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Clinical implications of the molecular characterization of intraductal papillary mucinous neoplasms of the pancreas

Journal of Cancer Metastasis and Treatment 2021年第1期7卷 430-447页

作者： nicholas v.peters John W.Kunstman Department of Surgery Yale University School of MedicineNew Haven 06510CTUSA.

Intraductal papillary mucinous neoplasm(IPMN)is a pre-malignant,mucin-producing epithelial lesion arising from pancreatic *** reports define IPMN behavior as ranging from indolent,asymptomatic lesions to dysplasia that sometimes degenerate into pancreatic *** goal of IPMN management is risk-reducing surgery for high-risk cysts and observation of the *** high-from low-risk IPMN disease still relies on imaging and clinical cyst ***,we review the accepted classification of IPMN including the most common histological subtypes,their clinical features,and currently-accepted high-risk *** then deeply examine the known molecular landscape of IPMN,which has largely been derived from post-resection *** includes those gene variants unique to IPMN,chiefly GNAS and RNF43,but also examines the overlap between IPMN and conventional pancreatic *** molecular markers in the clinical setting relies on endoscopically-obtained cyst fluid and presumes that it accurately represents the molecular characteristics of the cystic *** synthesize existing data on mutational analysis from IPMN cyst fluid and consider the benefits and proper role of current commercially-available cyst fluid molecular analysis *** conclude that carefully interpreted molecular analysis of resected IPMN tissue reveals insights into its biology and natural history while cyst fluid analysis offers prognostication and data to guide treatment ***,knowledge gaps remain,especially in characterizing IPMN molecular heterogeneity,time to progression,and correlating cyst fluid genotype data with surveillance *** such,substantial additional research is required before the promise of true molecular guidance of IPMN management can be realized.

关键词： Intraductal papillary mucinous neoplasm pancreatic cancer molecular analysis GNAS KRAS RNF43

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Design and synthesis of synthetic promoters for consistency of gene expression across growth phases and scale in ***

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Synthetic and Systems Biotechnology 2024年第2期9卷 330-339页

作者： Kristin v.Presnell Omar Melhem Sarah M.Coleman nicholas J.Morse Hal S.Alper McKetta Department of Chemical Engineering The University of Texas at Austin200E Dean Keeton St.Stop C0400AustinTX78712USA Institute for Cellular and Molecular Biology The University of Texas at Austin2500 Speedway AvenueAustinTX78712USA

Metabolic engineering and synthetic biology endeavors benefit from promoters that perform consistently(or robustly)with respect to cellular growth phase(exponential and stationary)and fermentation scale(microtiter plates,tubes,flasks,and bioreactors).However,nearly all endogenous promoters(especially in Saccharomyces cerevisiae)do not perform in this *** this work,a hybrid promoter engineering strategy is leveraged to create novel synthetic promoters with robustness across these *** a multi-dimensional RNA-seq dataset,promoters with specific phase dependencies were *** enriched with functional transcription factors were identified using MEME *** motif-containing fragments could impart activity dependence in the opposing ***,we obtain two new promoters with high and consistent expression across both phases by increasing the exponential phase activity of the starting stationary-phase scaffold by 38 and 23-fold ***,we show that these promoters function consistently across various laboratory growth scales over time in a microtiter plate and in ***,this work presents and validates a new strategy for engineering promoters in *** with high levels of expression that are robust to cellular growth phase and the scale of the culture.

关键词： endogenous synthetic stationary

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Aggregation-induced emission polymers via reversible-deactivation radical polymerization Special Collection:Distinguished Australian Researchers

Aggregate

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Aggregate 2024年第1期5卷 16-46页

作者： nicholas Kai Shiang Teo Bo Fan Aditya Ardana San H.Thang School of Chemistry Monash UniversityClaytonVictoriaAustralia

Aggregation-induced emission(AIE)is a unique phenomenon whereby aggregation of molecules induces fluorescence emission as opposed to the more commonly known aggregation-caused quenching(ACQ).AIE has the potential to be utilized in the large-scale production of AIE-active polymeric materials because of their wide range of practical applications such as stimuli-responsive sensors,biological imaging agents,and drug delivery *** is evident from the increasing number of publications over the years since AIE was first *** addition,the evergrowing interest in this field has led many researchers around the world to develop new and creative methods in the design of monomers,initiators and crosslinkers,with the goal of broadening the scope and utility of AIE *** of the most promising approaches to the design and synthesis of AIE polymers is the use of the reversible-deactivation radical polymerization(RDRP)techniques,which enabled the production of well-controlled AIE materials that are often difficult to achieve by other *** this review,a summary of some recent works that utilize RDRP for AIE polymer design and synthesis is presented,including(i)the design of AIE-related monomers,initiators/crosslinkers;the achievements in preparation of AIE polymers using(ii)reversible addition–fragmentation chain transfer(RAFT)technique;(iii)atom transfer radical polymerization(ATRP)technique;(iv)other techniques such as Cu(0)-RDRP technique and nitroxide-mediated polymerization(NMP)technique;(v)the possible applications of these AIE polymers,and finally(vi)a summary/perspective and the future direction of AIE polymers.

