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Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1885-1902页

作者： Xu Wu Chun Yin Jiang Ma Stella Chai Chunyuan Zhang Sheng Yao onat kadioglu Thomas Efferth Yang Ye Kenneth Kin-Wah To Ge Lin School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between the Chinese University of Hong Kong and Shanghai Institute of Materia Medica Chinese Academy of SciencesHong Kong 999077China State Key Laboratory of Drug Research and Natural Products Chemistry Department Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Pharmaceutical Biology Johannes Gutenberg UniversityMainz 55099Germany School of Pharmacy Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhou 646000China

Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer ***,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug ***,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(***)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active *** metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug *** POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in *** further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated *** results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated *** work also provided scientific evidence for the use of *** in combinational chemotherapy.

关键词： Multidrug resistance ABCB1 Polyoxypregnane Combination chemotherapy Marsdenia tenacissima

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Impact of trading hours extensions on foreign exchange volatility:intraday evidence from the Moscow exchange

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Financial Innovation 2023年第1期9卷 2729-2751页

作者： Michael Frommel Eyup kadioglu Department of Economics Ghent UniversitySint‑Pietersplein 59000 GhentBelgium Investor Compensation Center Capital Markets Board of TurkeyMustafa Kemal MahallesiEskişehir Yolu 8.Km No:15606530 CankayaAnkaraTurkey

Using transaction-level tick-by-tick data of same-and next-day settlement of the Russian Ruble versus the US Dollar exchange rate(RUB/USD)traded on the Moscow Exchange Market during the period 2005–2013,we analyze the impact of trading hours extensions on *** the sample period,the Moscow Exchange extended trading hours three times for the same-day settlement and two times for the next-day settlement of the RUB/USD *** analyze the effect of the implementations,various measures of historical and realized volatility are calculated for 5-and 15-min intraday intervals spanning a period of three months both prior to and following trading hours *** historical volatility measures,we also examine volume and *** apply an autoregressive moving average-autoregressive conditional heteroscedasticity(ARMA-GARCH)model utilizing realized volatility and a trade classification rule to estimate the probability of informed *** extensions of trading hours cause a significant increase in both volatility and volume for further analyzing the reasons behind volatility *** changes mostly occur after the opening of the *** length of the extension has a significant positive effect on realized *** results indicate that informed trading increased substantially after the opening for the rate of same-day settlement,whereas this is not observed for next-day *** trading hours extensions raise opportunities for more transactions and liquidity in foreign exchange markets,they may also lead to higher volatility in the ***,this distortion is more significant at opening and midday.A potential explanation for the increased volatility mostly at the opening is that the trading hours extension attracts informed traders rather than liquidity providers.

关键词： Volatility Trading hours extension Foreign exchange market Informed trading Volume Spread Market overlap Information flow

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Mechanical behaviour of adhesively single lap joint under buckling conditions

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Chinese Journal of Aeronautics 2021年第2期34卷 154-164页

作者： Ferhat kadioglu Department of Aerospace Engineering Ankara Yildirim Bcvazit University06050 UlusAnkaraTurkey

Adhesive Single Lap Joints have been subjected to tensile and bending investigations by many researchers. However, the joint is also likely to experience buckling loading in some aerospace applications. The aim of this work is to investigate the joint behaviour under quasi-static buckling conditions. For this purpose, the joints with three different adherend thicknesses and 25 mm overlap length were tested using two different types of adherends and an adhesive film. They were modelled using a non-linear Finite Element Method via the ABAQUS Explicit package *** to failure and stress distributions in the joints were predicted and compared with the experimental results, which were found in a good agreement. The adhesive layer in the joint was assumed to experience shear stresses under the buckling mode, similar to that in tensile loading, yet, the stress concentrations at the ends of the overlap, the main cause of the failure, resulted in different effects on the joint performance;for the buckling mode the critical stresses were in compression but for the tensile case in peeling. Unlike the latter, the former was found to prevent failure of the layer depending on the adherend thickness, causing different failure mechanisms. There were two different failure modes of the joints;a complete failure in the adhesive layer and large plastic deformation of adherends which could be a good source for crashworthiness situations. Mechanical properties of the adherends were found to play important roles on the joint performance.

关键词： Adhesive joins Buckling mode Energy absorption Finite element method Single lap joint

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Equivariant analytical mapping of first principles Hamiltonians to accurate and transferable materials models

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npj Computational Materials 2022年第1期8卷 1468-1481页

作者： Liwei Zhang Berk onat Geneviève Dusson Adam McSloy G.Anand Reinhard J.Maurer Christoph Ortner James R.Kermode Department of Mathematics University of British Columbia1984 Mathematics RoadVancouverBCV6T 1Z2Canada Warwick Centre for Predictive Modelling School of EngineeringUniversity of WarwickCoventryCV47ALUK Laboratoire de Mathématiques UMR CNRS 6623UniversitéBourgogne Franche-Comté16 route de Gray25030BesançonFrance Department of Metallurgy and Materials Engineering Indian Institute of Engineering Science and Technology-ShibpurHowrahWBIndia Department of Chemistry University of WarwickCoventryCV47ALUK

