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Genomic stability at the coding regions of the multidrug transporter gene ABCB1: insights into the development of alternative drug resistance mechanisms in human leukemia cells

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Cancer Drug Resistance 2020年第4期3卷 959-979页

作者： Kevin G.Chen George E.Duran mark j.mogul Yan C.Wang Kevin L.Ross jean-Pierre jaffrézou Lyn M.Huff Kory R.johnson Tito Fojo Norman j.Lacayo Branimir I.Sikic Division of Oncology Department of MedicineStanford University School of MedicineStanfordCA 94305USA Current Address:NIH Stem Cell Unit National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA Current Address:Medical Affairs U.S. Servier PharmaceuticalsBostonMA 02210USA Current Address:Ross BioPharm Group Rocky PointNY 11778USA Current Address:French National Centre for Scientific Research Paris 75016France Medicine Branch National Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Current Address Laboratory of Cell BiologyNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Intramural IT and Bioinformatics Program National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA Current Address:Herbert Irving Comprehensive Cancer Center Columbia University Medical Center/New York-Presbyterian HospitalNew YorkNY 10032USA Division of Pediatric Hematology-Oncology-Stem Cell Transplantation and Cancer Biology Stanford University School of Medicine and Stanford Cancer InstitutePalo AltoCA 94305USA

Aim:Despite considerable efforts to reverse clinical multidrug resistance(MDR),targeting the predominant multidrug transporter ABCB1/P-glycoprotein(P-gp)using small molecule inhibitors has been unsuccessful,possibly due to the emergence of alternative drug resistance ***,the non-specific P-gp inhibitor cyclosporine(CsA)showed significant clinical benefits in patients with acute myeloid leukemia(AML),which likely represents the only proof-of-principle clinical trial using several generations of MDR ***,the mutational mechanisms that may underlie unsuccessful MDR modulation by CsA are not elucidated because of the absence of CsA-relevant cellular *** this study,our aims were to establish CsA-resistant leukemia models and to examine the presence or absence of ABCB1 exonic mutations in these models as well as in diverse types of human cancer samples including ***:Drug-resistant lines were established by stepwise drug co-selection and characterized by drug sensitivity assay,rhodamine-123 accumulation,[3H]-labeled drug export,ABCB1 cDNA sequencing,and RNase protection *** genomic stability of the ABCB1 coding regions was evaluated by exome sequencing analysis of variant allele frequencies in human ***,the mutational spectrum of ABCB1 was further assessed in diverse types of cancer samples including AMLs in the Cancer Genome Atlas(TCGA)at the National Cancer ***:We report the development of two erythroleukemia variants,RVC and RDC,which were derived by stepwise co-selection of K562/R7 drug-resistant leukemia cells with the etoposide-CsA and doxorubicin-CsA drug combinations,***,both RVC and RDC cell lines,which retained P-gp expression,showed altered multidrug-resistant phenotypes that were resistant to CsA ***,no mutations were found in the ABCB1 coding regions in these variant cells even under long-term stringent drug ***,ABCB1

关键词： Cancer leukemia multidrug resistance ABCB1 P-glycoprotein cyclosporine mutation

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Analysis of the inflection points of height-diameter models

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Forest Ecosystems 2024年第4期11卷 414-422页

作者： Tzeng Yih Lam mark j.Ducey Department of Forest Resources Management Faculty of ForestryThe University of British Columbia2045-2424 Main MallVancouverBCV6T 1Z4 Canada Department of Natural Resources and the Environment University of New Hampshire114 James HallDurhamNH 03824USA

The inflection point is an important feature of sigmoidal height-diameter(H-D)*** is often cited as one of the properties favoring sigmoidal model ***,there are very few studies analyzing the inflection points of H-D *** goals of this study were to theoretically and empirically examine the behaviors of inflection points of six common H-D models with a regional *** six models were the Wykoff(WYK),Schumacher(SCH),Curtis(CUR),HossfeldⅣ(HOS),von Bertalanffy-Richards(VBR),and Gompertz(GPZ)*** models were first fitted in their base forms with tree species as random effects and were then expanded to include functional traits and spatial *** distributions of the estimated inflection points were similar between the two-parameter models WYK,SCH,and CUR,but were different between the threeparameter models HOS,VBR,and *** produced some of the largest inflection *** and VBR produced concave H-D curves without inflection points for 12.7%and 39.7%of the tree *** species or decreasing shade tolerance resulted in larger inflection *** trends in the estimated inflection points of HOS and VBR were entirely opposite across the ***,HOS could produce concave H-D curves for portions of the *** on the studied behaviors,the choice between two-parameter models may not *** recommend comparing seve ral three-parameter model forms for consistency in estimated inflection points before deciding on *** sigmoidal models to have inflection points does not necessarily mean that they will produce fitted curves with *** study highlights the need to integrate analysis of inflection points into modeling H-D relationships.