关键词： aggregation-induced emission atom transfer radical polymerization nitroxide-mediated polymerization reversible addition–fragmentation chain transfer reversible-deactivation radical polymerization

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Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 52-61页

作者： Silvia Ribback Kristin peters Mohd Yasser Jessica Prey Paula Wilhelmi Qin Su Frank Dombrowski Peter Bannasch Institut für Pathologie Universitaetsmedizin GreifswaldGreifswaldGermany Cell Marque Millipore-SigmaRocklinCAUSA German Cancer Research Center(DKFZ) HeidelbergGermany

Background and Aims:Hepatocellular ballooning is a common finding in chronic liver disease,mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies(MDB).Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes(BH)are damaged cells on the path to death or rather viable cells,possibly involved in neoplastic ***:Using specimens from 96 cirrhotic human livers,BH characteristics were assessed for their glycogen/lipid stores,enzyme activities,and proto-oncogenic signaling cascades by enzyme-and immunohistochemical approaches with serial paraffin and cryostat ***:BH were present in 43.8%of cirrhotic *** pronounced excess glycogen storage of(glycogenosis)and/or lipids(steatosis)were characteristic,ground glass features and MDB were often *** glucose-6-phosphatase,increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis,lipid metabolism,and cholesterol biosynthesis were ***,components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo ***:BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis,many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver ***,BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming,indicative of a preneoplastic nature.

关键词： Chronic liver disease Carbohydrate metabolism Insulin signaling Preneoplasia Metabolic reprogramming

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Recent advances in intermediate-temperature CO_(2) capture: Materials,technologies and applications

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Journal of Energy Chemistry 2024年第3期90卷 435-452,I0010页

作者： Chengbo Zhao Leiming Wang Liang Huang nicholas M.Musyoka Tianshan Xue Jabor Rabeah Qiang Wang Engineering Research Center for Water Pollution Source Control&Eco-remediation College of Environmental Science and EngineeringBeijing Forestry UniversityBeijing 100083China State Key Laboratory of Efficient Production of Forest Resources Beijing Forestry UniversityBeijing 100083China China Machinery Huanyu Certification and Inspection Co. Ltd.Beijing 102609China Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute University of Nottingham Ningbo ChinaNingbo 315100ZhejiangChina Institute of Atmospheric Environment Chinese Research Academy of Environmental SciencesBeijing 100012China Leibniz-Institut für Katalyse e.v. Albert-Einstein-Str.29aRostock D-18059Germany

Carbon capture,utilization and storage(CCUS) is widely recognized as a vital strategy for mitigating the impact of human induced climate *** various CO_(2) adsorbents,intermediate-temperature solid adsorbents have garnered significant attention due to their potential applications in hydrogen utilization,specifically in the water gas shift,steam reforming and gasification *** processes are crucial for achieving carbon *** laboratory-level studies have showcased the high adsorption capacity of these materials via various synthesis and modification methods,their practical application in complex industrial environments remains challenging,impeding the commercialization *** review aims to critically summarize the recent research progress made in intermediatetemperature(200-400℃) solid CO_(2) adsorbents,particularly focusing on indicators such as cyclability,gas selectivity,and formability,which play vital roles in industrial application ***,we provide an overview of laboratory-level advanced technologies specifically tailored for industrial ***,we highlight several industrial-ready advanced technologies that can pave the way for overcoming the challenges associated with large-scale *** insights provided by this review aim to assist researchers in identifying the most relevant research directions for industrial *** promoting advances in the application of solid adsorbents,we strive to facilitate the ultimate goal of achieving carbon neutrality.

