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Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma

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Neural Regeneration Research 2023年第4期18卷 840-848页

作者： Devaraj Basavarajappa Vivek Gupta Nitin Chitranshi Roshana Vander Wall Rashi Rajput kanishka pushpitha Samridhi Sharma Mehdi Mirzaei Alexander Klistorner Stuart L.Graham Department of Clinical Medicine Faculty of MedicineHealth and Human SciencesMacquarie UniversityNorth RydeSydneyNSWAustralia

Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous *** role of S1PR signaling in neurodegenerative conditions is still largely *** is a specific modulator of S1P1 and S1P5 receptors,an immunosuppressant drug for managing secondary progressive multiple *** investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate ***-specific deletion of sphingosine-1-phosphate receptor(S1PR1)was carried out by expressing ***-Cre recombinase under Syn1 promoter in S1PR1mice to define the role of S1PR1 in *** retinal electrophysiological responses,along with histological and immunofluorescence analysis of the retina and optic nerve tissues,indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury ***,siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve *** treatment also reduced microglial activation and reactive gliosis along the visual *** results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the ***-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of *** summary,our data demonstrated that S1PR1signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma,and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory *** findings s

关键词： glaucoma intraocular pressure neurodegeneration neuroprotection optic nerve injury retinal ganglion cells siponimod sphingosine-1-phosphate

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Amyloid-beta peptide neurotoxicity in human neuronal cells is associated with modulation of insulin-like growth factor transport, lysosomal machinery and extracellular matrix receptor interactions

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Neural Regeneration Research 2020年第11期15卷 2131-2142页

作者： Liting Deng Paul AHaynes Yunqi Wu Ardeshir Amirkhani Karthik Shantharam Kamath Jemma XWu kanishka pushpitha Veer Gupta Stuart Graham Vivek KGupta Mehdi Mirzaei Department of Molecular Sciences Faculty of Science and EngineeringMacquarie UniversitySydneyNSWAustralia Australian Proteome Analysis Facility(APAF) Macquarie UniversitySydneyNSWAustralia Faculty of Medicine and Health Sciences Macquarie UniversitySydneyNSWAustralia School of Medicine Deakin UniversityGeelongVICAustralia

Extracellular deposits of the amyloid-beta peptide(Aβ) are known as the main pathological hallmark of Alzheimer's disease. In Alzheimer's disease, neurons are injured and die throughout the brain, a process in which Aβ neurotoxicity is considered to play an important role. However, the molecular mechanisms underlying Aβ toxicity that lead to neurodegeneration are not clearly established. Here we have elucidated the molecular pathways and networks which are impacted by Aβ in neurons using SH-SY5Y human neuroblastoma cells as a model. These cells were treated with Aβ_(1–42) peptides to study changes in biochemical networks using tandem mass tag labeled quantitative proteomic technique followed by computational analysis of the data. The molecular impacts of Aβ on cells were evident in a time-and dose-dependent manner, albeit the duration of treatment induced greater differential changes in cellular proteome compared to the effects of concentration. Aβ induced early changes in proteins associated with lysosomes, collagen chain trimerization and extracellular matrix receptor interaction, complement and coagulation cascade, oxidative stress induced senescence, ribosome biogenesis, regulation of insulin-like growth factor transport and uptake by insulin-like growth factor-binding protein. These novel findings provide molecular insights on the effects of Aβ on neurons, with implications for better understanding the impacts of Aβ on early neurodegeneration in Alzheimer's disease pathology.

关键词： Alzheimer's disease amyloid lysosomes neurodegeneration oxidative stress proteomics ribosome SH-SY5Y cells

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High performance in Zintl thermoelectrics via reduction in crystal field splitting energy

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Science China Materials 2024年第10期 3424-3425页

作者： Anustoop Das kanishka Biswas New Chemistry Unit School of Advanced Materials and International Centre for Materials Science Jawaharlal Nehru Centre for Advanced Scientific Research(JNCASR)

Sustainable thermoelectric materials open an avenue of emission-free as well as fast-responding recycling of energy in terms of heat to *** efficiency （η） of such conversion is primarily guided by the dimensionless thermoelectric figure of merit （zT）,which depends on parameters like Seebeck coefficient （S）,electrical conductivity （σ）,and thermal conductivity（κ） at a given temperature （T）,which are adversely interrelated to each other （zT=S2σT/κ）[1,2].

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Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients

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World Journal of Clinical Oncology 2024年第7期15卷 848-858页

作者： Naveed Syed Ashish Vittalrao Chintakuntlawar Deepti Vilasini Aisha Mohamed Al Salami Riad Al Hasan Imrana Afrooz kanishka Uttam Chandani Ashok Uttam Chandani Aref Chehal Department of Hematology and Oncology Sheikh Shakbout Medical CityAbu Dhabi 11001United Arab Emirates Department of Oncology Mayo ClinicRochesterNY 790339United States Department of Oncology Sheikh Shakbout Medical CityAbu Dhabi 11001United Arab Emirates Clinical Research Sheikh Shakbout Medical CityAbu Dhabi 11001United Arab Emirates Department of Internal Medicine Landmark Medical CenterRhode IslandRI 02895United States

BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast *** are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-***,data on these mutations and PARPi use in the Middle East are *** To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian *** This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for *** adult patients participated in at least four visits to the oncology service at our center between August 2021 and May *** were summarized using descriptive statistics and compared using counts and *** to treatment was assessed using Response Evaluation Criteria in Solid Tumors *** Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD *** mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed ***,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,*** treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained *** Lower testing rates but higher BRCA mutations in breast cancer were *** reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.

