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Acta Geologica Sinica(English Edition) 2016年第S1期90卷 84-85页

作者： Wilson TEIXEIRA mike a.hamilton Vicente A.V.GIRARDI Frederico M.FALEIROS University of Sao Paulo Institute of Geosciences Jack Satterly Geochronology Laboratory Department of Earth SciencesUniversity of Toronto

High-resolution U–Pb(ID-TIMS,baddeleyite)ages are presented for mafic dykes from selected swarms in two important Amazonian regions:the Carajás Province in the east,and the Rio Apa block in the southwest–areas

关键词： Pb U-Pb Constraints on Supercontinent Cycles and Geodynamic Connections with Global LIP Events Through Time Key Dolerite Dyke Swarms of Amazonia LIP

Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： SANDRA STICKLER BARBARA RATH GERHARD hamilton Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma virus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractive target for ***,the most common KRAS mutations in PDAC are G12D(44%),G12V(34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor(GEF)Son of Sevenless 1 that drives *** agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

Development of PROTACS degrading KRAS and SOS1

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Oncology Research 2024年第8期32卷 1257-1264页

作者： GERHARD hamilton MARIE-THERESE EGGERSTORFER SANDRA STICKLER Institute of Pharmacology Medical University of ViennaVienna1090Austria

The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung ***,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of ***,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 *** approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of ***,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal *** of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not *** CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental *** to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin *** highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

关键词： Proteolysis-targeting chimeras(PROTACs) Kirsten rat sarcoma virus(KRAS) Son of sevenless 1(SOS1) Von Hippel-Lindau Cereblon

How Agent Orange impacts prostate cancer risk,pathology,and treatment outcomes

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Current Urology 2024年第2期18卷 79-86页

作者： Awais Paracha Zohair Siddiqui Ali Abid Ekamjit Deol Fatima Waheed Zachary hamilton Saint Louis University School of Medicine Saint LouisMOUSA Saint Louis University Saint LouisMOUSA New York Institute of Technology College of Osteopathic Medicine OldWestburyNYUSA Department of Surgery Division of UrologySaint Louis University School of MedicineSaint LouisMOUSA

Between 2.6 and 3.8 million veterans served in Vietnam while the US military dispersed Agent Orange(AO),although the exact number of exposed individuals is *** Orange,an herbicide,is a known risk factor for various cancers,including sarcoma and leukemia,but less is known about its link with prostate cancer(PC).Prostate cancer is the most commonly diagnosed malignancy in men and the fifth most common cause of cancer-related death in men *** 2023,approximately 288,300 patients will be given a diagnosis of PC,and an estimated 34,700 fatalities will occur in the United ***,whether the pathologic characteristics of PC among those exposed to AO differ from those in the general population remains *** review synthesizes the literature regarding the impact of AO exposure on PC incidence and disease course.A comprehensive PubMed literature search of articles published beginning in 1950 was performed using the primary search terms“Agent Orange,”“TCDD,”and“tetrachlorodibenzodioxin”and the secondary search terms“prostate cancer”or“prostate neoplasm.”The search was limited to studies that focused on human participants and were published in *** authors thoroughly reviewed the retrieved articles for relevancy to the study aims:discussion of PC diagnosis,prognosis,or management among patients exposed to *** 108 studies identified in our search,13 were included in this systematic *** within studies concerning AO exposure with relation to PC incidence,age at diagnosis or treatment initiation,and PC severity seemed to be mixed and generally ***,the literature seems to indicate that there are no significant differences in survivorship between exposed and unexposed veterans who are given a diagnosis of *** these heterogeneous outcomes,the evidence does not encourage a significantly different approach to the diagnosis and management of PC for veterans exposed to *** shouldmake case-by-case decision

关键词： Agent Orange 2,3,7,8-Tetrachlorodibenzo-p-dioxin Prostate cancer Veterans

Ballistic response of armour plates using Generative Adversarial Networks

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Defence Technology（防务技术） 2022年第9期18卷 1513-1522页

作者： S.Thompson F.Teixeira-Dias M.Paulino a.hamilton Institute for Infrastructure and Environment(IIE) School of EngineeringThe University of Edinburgh Alexander Graham Bell BuildingThe King's BuildingsEdinburghEH93FGUnited Kingdom School of Engineering Faculty of ScienceEngineering and Built EnvironmentDeakin University Waurn PondsVictoria3220Australia Data Science and AI EngineeringGroup Chief Information O CeLloyds Banking Group69 Morrison StEdinburghEH38BWUnited Kingdom