关键词： Intermediate-temperature CO_(2) capture MgO LDHs Industrialization

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HDPairFinder:A data processing platform for hydrogen/deuterium isotopic labeling-based nontargeted analysis of trace-level amino-containing chemicals in environmental water

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Journal of Environmental Sciences 2024年第2期136卷 583-593页

作者： Tingting Zhao Kristin Carroll Caley B.Craven nicholas J.P.Wawryk Shipei Xing Jian Guo Xing-Fang Li Tao Huan Department of Chemistry Faculty of ScienceUniversity of British ColumbiaVancouver Campus2036 Main MallVancouverBritish ColumbiaV6T 1Z1Canada Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

The combination of hydrogen/deuterium(H/D)formaldehyde-based isotopic methyl labeling with solid-phase extraction and high-performance liquid chromatography–high resolution mass spectrometry(HPLC-HRMS)is a powerful analytical solution for nontargeted analysis of trace-level amino-containing chemicals in water *** the huge amount of chemical information generated in HPLC-HRMS analysis,identifying all possible H/Dlabeled amino chemicals presents a significant challenge in data *** address this,we designed a streamlined data processing pipeline that can automatically extract H/D-labeled amino chemicals from the raw HPLC-HRMS data with high accuracy and ***,we developed a cross-correlation algorithm to correct the retention time shift resulting from deuterium isotopic effects,which enables reliable pairing of H-and D-labeled ***,we implemented several bioinformatic solutions to remove false chemical features generated by in-source fragmentation,salt adduction,and natural13C ***,we used a data mining strategy to construct the AMINES library that consists of over 38,000 structure-disjointed primary and secondary amines to facilitate putative compound ***,we integrated these modules into a freely available R program,*** rationale of each module was justified and its performance tested using experimental H/D-labeled chemical standards and authentic water *** further demonstrated the application of HDPairFinder to effectively extract N-containing contaminants,thus enabling the monitoring of changes of primary and secondary N-compounds in authentic water *** is a reliable bioinformatic tool for rapid processing of H/D isotopic methyl labeling-based nontargeted analysis of water samples,and will facilitate a better understanding of N-containing chemical compounds in water.

关键词： Isotope labeling Nontargeted analysis Reactive N-compounds HPLC-HRMS Source water

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Modeling West Nile virus transmission in birds and humans:Advantages of using a cellular automata approach

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Infectious Disease Modelling 2024年第1期9卷 278-297页

作者： Baki Cissé David R.Lapen KChalvet-Monfray nicholas H.Ogden Antoinette Ludwig Public Health Sciences Division National Microbiology LaboratoryPublic Health Agency of CanadaSt-HyacintheCanada Groupe de Recherche enÉpidémiologie des Zoonoses et SantéPublique(GREZOSP) Facultéde Médecine VétérinaireUniversitéde MontréalSaint-HyacintheQuébecCanada Ottawa Research and Development Centre Science and Technology BranchAgriculture and Agri-Food CanadaOttawaK1A 0C6Canada Universitéde Lyon INRAEVetAgro SupUMR EPIAMarcy l’EtoileFrance UniversitéClermont Auvergne INRAEVetAgro SupUMR EPIASaint-Genès-ChampanelleFrance

In Canada,the periodic circulation of West Nile virus(WNv)is difficult to predict and,beyond climatic factors,appears to be related to the migratory movements of infected birds from the southern United *** hypothesis has not yet been explored in a spatially distributed *** main objective of this work was to develop a spatially explicit dynamic model for the transmission of WNv in Canada,that allows us to explore non-climate related hypotheses associated with WNv transmission.A Cellular Automata(CA)approach for multiple hosts(birds and humans)is used for a test region in eastern Ontario,*** tool is designed to explore the role of host and vector spatial heterogeneity,host migration,and vector feeding *** developed a spatialized compartmental SEIRDS-SEI model for WNv transmission with a study region divided into 4 rectangular *** used 2010–2021 bird data from the eBird project and 2010–2019 mosquito data collected by Ontario Public Health to mimic bird and mosquito seasonal *** considered heterogeneous bird densities(high and low suitability areas)and homogeneous mosquito and human *** high suitability areas for birds,we identified 5 entry points for WNv-infected *** compared our simulations with pools of WNv-infected field collected *** and sensitivity analyses were performed using MATLAB *** results showed good correspondence between simulated and observed epidemics,supporting the validity of our model assumptions and *** analysis showed that a 5%increase or decrease in each parameter of our model except for the biting rate of bird by mosquito(c^(B,M)and mosquito natural mortality rate(d^(M)),had a very limited effect on the total number of cases(newly infected birds and humans),prevalence peak,or date of *** demonstrate the utility of the CA approach for studying WNv transmission in a heterogeneous landscape with multiple hosts.