关键词： Homologous recombination repair BRCA1 BRCA2 Homologous recombination deficiency Ovarian cancer Breast cancer Poly(ADP-ribose)polymerase inhibitors Olaparib DNA double-strand breaks

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A PLS-SEM Based Approach: Analyzing Generation Z Purchase Intention Through Facebook’s Big Data

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Big Data Mining and Analytics 2023年第4期6卷 491-503页

作者： Vikas Kumar Preeti Shaiku Shahida Saheb Sunil Kumari kanishka Pathak Jai Kishan Chandel Neeraj Varshney Ankit Kumar Humanities and Management Department Dr.B.R.Ambedkar National Institute of Technology JalandharJalandhar 144027India Department of Commerce and Business Administration Kanya Maha Vidyalaya(KMV)Jalandhar 144004India Mittal School of Business Lovely Professional UniversityPhagwara 144402India Government College for Women Indra Gandhi UniversityAteli 123021India Institute of Management Studies Kurukshetra UniversityKurukshetra 136119India Kumar are with the Department of Computer Engineering and Applications GLA UniversityMathura 281406India

The objective of this paper is to provide a better rendition of Generation Z purchase intentions of retail products through *** study gyrated around the favorable attitude formation of Generation Z translating into intentions to purchase retail products through *** role of antecedents of attitude,namely enjoyment,credibility,and peer communication was also *** main purpose was to analyze the F-commerce pervasiveness(retail purchases through Facebook)among Generation Z in India and how could it be materialized effectively.A conceptual fac¸ade was proposed after trotting out germane and urbane *** study focused exclusively on Generation Z *** data were statistically analyzed using partial least squares structural equation *** study found the proposed conceptual model had a high prediction power of Generation Z intentions to purchase retail products through Facebook verifying the materialization of ***,credibility,and peer communication were proved to be good predictors of attitude(R^(2)=0.589)and furthermore attitude was found to be a stellar antecedent to purchase intentions(R^(2)=0.540).

关键词： Facebook enjoyment credibility peer communication attitude intentions to purchase

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Growth Kinetics of Nanocrystals and Nanorods by Employing Small-angle X-ray Scattering (SAXS) and Other Techniques

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Journal of Materials Science & Technology 2008年第4期24卷 615-627页

作者： kanishka BISWAS Neenu VARGHESE C.N.R.Rao Chemistry and Physics of Materials Unit DST Nanoscience Unit and CSIR Centre of Excellence in ChemistryJawaharlal Nehru Centre for Advanced Scientific ResearchJakkur P.O.Bangalore 560064India Solid State and Structural Chemistry UnitIndian Institute of ScienceBangalore 560012India Chemistry and Physics of Materials Unit DST Nanoscience Unit and CSIR Centre of Excellence in ChemistryJawaharlal Nehru Centre for Advanced Scientific ResearchJakkur P.O.Bangalore 560064India

In this article, we report the results of our detailed investigations of the growth kinetics of zero-dimensional nanocrystals as well as one-dimensional nanorods by the combined use of small angel X-ray scattering （SAXS）, transmission electron microscopy （TEM） along with other physical techniques. The study includes growth kinetics of gold nanocrystals formed by the reduction of HAuCl4 by tetrakis（hydroxymethyl） phosphonium chloride in aqueous solution, of CdSe nanocrystals formed by the reaction of cadmium stearate and selenium under solvothermal conditions, and of ZnO nanorods formed by the reaction of zinc acetate with sodium hydroxide under solvothermal conditions in the absence and presence of capping agents. The growth of gold nanocrystals does not follow the diffusion-limited Ostwald ripening, and instead follows a Sigmoidal rate curve. The heat change associated with the growth determined by isothermal titration calorimetry is about 10 kcal·mol^-1 per I nm increase in the diameter of the nanocrystals. In the case of CdSe nanocrystals also, the growth mechanism deviates from diffusion-limited growth and follows a combined model containing both diffusion and surface reaction terms. Our study of the growth kinetics of uncapped and poly（vinyl pyrollidone）（PVP）-capped ZnO nanorods has yielded interesting insights. We observe small nanocrystals next to the ZnO nanorods after a lapse of time in addition to periodic focusing and defocusing of the width of the length distribution. These observations lend support to the diffusion-limited growth model for the growth of uncapped ZnO nanorods. Accordingly, the time dependence on the length of uncapped nanorods follows the L3 law as required for diffusion-limited Ostwald ripening. The PVP-capped nanorods, however, show a time dependence, which is best described by a combination of diffusion （L^3） and surface reaction （L^2） terms.

