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An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads:Experimental studies and molecular dynamics analysis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2669-2684页

作者： Jamie Anne Lugtu-Pe Xuning Zhang Sako Mirzaie Hao Han R.Chang Nour AL-Mousawi Kuan Chen Yongqiang Li Anil Kane Daniel Bar-Shalom Xiao Yu Wu Advanced Pharmaceutics and Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoToronto M5S 3M2Canada Candoo Pharmatech Company Inc. Mississauga L5N 5M1Canada Department of Pharmacy University of CopenhagenCopenhagen DK-2100Denmark Patheon by Thermo Fisher Scientific Toronto Region Operations(TRO)Mississauga L5N 3X4Canada

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

关键词： Controlled release amorphous solid dispersion Poorly soluble drug Internal recrystallization Membrane-reservoir coated beads Molecular dynamics simulation Effect of pore formers Terpolymer nanogel Drug-polymer interactions

Beware the Demon of Love Jihad! The Gendered and Sexual Abjectification of Muslim Masculinities by Hindu Nationalists on Twitter

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Journal of Sociology Study 2024年第3期14卷 157-170页

作者： Zeinab Farokhi university of toronto mississauga OntarioCanada

In this paper,I examine the Twitter accounts of right-wing extremist groups(RWEGs)in India,arguing that the abjectification of Muslim masculinities is central to the narratives of Hindu supremacist groups.The abjectification process on Twitter serves as a rhetorical device to:a)criticize and problematize Muslim masculinities;b)idealize and glorify Hindu and white masculinities;c)promote Hindu and white masculine nationalist projects;and d)unify Hindu supremacists against Muslim others.By analyzing the gender ideologies expressed implicitly or explicitly on the Twitter accounts of RWEGs,and using the“Love Jihad”conspiracy case as a focal point,I demonstrate how the abjectification of Muslim masculinities is constructed in opposition to the idealized Hindu masculinities.This study highlights the intersection of gender and nationalism in the digital discourse of Hindu supremacist groups,offering insights into the mechanisms through which social media platforms are used to reinforce and propagate Islamophobic ideologies.

关键词： Muslim masculinities Hindu supremacy conspiracy theory social media right-wing extremism

How the physical inactivity is affected by social-, economic- and physical-environmental factors: an exploratory study using the machine learning approach

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International Journal of Digital Earth 2023年第1期16卷 2503-2521页

作者： Kangjae Lee Jue Wang Joon Heo Department of Location-Based Information System Kyungpook National UniversitySangju-siGyeongsangbukdoRepublic of Korea Department of Geography Geomatics and EnvironmentUniversity of Toronto MississaugaMississaugaCanada Department of Civil and Environmental Engineering Yonsei UniversitySeoulRepublic of Korea

Previous studies have utilized regression models to investigate the impact of environmental factors on physical activity.However,such approaches are inadequate for data-driven analysis seeking to identify robust associations from the intricate and multi-variable interactions between physical activity and environmental factors.With the emergence of the concept of the exposome,which encompasses the totality of exposures,this paper explores machine learning models for predicting the percentage of physical inactivity in U.S.counties,while considering 28 social-,economic-,and physical-environmental factors.The aim of this study is to address the research gap and gain insight into the complex associations between environmental exposures and physical activity.Five machine learning models were tested,and the performances were compared to select the best classifier for further investigation.This study used data from the Behavioral Risk Factor Surveillance System(BRFSS)of the Centers for Disease Control and Prevention.The mean population of all counties was 102,841,and the mean percentage of population below 18 years was 22.3%.The partial dependence plot analysis indicated that only one feature–bachelor’s degree–exhibited a close-to-linear relationship with physical inactivity.Motor-vehicle crash death rate and mean temperature showed nonlinear and non-monotonic relationships with the predicted percentage of physical inactivity.