关键词： Cellular automata Mosquito-borne diseases SEIRDS-SEI modeling West Nile virus

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Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults

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Sports Medicine and Health Science 2024年第1期6卷 54-62页

作者： Rian Q.Landers-Ramos Kathleen Dondero Ian Imery nicholas Reveille Hannah A.Zabriskie Devon A.Dobrosielski Towson University Department of KinesiologyTowsonMDUSA University of Maryland School of Medicine Department of Physical Therapy and Rehabilitation SciencesBaltimoreMDUSA Johns Hopkins University Department of Cell BiologyBaltimoreMDUSA University of Florida Department of Applied Physiology and KinesiologyGainesvilleFLUSA

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy *** study aimed to compare flow mediated dilation(FMD)and vascular augmentation index(AIx75)between young adults with low,moderate,and high levels of cardiorespiratory fitness before and after an acute bout of aerobic ***-three participants(22 men;21 women)between 18 and 29 years of age completed the *** were classified into low,moderate,and high health-related cardiorespiratory fitness groups according to age-and sex-based relative maximal oxygen consumption(v_O2 max)percentile *** was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70%v_O2 max.A significant interaction(p=0.047;ηp 2=0.142)was observed,with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline([6.7%3.1%]vs.[8.5%2.8%],p=0.028;d=0.598).We found a significant main effect of group for AIx75(p=0.023;ηp 2=0.168),with the high fitness group exhibiting lower AIx75 compared to low fitness group([10%10%]vs.[2%10%],respectively,p=0.019;g=1.07).This was eliminated after covarying for body fat percentage(p=0.489).Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness,but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

关键词： Cardiorespiratory fitness Flow mediated dilation Augmentation index vascular Acute exercise Body composition

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Surface hydrolysis-mediated PEGylation of poly(N-isopropyl acrylamide)based nanogels

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Regenerative Biomaterials 2017年第5期4卷 281-287页

作者： Jonathan T.peters Stanley verghese Deepak Subramanian nicholas A.Peppas McKetta Department of Chemical Engineering The University of Texas at AustinAustinTXUSA Institute for Biomaterials Drug Deliveryand Regenerative MedicineThe University of Texas at AustinAustinTXUSA Department of Biomedical Engineering The University of Texas at AustinAustinTXUSA Department of Pediatrics and Department of Surgery and Perioperative CareDell Medical SchoolThe University of Texas at AustinAustinTXUSA Division of Pharmaceutics College of PharmacyThe University of Texas at AustinAustinTXUSA

In this work,poly(N-isopropyl acrylamide-co-acrylamide)[P(NIPAAm-co-AAm)]nanogels were modified by hydrolysis above the lower critical solution temperature(LCST)to localize carboxylic acid functional groups at the surface(surface hydrolysis).PNIPAAm copolymerized with 15%and 20%nominal AAm in the feed were prepared and compared to equivalent hydrogels with acrylic *** effect and extent of surface hydrolysis was confirmed by potentiometric titration and zeta *** surface modified nanogels were then modified with primary amine functionalized PEG *** hydrolysis-mediated PEGylation had little effect on the swelling response of the nanogels,while also preventing adsorption of model proteins in physiological relevant *** both 15%and 20%AAm gels both decreased protein adsorption,only the 20%AAm gels resulted in fully preventing protein *** results presented here point to surface hydrolysis as a new route to passivate nanogels for use in vivo.

关键词： PNIPMAAm hydrogels PEG passivation

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Animal personalities and their implications for complex signaling

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Current Zoology 2014年第3期60卷 381-386页

作者： nicholas DIRIENZO Ann v HEDRICK Department of Neurobiology Physiology & Behavior Animal Behavior Graduate Group University of California Davis CA 95616 USA Department of Neurobiology Physiology & Behavior University of California Davis CA 95616 USA

Animal personalities have been a major focus of behavioral ecology over the past decade. Consistent individual dif ferences in behavior have been found across taxa, and have been shown to influence a range of ecological processes. The role of personalities in sexual selection has been considered, and examples exist that show selection for personality traits with both assortative and disassortative mating patterns between personality types. One overlooked aspect of the personality and sexual se lection literature is the potential for personalitysignaling interactions, specifically with complex signaling. Complex signaling is a diverse topic in itself, and in short, consists of multiple signals within one or more modalities that interact to elicit a receiver response. Research into complex signaling has been thorough, although at times studies discover complex signaling systems that fail to fit into one of the existing hypotheses in the literature. Here, we argue that personalities may interact with complex signal ing, which should be considered by researchers of both personality and sexual selection and communication. We describe several ways in which personalitycomplex signaling interactions could affect both the signaler and receiver, and the way in which they may drive personalityspecific signals as well as receiver preferences. Finally, we discuss how considering personality in com plex signaling studies may inform theory as well as improve the ability of researchers to accurately describe its function.

关键词： Animal Personalities Sexual Selection Complex Signaling Multimodal Communication Communication

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