艺等方面的综合改进,有可能成功地制造出更轻的铝罐。本文讨论为了生产轻重量罐体和罐盖,得到有足够强度和成形性能的薄板,而提出的一些重要的冶金方面的设想。比较了3004和5182舍金的显微组织、加工硬化程度和应变速率敏感性。虽然实际测量罐坯料固有的成形性能是很困难的,但是提出了力学性能与成形性能之间的关系。

关键词：刚性容器铝合金薄板

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The Efficacy of Psychosocial Interventions for Adults in Contexts of Ongoing Man-Made Violence—A Systematic Review

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Health 2014年第6期6卷 504-516页

作者： Kaz de jong jeroen W. Knipscheer nathan Ford Rolf j. Kleber Department of Clinical and Health Psychology Utrecht University Utrecht The Netherlands Médecins sans Frontières Doctors without Borders (Amsterdam Office) Amsterdam The Netherlands Médecins sans Frontières Doctors without Borders (International Office) Geneva Switzerland

Compared to psychosocial programs implemented in post-conflict settings those executed in areas of ongoing conflicts may have different effects. Their evidence of efficacy has never been systematically reviewed. We searched PubMed, PsychInfo and the Dutch Tropical Institute Literature Portal from inception to31 january 2013 to identify studies on community-oriented psychosocial and psychiatric/clinical services for adults during ongoing manmade conflict or its direct aftermath. Of 6358 articles screened, 16 met our inclusion criteria. The interventions varied from psycho-educational to psychotropic drugs. The review is presented using outcome indicators such as PTSD, anxiety, depression, physical health, functioning and well being. A substantial improvement of some outcome was found though the small number of studies and their heterogeneity did not justify strong conclusions. PTSD symptoms improved significantly by treatments that included exposure (such as narrative exposure therapy). A number of studies (eight) showed notable improvement of the client’s functioning through counseling interventions. Depression and anxiety both improved considerably using that culturally adapted interventions (two studies), whereas non-culturalized interventions did not. We found a notable lack of studies on the efficacy of medication and on preferred western, evidence-based interventions for PTSD such Eye Movement Desensitization. To measure outcomes only two studies applied locally-developed diagnostic labels and validated instruments. Future research should encourage the use of robust research methods that are culturally valid, including mixed-methods research to combine measurable outputs with qualitative research aimed at improved understanding from the client’s perspective.

关键词： Psychosocial Mental Health Programmes Systematic Review Conflict Post-Conflict War Violence PTSD

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