关键词： Physical inactivity environmental effects machine learning GIS

Animated images in the analysis of zebrafish behavior

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Current Zoology 2017年第1期63卷 35-44页

作者： Robert GERLAI Department of Psychology University of Toronto Mississauga 3359 Mississauga Road North Rm CCT4004Mississauga Ontario Canada LSL 1C6

This invited review is based upon a recent oral paper I presented at the Virtual Reality Symposiumof the 34th International Ethological Conference （2015, Cairns, Australia）, and as such it describesstudies conducted mainly in my own laboratory. It reviews how we utilized visual stimuli for induc-ing behavioral responses in the zebrafish with a focus on shoaling, group forming behavior. Thezebrafish is gaining increasing popularity in neuroscience. With this interest, its behavior is alsomore frequently studied. One of the many advantages of the zebrafish over traditional laboratoryrodents is that this species is diurnal, and it relies heavily upon its visual system. Thus, similarly toour own species, zebrafish respond to visual stimuli in a robust and easily quantifiable manner. Forthe past decade, we have been exploring how to use such visual stimuli, and have developed nu-merous paradigms with which we can induce and quantify a variety of behavioral responses,including shoaling. This review summarizes some of these studies, and discusses questions includ-ing whether one should use live fish as stimulus, whether and how one could present animated（moving images） of fish, and how one could optimize a range of stimulus presentation parametersto elicit the most robust responses in zebrafish. Although the zebrafish is a relative newcomer inethology and behavioral neuroscience, and although many of our findings only represent the firststeps in this research, our results suggest that the behavioral analysis of the zebrafish will have animportant place in biomedical research.

关键词： alcohol, animated images, high-throughput screening, learning and memory, schooling fish, shoaling, social behavior,zebra fish.

AQUEOUS STABLE FREE RADICAL POLYMERIZATION PROCESSES

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Chinese Journal of Polymer Science 2004年第4期22卷 309-312页

作者： Andrea R. Szkurhan Michael K. Georges university of toronto at mississauga 3359 Mississauga Road North South Building Mississauga Ontario L5L 1C6University of Toronto at Mississauga 3359 Mississauga Road North South Building Mississauga Ontario L5L 1C6

An overview of aqueous polymerizations, which include emulsion, miniemulsion and suspension polymerizations, under stable free radical polymerization (SFRP) conditions is presented. The success of miniemulsion and suspension SFRP polymerizations is contrasted with the difficulties associated with obtaining a stable emulsion polymerization. A recently developed unique microprecipitation technique is referenced as a means of making submicron sized particles that can be used to achieve a stable emulsion SFRP process.

关键词： Stable free radical polymerization Living-radical polymerization Aqueous polymerization Miniemulsion polymerization Emulsion polymerization Suspension polymerization

A Method to Reduce the Lehmer Measure in a Multi-Term Machin-Like Formula for π

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Open Journal of Applied Sciences 2022年第8期12卷 1477-1493页

作者： Sanjar M. Abrarov Rehan Siddiqui Rajinder K. Jagpal Brendan M. Quine Epic College of Technology Mississauga Canada York university Toronto Canada

Previously we have proposed a new method of transforming quotients into integer reciprocals in the Machin-like formulas for π. As a further development, here we show how to generate a multi-term Machin-like formula f... 详细信息

关键词： Constant Pi Machin-Like Formula Lehmer’s Measure

Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study

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Neural Regeneration Research 2022年第7期17卷 1582-1587页

作者： Xiaoyue Li Xuan Mo Tao Liu Robin Shao Kayla Teopiz Roger S.McIntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Laboratory of Emotion and Cognition The Affiliated Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Canadian Rapid Treatment Center of Excellence MississaugaONCanada Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversityHealth NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoONCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder.In preclinical models of neurological and psychiatric diseases,Lycium barbarum polysaccharide(LBP)extracted from Goji berries had antidepressant effects including but not limited to anti-oxidative and anti-inflammatory properties.However,the effect of LBP on subthreshold depression is unclear.To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents,we conducted a randomized,double-blind,placebo-controlled trial(RCT)with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical university.The participants were randomly assigned to groups where they received either 300 mg LBP(LBP group,n=15,3 boys and 12 girls aged 15.13±2.17 years)or a placebo(placebo group,n=14,2 boys and 12 girls aged 15±1.71 years)for 6 successive weeks.Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale(HAMD-24)scores relative to the baseline and a higher remission rate(HAMD-24 total score≤7)at 6 weeks compared with the placebo group.Scores on the Beck Depression Inventory-II(BDI-II),Pittsburgh Sleep Quality Index(PSQI),Kessler Psychological Distress Scale(Kessler),and Screen for Child Anxiety-Related Emotional Disorders(SCARED)were similar between the LBP and placebo groups.No side effects related to the intervention were reported in either group.These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression.Furthermore,LBP was well tolerated with no treatment-limiting adverse events.Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression.This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical university(Guangzhou,China;approval No.L2019-08)on April 4,2019 and

