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Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

Signal Transduction and Targeted Therapy 2018年第1期3卷 237-245页

作者： nicholas lsyn Pei Li Lim Li Ren Kong Lingzhi Wang Andrea Li-Ann Wong Chwee Ming Lim Thomas Kwok Seng Loh Gerhard Siemeister Boon Cher Goh Wen-Son Hsieh Cancer Science Institute of Singapore National University of SingaporeSingaporeSingapore Department of Haematology-Oncology National University Cancer InstituteSingaporeSingapore Department of Pharmacology Yong Loo Lin School of MedicineNational University Health SystemSingaporeSingapore Department of Otolaryngology-Head and Neck Surgery National University Health SystemSingaporeSingapore Drug Discovery TRG OncologyBayer Pharma AGBerlinGermany

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human ***,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)*** of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/*** anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic *** enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug *** roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)*** administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the *** summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.

关键词： cisplatin nasopharyngeal doses

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Minimally invasive liver resection for huge(≥10cm)tumors:an international multicenter matched cohort study with regression discontinuity analyses

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 587-597,I0001-I0003页

作者： Tan-To Cheung Xiaoying Wang Mikhail Efanov Rong Liu David Fuks Gi-Hong Choi nicholas lsyn Charing CChong Iswanto Sucandy Adrian KHChiow Marco VMarino Mikel Gastaca Jae Hoon Lee TPeter Kingham Mathieu D’Hondt Sung Hoon Choi Robert PSutcliffe Ho-Seong Han Chung Ngai Tang Johann Pratschke Roberto ITroisi Brian KPGoh International Robotic and Laparoscopic Liver Resection Study Group Collaborators Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Hepato-Pancreato-Biliary Surgery Moscow Clinical Scientific CenterMoscowRussia Faculty of Hepatopancreatobiliary Surgery The First Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijingChina Department of Digestive Oncologic and Metabolic SurgeryInstitute Mutualiste MontsourisUniversite Paris DescartesParisFrance Division of Hepatopancreatobiliary Surgery Department of SurgerySeverance HospitalYonsei University College of MedicineSeoulKorea Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital and Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongNew TerritoriesHong KongChina AdventHealth Tampa Digestive Health InstituteTampaFLUSA Hepatopancreatobiliary Unit Department of SurgeryChangi General HospitalSingaporeSingapore General Surgery Department Azienda Ospedaliera Ospedali Riuniti Villa Sofia-CervelloPalermoItaly Oncologic Surgery Department P.Giaccone University HospitalPalermoItaly Hepatobiliary Surgery and Liver Transplantation Unit Biocruces Bizkaia Health Research InstituteCruces University HospitalUniversity of the Basque CountryBilbaoSpain Department of Surgery Division of Hepato-Biliary and Pancreatic SurgeryAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Surgery Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Department of Digestive and Hepatobiliary/Pancreatic Surgery Groeninge HospitalKortrijkBelgium Department of General Surgery CHA Bundang Medical CenterCHA University School of MedicineSeongnamKorea Department of Hepatopancreatobiliary and Liver Transplant Surgery University Ho

Background:The application and feasibility of minimally invasive liver resection(MILR)for huge liver tumours(≥10 cm)has not been well ***:Retrospective analysis of data on 6,617 patients who had MILR for liver tumours were gathered from 21 international centers between *** tumors and large tumors were defined as tumors with a size≥10.0 cm and 3.0-9.9 cm based on histology,respectively.1:1 coarsened exact-matching(CEM)and 1:2 Mahalanobis distance-matching(MDM)was performed according to clinically-selected *** discontinuity analyses were performed as an additional line of sensitivity analysis to estimate local treatment effects at the 10-cm tumor size ***:Of 2,890 patients with tumours≥3 cm,there were 205 huge *** 1:1 CEM,174 huge tumors were matched to 174 large tumors;and after 1:2 MDM,190 huge tumours were matched to 380 large *** was significantly and consistently increased intraoperative blood loss,frequency in the application of Pringle maneuver,major morbidity and postoperative stay in the huge tumour group compared to the large tumour group after both 1:1 CEM and 1:2 *** findings were reinforced in RD *** blood transfusion rate and open conversion rate were significantly higher in the huge tumor group after only 1:2 MDM but not 1:1 ***:MILR for huge tumours can be safely performed in expert centers It is an operation with substantial complexity and high technical requirement,with worse perioperative outcomes compared to MILR for large tumors,therefore judicious patient selection is pivotal.