关键词： Concavity Forest inventory and analysis Generalized height-diameter models Growth functions Height-diameter functions Mixed-effects modeling Points of inflection Species-specific models

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What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang john A.Kershaw mark j.Ducey Yuan Sun james B.McCarter Integrated Forest Mensuration and Systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China Scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New Brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships Stand structure Volume estimation Stand-level attributes

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Management of monogenic diabetes in pregnancy:A narrative review

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World journal of Diabetes 2024年第1期15卷 15-23页

作者： Mohammad Sadiq jeeyavudeen Sarah R Murray mark W j Strachan Metabolic Unit Western General HospitalEdinburgh EH42XUUnited Kingdom MRC Centre for Reproductive Health University of Edinburgh Queen’s Medical Research InstituteEdinburgh EH164TJUnited Kingdom

Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal *** these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical *** subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant *** MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes *** glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing *** pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available *** of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case ***,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.

关键词： Diabetes Pregnancy Maturity-onset diabetes of the young Insulin Sulphonylurea Glucokinase Hepatocyte nuclear factor 1-alpha,hepatocyte nuclear factor 1-beta,and hepatocyte nuclear factor 4-alpha

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Olympic Games and 24-hour movement behaviors:A match worth making

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journal of Sport and Health Science 2024年第6期13卷 728-731页

作者： mark S.Tremblay Nicholas Kuzik markus j.Duncan Diego Augusto Santos Silva CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina FlorianopolisSanta Catarina 88040-900Brazil

*** The Olympic motto,"Faster,Higher,Stronger-Together",represents the pursuit of athletic excellence,united as a global community."Excellence,respect and friendship"are the Olympic *** the motto and values are multifaceted and holistic in nature,and all-encompassing in their reach while recognizing no single entity rises above the ***,these foundational statements anchor the Olympic movement in its quest to build a better world through sport.

关键词： movement Together pursuit

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Towards precision 24-hour movement behavior recommendations—The next new paradigm?

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journal of Sport and Health Science 2024年第6期13卷 743-748页

作者： mark S.Tremblay markus j.Duncan Nicholas Kuzik Diego Augusto Santos Silva Valerie Carson CHEO Research Institute OttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada Federal University of Santa Catarina Santa Catarina 88040900Brazil Faculty of Kinesiology Sportand RecreationUniversity of AlbertaEdmontonAB T6G 2H9Canada

*** The importance of physical activity(PA)for health is unequivocal.^(1)Accordingly,population-based recommendations for exercise,and more recently public health guidelines for PA,have been developed and released by authoritative groups for many decades.^(2)Such guidelines emerged with leadership from the exercise physiology discipline and were rooted in,and loyal to,the importance of moderate-to-vigorous intensity PA(MVPA)or exercise.

关键词： movement behavior exercise

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Anneal-free ultra-low loss silicon nitride integrated photonics

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Light(Science & Applications) 2024年第8期13卷 1565-1577页

作者： Debapam Bose mark W.Harrington Andrei Isichenko Kaikai Liu jiawei Wang Nitesh Chauhan Zachary L.Newman Daniel j.Blumenthal Department of Electrical and Computer Engineering University of California Santa BarbaraSanta BarbaraCA 93106USA Octave Photonics LouisvilleCO 80027USA

Heterogeneous and monolithic integration of the versatile low-loss silicon nitride platform with low-temperature materials such as silicon electronics and photonics,III–V compound semiconductors,lithium niobate,organics,and glasses has been inhibited by the need for high-temperature annealing as well as the need for different process flows for thin and thick *** techniques are needed to maintain the state-of-the-art losses,nonlinear properties,and CMOS-compatible processes while enabling this next generation of 3D silicon nitride *** report a significant advance in silicon nitride integrated photonics,demonstrating the lowest losses to date for an anneal-free process at a maximum temperature 250℃,with the same deuterated silane based fabrication flow,for nitride and oxide,for an order of magnitude range in nitride thickness without requiring stress mitigation or *** report record low anneal-free losses for both nitride core and oxide cladding,enabling 1.77 dBm-1 loss and 14.9 million Q for 80 nm nitride core waveguides,more than half an order magnitude lower loss than previously reported sub 300℃ *** 800 nm-thick nitride,we achieve as good as 8.66 dBm-1 loss and 4.03 million Q,the highest reported Q for a low temperature processed resonator with equivalent device area,with a median of loss and Q of 13.9 dBm-1 and 2.59 million each *** demonstrate laser stabilization with over 4 orders of magnitude frequency noise reduction using a thin nitride reference cavity,and using a thick nitride micro-resonator we demonstrate OPO,over two octave supercontinuum generation,and four-wave mixing and parametric gain with the lowest reported optical parametric oscillation threshold per unit resonator *** results represent a significant step towards a uniform ultra-low loss silicon nitride homogeneous and heterogeneous platform for both thin and thick waveguides capable of linear and nonlinear photonic circuits and integrat