关键词： adolescents efficacy Goji berry Lycium barbarum polysaccharide randomized clinical trial safety subthreshold depression tolerance

Universal Enveloping Algebras of Simple Symplectic Anti-Jordan Triple Systems

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Algebra Colloquium 2015年第2期22卷 281-292页

作者： Marina Tvalavadze university of toronto (mississauga Campus) Mathematical and Computational Sciences3359 mississauga Rd. N Mississauga ON L5L 1C6 Canada

In this work we axe concerned with the universal associative envelope of a finite-dimensional simple symplectic anti-Jordan triple system （AJTS）. We prove that if T is a triple system as above, then there exists an associative algebra U（T） and an injective homomorphism ε ： T→ U（T）, where U（T） is an AJTS under the triple product defined by （a, b, c） = abc- cba. Moreover, U（T） is a universal object with respect to such homomorphisms. We explicitly determine the PBW-basis of U（T）, the center Z（U（T）） and the Gelfand-Kirillov dimension of U（T）.

关键词： anti-Jordan triple systems universal enveloping algebras central elements,PBW-bases

Propofol enhances the field excitatory postsynaptic potentials in CA1 hippocampal slices of young and aged mice

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Chinese Medical Journal 2014年第1期127卷 137-141页

作者： Yin Yiqing William J Middleton Carlos M. Florez Peter L. Carlen Hossam EI-Beheiry Department of Anesthesia Peking University China-Japan Friendship Hospital Beijing 100029 China Department of Anesthesia Toronto Westem Hospital University ofToronto University Health Network Toronto Canada toronto Western Research Institute University of Toronto TorontoCanada Department of Anesthesia Trillium Health Centre MississaugaOntario Canada

Background Increasing age was shown to decrease the requirements for propfol.However,the mechanisms of ageing-induced potentiation of anesthetic actions have not been clearly explored.The aim of this study is to compare the effects of propofol on the field excitatory postsynaptic potentials （fEPSPs） in hippocampal slices of young and aging mice.Methods Brain slices were prepared from C57BL6 male young （2 months） and aging （＞12 months） mice.The dendritic field excitatory postsynaptic potential was recorded from the CA1 stratum radiatum using patch clamp electrophysiological methods.A bipolar concentric stimulating electrode was placed along the Schaffer collateral for othodromic stimulation.The effects of clinically-relevant concentrations of propofol were studied in the young and ageing mouse tissues.Results Propofol application increased the orthodromically evoked fEPSP produced in slices taken from young and older animals.A striking feature in the I/O relationship was the decreased enhancement of the fEPSPs by propofol in slices from older mice.A clinically relevant concentration of propofol,10 μmol/L,showed more significant enhancement in amplitude and area under the curve （AUC） of fEPSP in young compared to tissues from older mice （amplitude：young （24.9±3.4）％,old （4.6±1.6）％; AUC young （30.6±5.4）％,old （2.1±1.7）％）.There was no statistically significant difference between the paired-pulse facilitation （PPF） ratios calculated for the responses obtained in tissues from young mice.In slices from older mice,in the presence of 10 μmol/L propofol,PPF was decreased and returned to baseline after washout （baseline 1.21±0.01,propofol：1.16±0.01）.Bicuculline （15 μmol/L） blocked the enhancement of propofol on fEPSP in tissues from young and old mice.Conclusion The fEPSP of slices from aging mice demonstrates diminished sensitivity to the enhancing actions of propofol.

关键词： propofol field excitatory postsynaptic potentials CA1 hippocampal slice aging patch clamp