关键词： Minimally invasive liver resection(MILR) robotic-assisted liver resection huge tumours hepatocellular carcinoma laparoscopic liver resection

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PROJECT MANAGEMENT:RECENT DEVELOPMENTS AND RESEARCH OPPORTUNITIES

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Journal of Systems Science and Systems Engineering 2012年第2期21卷 129-143页

作者： nicholas G.HALL Department of Management Sciences Fisher College of Business The Ohio State UniversityUSA

This paper studies the business process known as project management. This process has exhibited a remarkable growth in business interest over the last 15 years, as demonstrated by a 1000% increase in membership in the Project Management Institute since 1996. This growth is largely attributable to the emergence of many new diverse business applications that can be successfully managed as projects. The new applications for project management include IT implementations, research and development, new product and service development, corporate change management, and software development. The characteristics of modem projects are typically very different from those of traditional projects such as construction and engineering, which necessitates the development of new project management techniques. We discuss these recent practical developments. The history of project management methodology is reviewed, from CPM and PERT to the influential modem directions of critical chain project management and agile methods. We identify one important application area for future methodological change as new product and service development. A list of specific research topics within project management is discussed. The conclusions suggest the existence of significant research opportunities within project management.

关键词： Project management overview recent practical developments opportunities for research

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The formation of massif anorthosite:Petrology in reverse

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Geoscience Frontiers 2013年第2期4卷 195-198页

作者： nicholas Arndt ISTerre Universite Joseph Fourier:UMR5275CNRS1381 rue de la Piscine38400 St Martin d'HeresFrance

Massif anorthosites form when basaltic magma differentiates in crustal magma chambers to form lowdensity plagioclase and a residual liquid whose density was greater than that of enclosing crustal rocks. The plagioclase and minor pyroxene crystallized in-situ on the floor of the magma chamber to produce the anorthosite complex,and the residual liquid migrated downwards,eventually to solidify as dense Fe-rich cumulates some of which were removed to the *** movements were facilitated by high temperatures in Proterozoic continental crust,thus explaining the restriction of large anorthosite massifs to this period in Earth history.

关键词： Anorthosite Petrology Proterozoic

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Composites with high omnidirectional fracture toughness due to helical interlocking fasteners are found in gingko seed shells

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National Science Review 2023年第5期10卷 106-108页

作者： nicholas A.Kotov Department of Chemical Engineering Biointerfaces InstituteDepartment of Materials Science and EngineeringUniversity of Michigan Department of Aeronautics Imperial College London

Engineering of composites mimicking load-bearing materials from living organisms is essential for sustainable economic development and successful resolution of current and future bottle-necks of chemical,automotive,av...

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Longitudinal bicyclist,driver,and pedestrian perceptions of autonomous vehicle communication strategies

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Journal of Traffic and Transportation Engineering(English Edition) 2023年第1期10卷 31-44页

作者： nicholas N.Ferenchak Department of Civil Construction&Environmental EngineeringUniversity of New MexicoAlbuquerqueNM 87131USA

We sought to better understand how autonomous vehicle(AV)communication strategies impact human road users’*** specifically,we explored the impact of different external human-machine interface(eHMI)designs on task load,comfort,trust,and *** accomplish this,we created virtual reality(VR)scenarios where human participants interacted with AVs in biking,driving,and pedestrian *** were brought back after initial testing to explore acclimation and learning *** designs included a text-based grille eHMI,a text-based roof eHMI,a text-based driver-side door eHMI,anon-textual LED windshield strip eHMI,and a non-textual side mirror arrow *** presence of an eHMI was the strongest positive predictor of comfort,trust,and acceptance outcomes in the statistical models when controlling for all other *** was a clear divide between text-based eHMIs and non-text eHMIs with text-based eHMIs experiencing better perception *** LED Windshield experienced the worst perception *** were perception acclimation effects detected which were most notable for task load(which decreased over time)and comfort(which increased over time).Perception scores for the different eHMI designs tended to cluster over ***,the acclimation effects had less of an impact than the presence of an *** outcomes had weaker relationships with participant characteristics than with AV *** suggest that eHMI presence and design,AV behavior,and acclimation are most impactful in terms of perceptions.