关键词： resonator thick free

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Extremely thin but very robust:Surprising cryptogam trait combinations at the end of the leaf economics spectrum

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Plant Diversity 2024年第5期46卷 621-629页

作者： Tana Wuyun Lu Zhang Tiina Tosens Bin Liu Kristiina mark joséÁngel Morales-Sanchez jesamine jöneva Rikisahedew Vivian Kuusk Ülo Niinemets Institute of Agricultural and Environmental Sciences Estonian University of Life SciencesKreutzwaldi 1Tartu 51014Estonia College of Landscape and Architecture Zhejiang A&F University666 Wusu StreetHangzhou 311300China Estonian Academy of Sciences Kohtu 6Tallinn 10130Estonia

Leaf economics spectrum(LES)describes the fundamental trade-offs between leaf structural,chemical,and physiological ***,structurally robust thick leaves with high leaf dry mass per unit area(LMA)exhibit lower photosynthetic capacity per dry mass(Amass).Paradoxically,“soft and thinleaved”mosses and spikemosses have very low Amass,but due to minute-size foliage elements,their LMA and its components,leaf thickness(LT)and density(LD),have not been systematically ***,we characterized LES and associated traits in cryptogams in unprecedented details,covering five evolutionarily different *** found that mosses and spikemosses had the lowest LMA and LT values ever measured for terrestrial *** a broad range of species from different lineages,Amass and LD were negatively *** contrast,Amass was only related to LMA when LMA was greater than 14 g cm^(-2).In fact,low Amass reflected high LD and cell wall thickness in the studied *** conclude that evolutionarily old plant lineages attained poorly differentiated,ultrathin mesophyll by increasing *** plant lineages,LD,not LMA,is the trait that represents the trade-off between leaf robustness and physiology in the LES.

关键词： Investment strategy Leaf density Leaf structural traits LMA estimation bias Non-seed plants Trait trade-offs

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A Simulation of the Dependence of Tidal Interaction on Galaxy Type in Compact Groups

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International journal of Astronomy and Astrophysics 2024年第2期14卷 85-100页

作者： mark j. Henriksen Mateo Mejia Department of Physics University of Maryland Baltimore USA

We have investigated the role that different galaxy types have in galaxy-galaxy interactions in compact groups. N-body simulations of 6 galaxies consisting of a differing mixture of galaxy types were run to compare the relative importance of galaxy population demographic on evolution. Three different groups with differing galaxy content were tested: all spiral, a single elliptical and 50% elliptical. Tidal interaction strength and duration were recorded to assess the importance of an interaction. A group with an equal number of spiral and elliptical galaxies has some of the longest and strongest interactions with elliptical-elliptical interactions being most significant. These elliptical-elliptical interactions are not dominated by a single large event but consist of multiple interactions. Elliptical galaxies tidally interacting with spiral galaxies, have the next strongest interaction events. For the case when a group only has a single elliptical, the largest magnitude tidal interaction is an elliptical on a spiral. Spirals interact with each other through many small interactions. For a spiral only group, the interactions are the weakest compared to the other group types. These spiral interactions are not dominated by any singular event that might be expected to lead to a merger but are more of an ongoing harassment. These results suggest that within a compact group, early type galaxies will not form via merger out of an assemblage of spiral galaxies but rather that compact groups, in effect form around an early type galaxy.

关键词： Galaxy Groups Galaxy Clusters Galaxy Evolution N-Body Simulations

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A novel diagnostic gene region for distinguishing between two pest fruit flies:Bactrocera tryoni(Froggatt)and Bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa L.Starkie Elizabeth V.Fowler Alexander M.Piper Xiaocheng Zhu Pauline Wyatt David Gopurenko Matt N.Krosch Francesca Strutt Karen F.Armstrong Hamish Patrick mark K.Schutze mark j.Blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of Primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of Pest-management and Conservation Lincoln UniversityLincolnNew Zealand Better Border Biosecurity(B3 B3nz.org.nz)LincolnNew Zealand

Bactrocera tryoni and Bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adjacent single nucleotide polymorphisms(SNPs)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)PCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adjacent SNPs(AA)present in *** and the other targeting adjacent SNPs present in ***(GG).The assay accurately discriminates between the two species,but their SNP genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-PCR colony molecular diagnostics pangolin tetra-primer

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