关键词： Growth kinetics Gold nanocrystals CdSe nanocrystals ZnO nanorods Small angle X-ray scattering Transmission electron microscopy Ostwald ripening and sigmoidal growth

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Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features

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Chinese Journal of Cancer 2013年第6期32卷 303-311页

作者： kanishka Sircar Priya Rao Eric Jonasch Federico A. Monzon Pheroze Tamboli Departments of Pathology and the David H. Koch Center for Applied Research of Genitourinary Cancers The University of Texas MD Anderson Cancer CenterHouston TX 77030 USA Departments of Genitourinary Medical Oncology and the David H. Koch Center for Applied Research of Genitourinary Cancers The University of Texas MD Anderson Cancer CenterHouston TX 77030 USA Department of Pathology and Immunology and Department of Human and Molecular Genetics Baylor College of MedicineHouston TX 77030 USA

Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear-cell and non-clearcell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohistochemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.

关键词：鉴别诊断肾细胞癌症混合分类细胞遗传学肾肿瘤组织学

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Solute manipulation enabled band and defect engineering for thermoelectric enhancements of SnTe

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InfoMat 2019年第4期1卷 571-581页

作者： Zhichao Yao Wen Li Jing Tang Zhiwei Chen Siqi Lin kanishka Biswas Alexander Burkov Yanzhong Pei Interdisciplinary Materials Research Center School of Materials Science and EngineeringTongji UniversityShanghaiChina Jawaharlal Nehru Centre for Advanced Scientific Research(JNCASR) BangaloreIndia Laboratory for Physics of Thermoelements Ioffe InstituteSankt-PetersburgRussia

With years of development, SnTe as a homologue of PbTe has shown great potentialfor thermoelectric applications in p-type conduction, and the most successfulstrategy is typified by alloying for maximizing the valence band *** the known alloy agents, MnTe has been found to be one of the most effectiveenabling a band convergence for an enhancement in electronic performance ofSnTe, yet its solubility of only ~15 at% unfortunately prevents a full optimizationin the valence band structure. This work reveals that additional PbTe alloying notonly promotes the MnTe solubility to locate the optimal valence band structure butalso increases the overall substitutional defects in the material for a substantialreduction in lattice thermal conductivity. In addition, PbTe alloying simultaneouslyoptimizes the carrier concentration due to the cation size effect. These features allenabled by such a solute manipulation synergistically lead to a very high thermoelectricfigure of merit, zT of ~1.5 in SnTe with a 20 at% MnTe and a 30 at% PbTealloying (Sn0.5Mn0.2Pb0.3Te), demonstrating the effectiveness of solute manipulationfor advancing SnTe and similar thermoelectrics.

关键词： band engineering MnTe solubility SnTe thermoelectric

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二阶Newton法训练径向基函数神经网络的算法研究

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计算机研究与发展 2015年第7期52卷 1477-1486页

作者：蔡珣陈智 kanishka Tyagi 于宽李子强朱波山东大学计算机科学与技术学院济南250101 德克萨斯大学阿灵顿分校电子工程系美国阿灵顿76019 山东建筑大学材料科学与工程学院济南250101 山东大学材料科学与工程学院济南250061

提出了一种混合加权距离测量(weighted distance measure,weighted DM)参数的构建和训练RBF(radial basis function)神经网络的两步批处理算法.该算法在引进了DM系数参数的基础上,采用Newton法分别对径向基函数的覆盖参数、均值向量参... 详细信息

提出了一种混合加权距离测量(weighted distance measure,weighted DM)参数的构建和训练RBF(radial basis function)神经网络的两步批处理算法.该算法在引进了DM系数参数的基础上,采用Newton法分别对径向基函数的覆盖参数、均值向量参数、加权距离测度系数以及输出权值进行了优化,并在优化过程中利用OLS(orthogonal least squares)法来求解Newton法的方程组.通过实验数据,不仅分析了Newton法优化的各个参数向量对RBF网络训练的影响,而且比较了混合优化加权DM与RLS-RBF(recursive least square RBF neural network)网络训练算法的收敛性和计算成本.所得到的结论表明整合了优化参数的加权DM-RBF网络训练算法收敛速度比RLS-RBF网络训练算法更快,而且具有比LM-RBF(Levenberg-Marquardt RBF)训练算法更小的计算成本,从而说明OLS求解的Newton法对优化RBF网络参数具有重要应用价值.

关键词：径向基函数神经网络 Hessian矩阵 Newton法正交最小二乘法网络参数优化最优学习因子

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Study on Graphene Based Next Generation Flexible Photodetector for Optical Communication

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Graphene 2018年第2期7卷 9-16页

作者： kanishka Majumder Devesh Barshilia Subimal Majee Academy of Technology Maulana Abul Kalam Azad University of Technology Kolkata India CSIR-Central Electronics Engineering Research Institute (CEERI) Pilani India

We report on the efficient photodetection (PD) properties of graphene based p-i-n photodetector, where all the three layers are either single or multilayer graphene sheets. We report the bandwidth and responsivity performance of the device. This simple structure paves the way for the next generation flexible wireless communication systems. A theoretical model is used to study the carrier distribution and current in a graphene based p-i-n photodetector system.

关键词： Graphene Photodetector Flexible Electronics

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