It is important to understand how ballistic materials respond to impact from projectiles such that informed decisions can be made in the design process of protective armour systems. Ballistic testing is a standards-based process where materials are tested to determine whether they meet protection, safety and performance criteria. For the V50ballistic test, projectiles are fired at different velocities to determine a key design parameter known as the ballistic limit velocity(BLV), the velocity above which projectiles perforate the target. These tests, however, are destructive by nature and as such there can be considerable associated costs, especially when studying complex armour materials and systems. This study proposes a unique solution to the problem using a recent class of machine learning system known as the Generative Adversarial Network(GAN). The GAN can be used to generate new ballistic samples as opposed to performing additional destructive experiments. A GAN network architecture is tested and trained on three different ballistic data sets, and their performance is compared. The trained networks were able to successfully produce ballistic curves with an overall RMSE of between 10 and 20 % and predicted the V50BLV in each case with an error of less than 5 %. The results demonstrate that it is possible to train generative networks on a limited number of ballistic samples and use the trained network to generate many new samples representative of the data that it was trained on. The paper spotlights the benefits that generative networks can bring to ballistic applications and provides an alternative to expensive testing during the early stages of the design process.

关键词： Machine learning Generative Adversarial Networks GAN Terminal ballistics Armour systems

Spatial analysis of the osteoarthritis microenvironment: techniques, insights, and applications

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Bone Research 2024年第1期12卷 1-19页

作者： Xiwei Fan Antonia Rujia Sun Reuben S.E.Young Isaac O.Afara Brett R.hamilton Louis Jun Ye Ong Ross Crawford Indira Prasadam Centre for Biomedical Technologies Queensland University of TechnologyBrisbaneQLDAustralia School of Mechanical Medical&Process EngineeringQueensland University of TechnologyBrisbaneQLDAustralia Central Analytical Research Facility Queensland University of TechnologyBrisbaneQLDAustralia Molecular Horizons University of WollongongWollongongNSWAustralia Department of Technical Physics University of Eastern FinlandKuopioFinland School of Electrical Engineering and Computer Science Faculty of EngineeringArchitecture and Information TechnologyUniversity of QueenslandBrisbaneQLDAustralia Centre for Microscopy and Microanalysis University of QueenslandBrisbaneQLDAustralia The Prince Charles Hospital BrisbaneQLDAustralia

Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose *** presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial ***,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic *** analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint *** issue has led to standardization difficulties and hindered the success of clinical *** insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease *** resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular *** advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial *** fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial ***,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and *** these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease *** review summarizes the rec

关键词： insight Spatial enable

Colorful facial markings are associated with foraging rates and affiliative relationships in a wild group-living cichlid fish

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Current Zoology 2024年第1期70卷 70-78页

作者： Brett M.Culbert James B.Barnett Isaac Y.Ligocki Matthew G.Salena Marian Y.L.Wong Ian M.hamilton Sigal Balshine Department of Integrative Biology University of GuelphGuelphOntarioCanada Department of Psychology Neuroscience&BehaviourMcMaster UniversityHamiltonOntarioCanada Department of Evolution Ecologyand Organismal BiologyThe Ohio State UniversityColumbusOHUSA Department of Biology Millersville UniversityMillersvillePAUSA School of Earth Atmospheric and Life SciencesUniversity of WollongongWollongongNew South WalesAustralia Department of Mathematics The Ohio State UniversityColumbusOHUSA

Many animals use color to signal their quality and/or behavioral *** signals have been well studied in the contexts of competi-tion and mate choice;however,the role of these signals in nonsexual,affiliative relationships is not as well ***,we used wild social groups of the cichlid fish Neolamprologus pulcher to investigate whether the size of a brightly colored facial patch was related to 1)individual quality,2)social dominance,and/or 3)affiliative *** with larger patches spent more time foraging and tended to perform more aggressive acts against conspecific territory *** did not find any evidence that the size of these yellow patches was related to social rank or body size,but dominant males tended to have larger patches than dominant ***,patch size had a rank-specific relationship with the number of affiliative interactions that individuals engaged *** males with large patches received fewer affiliative acts from their groupmates compared to dominant males with small ***,subordinates with large patches tended to receive more affiliative acts from their groupmates while performing fewer affiliative acts *** together,our results suggest that patch size reflects interindividual variation in foraging effort in this cichlid fish and offer some of the first evidence that colorful signals may shape affiliative relationships withinwildsocialgroups.