关键词： Vehicle automation Communication Human-automation interaction Technology acceptance Virtual reality

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Nonlinear Model of Mean Free Surface of Waves

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China Ocean Engineering 1999年第2期14卷 155-162页

作者： nicholas DODD Ph. D. Coastal Group HR Wallingford Howbery Park Wallingford

A nonlinear model of mean free surface of waves or wave set-up is presented. The model is based on that of Roelvink (1993), but the numerical techniques used in the solution are based on the Weighted-Average Flux (WAF) method (Watson el al., 1992), with Time-Operator-Splitting (TOS) used for the treatment of the source terms. This method allows a small number of computational points to be used, and is particularly efficient in modeling wave set-up. The short wave (or primary wave) energy equation is solved by use of a more traditional Lax-Wendroff technique. A nonlinear wave theory (James, 1974) is introduced. The model described in this paper is found to be satisfactory in most respects when compared with the measurements conducted by Stive (1983) except in modeling the mean free surface very close to the mean shoreline.

关键词： mean free surface radiation stress hyperbolic wave theory nonlinear model wave propagation

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Do neuronal microvascular activation and resultant dysfunction in rheumatoid arthritis contribute to chronic pain?

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Neural Regeneration Research 2019年第1期14卷 79-81页

作者： nicholas Beazley-Long Arthritis Research UK Pain Centre & School of Life Sciences Medical School University of Nottingham

Microvascular dysfunction and rheumatoid arthritis(RA):Across the UK severe osteoarthritis affects～5–7%and RA affects～1%of the *** are the most common causes of disabling chronic pain and are major burdens on individuals and ***,the annual financial cost to the UK economy for arthritis is in the billions of *** living with painful inflammatory conditions and

关键词：风湿性关节炎机能障碍疼痛激活骨关节炎心血管糖尿病 RA

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Analytical model for predicting folding stable state of bistable deployable composite boom

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Chinese Journal of Aeronautics 2024年第8期37卷 460-469页

作者： Tianwei LIU Jiangbo BAI nicholas FANTUZZI School of Transportation Science and Engineering Beihang UniversityBeijing 100191China Jingdezhen Research Institute of Beihang University Jingdezhen 333000China DICAM Department University of BolognaBologna 40136Italy

Bistable Deployable Composite Boom(Bi-DCB)can achieve bistable function by storing and releasing strain energy,which has a good application prospect in space *** example,it serves as the main support section of deployable structures(e.g.,solar arrays and antennas).This paper investigates folding stable state of Bi-DCB through the analytical *** on Archimedes’helix and energy principle,an analytical model for predicting folding stable state of Bi-DCB was *** failure index of Bi-DCB in folding stable state were analyzed using the Tsai-Hill criterion and the maximum stress ***,a 2400 mm long Bi-DCB was fabricated using autoclave *** prediction results of the proposed model were compared with experiments and results of two other analytical *** is shown that the proposed model shows good prediction ***,the effect of geometric parameters on folding stable state of Bi-DCB was further investigated with the aid of the proposed model.

关键词： Bistable Deployable composite boom Solar arrays Antennas Archimedes’helix Folding Failure analysis

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Is speciation driven by cycles of mixing and isolation?

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National Science Review 2019年第2期6卷 291-292页

作者： nicholas H.Barton Institute of Science and Technology Austria NSR

He et al.[1] describe genetic divergence between mangrove species that are distributed across the Straits of Malacca. Divergence varies much more across the genome than in a simple null model of strict allopatry. Such heterogeneity (often termed ‘genomic islands of speciation’) can be generated by population structure:populations that exchange genes at a low rate will

关键词： Rev

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