We propose a scheme to construct predictive models for Hamiltonian matrices in atomic orbital representation from ab initio data as a function of atomic and bond *** scheme goes beyond conventional tight binding descriptions as it represents the ab initio model to full order,rather than in two-centre or three-centre *** achieve this by introducing an extension to the atomic cluster expansion(ACE)descriptor that represents Hamiltonian matrix blocks that transform equivariantly with respect to the full rotation *** approach produces analytical linear models for the Hamiltonian and overlap *** an application to aluminium,we demonstrate that it is possible to train models from a handful of structures computed with density functional theory,and apply them to produce accurate predictions for the electronic *** model generalises well and is able to predict defects accurately from only bulk training data.

关键词： structure Hamiltonian analytical

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Prediction of Excess Air Factor in Automatic Feed Coal Burners by Processing of Flame Images

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Chinese Journal of Mechanical Engineering 2017年第3期30卷 722-731页

作者： Muhammed Fatih TALU Cem onat Mahmut DASKIN computer engineering department inonu university44280 MalatyaTurkey mechanical engineering department inonu university44280 MalatyaTurkey

In this study, the relationship between the visual information gathered from the flame images and the excess air factor 2 in coal burners is investigated. In conventional coal burners the excess air factor 2. can be obtained using very expensive air measurement instruments. The proposed method to predict ） for a specific time in the coal burners consists of three distinct and consecutive stages; a） online flame images acquisition using a CCD camera, b） extrac- tion meaningful information （flame intensity and bright- ness）from flame images, and c） learning these information （image features） with ANNs and estimate 2. Six different feature extraction methods have been used： CDF of Blue Channel, Co-Occurrence Matrix, L-Frobenius Norms, Radiant Energy Signal （RES）, PCA and Wavelet. When compared prediction results, it has seen that the use of co- occurrence matrix with ANNs has the best performance （RMSE = 0.07） in terms of accuracy. The results show that the proposed predicting system using flame images can be preferred instead of using expensive devices to measure excess air factor in during combustion.

关键词： Excess air factor Flame images Coal burner

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A novel anti-slip control approach for railway vehicles with traction based on adhesion estimation with swarm intelligence

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Railway Engineering Science 2020年第4期28卷 346-364页

作者： Abdulkadir Zirek Altan onat Department of Transport Means and Diagnostics Faculty of Transport EngineeringUniversity of PardubicePardubiceCzechia Electrical and Electronics Engineering Department Engineering FacultyEskisehir Technical UniversityIki Eylul Campus26555 EskisehirTurkey School of Engineering Stephenson BuildingNewcastle UniversityNewcastle upon Tyne NE17RUUK

Anti-slip control systems are essential for railway vehicle systems with *** order to propose an effective anti-slip control system,adhesion information between wheel and rail can be ***,direct measurement or observation of adhesion condition for a railway vehicle in operation is quite ***,a proportional–integral controller,which operates simultaneously with a recently proposed swarm intelligencebased adhesion estimation algorithm,is proposed in this *** approach provides determination of the adhesion optimum on the adhesion-slip curve so that a reference slip value for the controller can be determined according to the adhesion conditions between wheel and *** validate the methodology,a tram wheel test stand with an independently rotating wheel,which is a model of some low floor trams produced in Czechia,is *** reveal that this new approach is more effective than a conventional controller without adhesion condition estimation.

关键词： Adhesion estimation Traction control Antislip control Railway vehicles Roller-rigs Swarm intelligenc

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Ischemic stroke due to carbon monoxide intoxication: Two case reports

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World Journal of Emergency Medicine 2018年第1期9卷 73-75页

作者： Atif Bayramoglu Abdullah Osman Kocak Esra kadioglu Department of Emergency Medicine Faculty of Medicine University of Ataturk

Dear editor,Following its entrance into the human body through inhalation,carbon monoxide(CO)forms carboxyhemoglobin(COHb)by binding to hemoglobin(Hb)within the *** ischemic tissue necrosis occurs in 0.5%–1% of cases... 详细信息

关键词： Figure Two case reports DWI

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A Jacobian-Free Newton Krylov Implicit-Explicit Time Integration Method for Incompressible Flow Problems

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Communications in Computational Physics 2013年第5期13卷 1408-1431页

作者： Samet Y.kadioglu Dana A.Knoll Department of Mathematical Engineering Yildiz Technical University34210 Davutpasa-EsenlerIstanbulTurkey Fuels Modeling and Simulation Department Idaho National LaboratoryP.O.Box 1625MS 3840Idaho FallsID 83415USA Theoretical Division Los Alamos National LaboratoryP.O.Box 1663MS B-216Los AlamosNM87545USA