关键词： affiliation foraging Lake Tanganyika Neolamprologus pulcher visual signals

A Historical Perspective on Development of Systems Engineering Discipline:A Review and Analysis

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Journal of Systems Science and Systems Engineering 2020年第1期29卷 1-35页

作者： Niamat Ullah Ibne Hossain Raed M.Jaradat Michael a.hamilton Charles B.Keating Simon R.Goerger Department of Industrial and Systems Engineering Mississippi State UniversityPO Box 9542Mississippi State 39762USA Department of Industrial and Systems Engineering Mississippi State UniversityPO Box 9542Mississippi State39762USA Institute for Systems Engineering Research(ISER) Mississippi State University 3909 Halls Ferry RdVicksburgMS 39180 Department of Engineering Management&Systems Engineering Old Dominion UniversityNorfolkVA 23529 eInstitute for Systems Engineering Research(ISER) U.S Army Engineer Research Development Center(ERDC)3909 Halls Ferry RdVicksburgMS 39180

Since its inception,Systems Engineering(SE)has developed as a distinctive discipline,and there has been significant progress in this field in the past two *** to other engineering disciplines,SE is not affirmed by a set of underlying fundamental propositions,instead it has emerged as a set of best practices to deal with intricacies stemming from the stochastic nature of engineering complex systems and addressing their *** the existing methodologies and paradigms(dominant patterns of thought and concepts)of SE are very diverse and somewhat *** appears to create some confusion regarding the design,deployment,operation,and application of *** purpose of this paper is 1)to delineate the development of SE from 1926-2017 based on insights derived from a histogram analysis,2)to discuss the different paradigms and school of thoughts related to SE,3)to derive a set of fundamental attributes of SE using advanced coding techniques and analysis,and 4)to present a newly developed instrument that could assess the performance of systems *** than Two hundred and fifty different sources have been reviewed in this research in order to demonstrate the development trajectory of the SE discipline based on the frequency of publication.

关键词： Systems Engineering(SE) history development systems engineering attributes performance measures

New U-Pb Ages for Mafic Dykes of SE Greenland

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Acta Geologica Sinica(English Edition) 2016年第S1期90卷 81-82页

作者： Mimmi K.M.NILSSON Michael a.hamilton Department of Geology Lund University Department of Earth Sciences University of Toronto

The North Atlantic Craton(NAC)represents one of approximately three dozen preserved Archean cratonic fragments now dispersed globally,but its affinity to formerly neighboring supercontinent cratonic blocks

关键词： Pb New U-Pb Ages for Mafic Dykes of SE Greenland SE

Leptomeningeal metastases in prostate cancer:A review of the current literature

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Current Urology 2024年第3期18卷 159-166页

作者： Umar Durrani Kasem Rifai Maha Arshad Awais Paracha Ekamjit Deol Maria Paracha Fatima Waheed Zohair Siddiqui Ali Abid Esed Mustafic Wilson Rodriguez Zachary hamilton Saint Louis University School of Medicine Saint LouisMOUSA University of Missouri School of Medicine ColumbiaMOUSA University of Virginia CharlottesvilleVAUSA New York Institute of Technology College of Osteopathic Medicine Old WestburyNYUSA Saint Louis University Saint LouisMOUSA Department of Neurology Saint Louis University School of MedicineSaint LouisMOUSA Division of Urology Department of SurgerySaint Louis University School of MedicineSaint LouisMOUSA

Leptomeningeal metastasis/leptomeningeal carcinomatosis(LMC;terms used interchangeably)is an inflammatory complication of primary tumors that involves the spread of the disease to the meninges(specifically the arachnoid and pia maters)and spinal *** the United States,approximately 110,000 new cases are diagnosed each year,and the prognosis is usually *** of LMC include cognitive impairment,cranial nerve dysfunction,ischemic stroke,and *** survival times of untreated and treated LMC are approximately 4–6 weeks and 2–4 months,*** carcinomatoses are usually metastatic cancers that spread to the central nervous *** lung and breast cancers have a clearly defined relationship with LMC,it remains unclear whether prostate cancer(PC)is also directly associated with *** determine whether such association exists,we conducted a PubMed review of the literature on patients with PC with coexisting *** search yielded 23 case reports of patients with preexisting PC who developed *** addition,2 retrospective cohort studies were *** findings were identified in the revised cases and *** first 3 findings were related to the progression of the disease:patients presenting with neurological disease symptoms were in remission from PC for 7 years on average,LMCs tended to occur after other cancer diagnoses,and the disease had already rapidly progressed by the time the symptoms were *** diagnosis,the major finding was that most LMCs were detected by magnetic resonance imaging(which does not detect early dissemination),and it was suggested that single-photon emission computed tomography or positron emission tomography imaging could be used for earlier ***,in terms of treatment,the main finding was that treatment was palliative rather than curative and that prognosis remained poor despite *** the basis of these results,we recommend for individuals with risk facto

关键词： Leptomeningeal carcinomatosis Prostate cancer Prostate cancer metastasis