We have introduced a fully second order IMplicit/EXplicit(IMEX)time integration technique for solving the compressible Euler equations plus nonlinear heat conduction problems(also known as the radiation hydrodynamics problems)in kadioglu et al.,***[22,24].In this paper,we study the implications when this method is applied to the incompressible Navier-Stokes(N-S)*** IMEX method is applied to the incompressible flow equations in the following *** hyperbolic terms of the flow equations are solved explicitly exploiting the well understood explicit *** the other hand,an implicit strategy is employed for the non-hyperbolic *** explicit part is embedded in the implicit step in such a way that it is solved as part of the non-linear function evaluation within the framework of the Jacobian-Free Newton Krylov(JFNK)method[8,29,31].This is done to obtain a self-consistent implementation of the IMEX method that eliminates the potential order reduction in time accuracy due to the specific operator *** employ a simple yet quite effective fractional step projection methodology(similar to those in[11,19,21,30])as our preconditioner inside the JFNK *** present results from several test *** each test,we show second order time ***,we present a study for the algorithm performance of the JFNK solver with the new projection method based preconditioner.

关键词： Incompressible flow Navier-Stokes equations IMEX method JFNK method preconditioner

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Neurovascular bundle dissection for Nesbit procedure in congenital penile curvature patients： medial or lateral？

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Asian Journal of Andrology 2014年第3期16卷 442-445页

作者： Fatih Akbulut Tolga Akman Emre Salabas Murat Dinqer Mazhar Ortac Ates kadioglu Department of Urology Haseki Training and Research Hospital Istanbul Turkey Department of Urology Istanbul Faculty of Medicine Istanbul Turkey.

The objective of this study was to compare the outcomes of the modified Nesbit procedure using different techniques for dissecting the neurovascular bundle （NVB） to correct ventral congenital penile curvatures （CPCs）. The bundle was mobilized using the medial and lateral dissection technique in 21 （Group 1） and 13 （Group 2） patients, respectively. In the medial technique, Buck＇s fascia is opened at the dorsal side of the penis, the deep dorsal vein is removed at the most prominent site of the curvature and a diamond-shaped tunica albuginea （TA） is excised from the midline of the penis. In the lateral technique, the bundle is mobilized using a longitudinal lateral incision of the Buck＇s fascia above the urethra at the 5 and 7 o＇clock positions via a bilateral approach. The localization and degree of curvature was evaluated using the combined intracavernous injection stimulation test or from the patients＇ photographs. The mean patient age and degree of curvature were similar between groups. The mean operation time was longer for Group 2 （P= 0.01）. In Group 1, nine patients （42.8%） required one diamond excision, 10 （47.6%） required two diamond excisions and two （9.5%） required more than two excisions; in Group 2, six patients （46.2%） required two diamond excisions and seven patients （53.8%） required more than two diamond excisions （P = 0.019）. The differences in penile shortening, penile straightening and numbness of the glans penis were not statistically significant. Medial dissection of the bundle for the modified Nesbit procedure reduces the number of diamond-shaped removals of TA and thus shortens operation time in comparison with its lateral counterpart.

关键词： congenital penile curvature lateral dissection medial dissection nesbit neurovascular bundle ventral curvature

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Peyronie's disease:a silent consequence of diabetes mellitus

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Asian Journal of Andrology 2006年第1期8卷 75-79页

作者： A.Tefekli E.Kandirali B.Erol M.Tunc A. kadioglu Department of Urology Istanbul UniversityIstanbul Medical FacultyIstanbul 343 90Turkey Department of Urology Izzet Baysal Medical FacultyAbant Izzet Baysal UniversityBolu 14 280Turkey

Aim： To investigate the clinical characteristics of patients with Peyronie＇s disease （PD） and diabetes mellitus （DM）. Methods： During an 8-year period, a total of 307 men seen at our outpatient clinic were diagnosed with PD. Clinical characteristics, penile deformities and the erectile status of patients with PD and DM together （n = 102） were retrospectively analyzed and compared to patients with PD alone with no risk factors for systemic vascular diseases （n = 97）. Results：The prevalence of PD among men with DM and sexual dysfunction was 10.7 %. The mean age of diabetic patients with PD was （55.9 ± 8.9） years; in the no risk factor group it was （48.5 ± 9.0） years （P 〈 0.05）. The median duration of DM was 5 years. The majority of diabetic patients with PD （56.0 %） presented in the chronic phase （P 〈 0.05）, and they were more likely to have a severe penile deformity （〉 60°） than the no risk factor group （P 〈 0.05）. In the diabetic group, the most common presenting symptom was penile curvature （81.4%）, followed by a palpable nodule on the shaft of the penis （22.5%） and penile pain with erection （14.7%）. A total of 19.6% of patients were not aware of their penile deformities in the diabetic group. Erectile function, provided by history and in response to intracavernosal injection and a stimulation test, was significantly diminished in patients with PD and DM （P 〈 0.05）. Conclusion： DM probably exaggerates the fibrotic process in PD. Diabetic patients with PD have a higher risk of severe deformity and erectile dysfunction （ED）. PD seems to be a silent consequence of DM and should be actively sought in diabetic men. （Asian JAndrol 2006 Jan; 8： 75-79）

关键词： Peyronie's disease diabetes mellitus erectile dysfunction penile deformity fibrosis

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