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Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer

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Cancer drug Resistance 2022年第3期5卷 691-702页

作者： Amy H.Tang Richard A.Hoefer Mary L.Guye harry d.bear department of Microbiology and Molecular Cell Biology Leroy T.Canoles Jr.Cancer Research CenterEastern Virginia Medical SchoolNorfolkVA 23507USA School of Systems Biology George Mason UniversityManassasVA 20110USA Sentara Cancer Network Sentara HealthcareNorfolkVA 23507USA Sentara Surgery Specialists Surgical OncologySentara CarePlex HospitalNewport NewsVA 23606USA division of Surgical Oncology Departments of Surgery and Microbiology and ImmunologyMassey Cancer CenterVirginia Commonwealth UniversityRichmondVA 23298-0011USA

Triple-negative breast cancer(TNBC)is the most aggressive breast cancer *** disproportionately affects BRCA mutation carriers and young women,especially African American(AA)*** TNBC is a heterogeneous and molecularly unstable disease that challenges our ability to apply personalized *** the approval of immune checkpoint blockade(ICB)for TNBC,the addition of pembrolizumab to systemic chemotherapy has become standard of care(SOC)in neoadjuvant systemic therapy(NST)for high-risk early-stage *** plus chemotherapy significantly increased the pathologic complete response(pCR)and improved event-free survival in ***,clinical uncertainties remain because similarly treated TNBC partial responders with comparable tumor responses to neoadjuvant therapy often experience disparate clinical *** methods fall short in accurately predicting which high-risk patients will develop chemo-resistance and tumor ***,novel treatment strategies and innovative new research initiatives are *** propose that the EGFR-K-RAS-SIAH pathway activation is a major tumor driver in chemoresistant *** high expression of SIAH in residual tumors following NACT/NST reflects that the EGFR/K-RAS pathway remains activated(ON),indicating an ineffective response to *** chemoresistant tumor clones persist in expressing SIAH(SIAH^(High/ON))and are linked to early tumor relapse and poorer ***,the loss of SIAH expression(SIAH^(Low/OFF))in residual tumors post-NACT/NST reflects EGFR/K-RAS pathway inactivation(OFF),indicating effective therapy and chemo-sensitive tumor ***^(Low/OFF) signal is linked to tumor remission and better prognosis post-NACT/***,SIAH is well-positioned to become a novel tumor-specific,therapy-responsive,and prognostic ***,this new biomarker(SIAH^(High/ON))could be used to quantify therapy response,predict chemo-resistance,and identi

关键词： Triple-negative breast cancer(TNBC) chemo-resistance seven in absentia(SINA)and human homologs of SINA(SIAH)E3 ligase ubiquitin-mediated proteolysis EGFR/K-RAS/SIAH pathway activation in TNBC neoadjuvant chemotherapy prognosis patient risk stratification detection of chemo-resistance precision quantification of therapy efficacy and treatment optimization

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Amelioration of habitat since the early Holocene contributed to the origin of agriculture in the farming-pastoral zone of northern China

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Science China Earth Sciences 2024年第8期67卷 2535-2546页

作者： Xin JIA Zhiping ZHANG Yonggang SUN Runqi JIANG Shuangwen YI Wei CHEN Jue SUN Guoqiang LI Shuzhi WANG Enrui LI Xiaonong HU Qingchun BAO harry F.LEE Huayu LU Jiangsu Center for Collaborative Innovation in Geographical Information Resource development and Application Nanjing 210023China Schlool of History and Culture Chifeng UniversityChifeng 024000China School of Geography and Ocean Science Nanjing UniversityNanjing 210023China State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and PalaeontologyChinese Academy of SciencesNanjing 210008China Key Laboratory of Western China’s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesLanzhou UniversityLanzhou 730000China Institute of Archaeology Chinese Academy of Social SciencesBeijing 100710China Ulanqab Museum Ulanqab 012000China The Institute of Cultural Relics and Archaeology Hohhot 010011China department of Geography and Resource Management The Chinese University of Hong KongHong Kong 999077China Key Laboratory of Virtual Geographic Environment(Ministry of Education of PRC) Nanjing Normal UniversityNanjing 210023China School of Geography Nanjing Normal UniversityNanjing 210023China Institute of Environmental Archaeology Nanjing Normal UniversityNanjing 210023China

The origin of agriculture in the farming-pastoral zone of northern China remains in *** central region of the Inner Mongolia Plateau is located in the core area of the farming-pastoral zone;thus,it is a critical region for exploring the origin of the dryland farming system in northern *** study selected the Yumin Site and Banan Site,which belong to the Yumin Culture-the beginning of Neolithic culture in Inner Mongolia-as the research *** on the quartz optically stimulated luminescence(OSL)dating on the sedimentary sections from the Yumin site(YM)and Banan site(BN1 and BN2),the Holocene chronology framework of each section was *** that,by identifying carbonized grains in the Yumin site and the multi-proxy analysis of each section,we investigated the relationship between the origin of agriculture and climate change in this *** results revealed that the timing of the origin of agriculture recorded in the Yumin site lagged behind the timing of a significant increase of precipitation during the early Holocene but coincided with the timing of a significant increase of vegetation around 8.4 *** phenomenon was further confirmed by the published high-resolution paleoenvironmental records from the surrounding area of the Yumin *** propose that with the gradual amelioration of hydrothermal conditions since the beginning of the Holocene,the regional ecosystem had been improved,resulting in the gradual conversion of the land surface from infertile sand to organic-rich soil,providing an appropriate environmental foundation for the origin of dryland farming in northern China around 8.4 *** study highlighted that the“accumulative environmental effects”during the early Holocene played a vital role in the origin of agriculture in northern China and provided a reference for agricultural management in the context of future climate change.

关键词： Origin of agriculture Accumulative environmental effects Yumin Culture Northern China Holocene

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无弹性物质参与的密封是未来的趋势

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流程工业 2024年第4期 14-17页

作者： harry Jost Anja Quattelbaum Matthias dörr NEUMO GmbH+Co.KG

即将实施的PFAS(全氟和多氟烷基化合物)禁令以及更严格的TA Luft(空气清洁技术标准)排放限值,是当前困扰着化工和生命科学行业从业者的两大热门话题。这使得管道连接如何能够实现安全密封并符合法规要求成为焦点问题。本文描述了制药、... 详细信息

即将实施的PFAS(全氟和多氟烷基化合物)禁令以及更严格的TA Luft(空气清洁技术标准)排放限值,是当前困扰着化工和生命科学行业从业者的两大热门话题。这使得管道连接如何能够实现安全密封并符合法规要求成为焦点问题。本文描述了制药、生物科技、食品和化工及氢能领域在这样的政策环境下所面临的问题,并给出了解决方案。此外,本文还特别介绍了不含弹性密封材料的管道连接件,并强调了无弹性物质参与的密封是未来的趋势。

关键词：连接件密封交叉污染

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Is Robotic Arm Assisted Total Hip Arthroplasty More Bone Preserving than Conventional Hip Replacements and Hip Resurfacing?

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Open Journal of Orthopedics 2022年第6期12卷 259-267页

作者： Rajitha Gunaratne Ben Levy harry d’Souza Arash Taheri Curtin University Bentley Australia Joondalup Health Campus Joondalup Australia Sir Charles Gairdner Hospital North Metropolitan Health Service Nedlands Australia Joondalup Orthopaedic Group Joondalup Australia

Background: Total hip arthroplasty (THA) is a common procedure that is increasingly being performed in younger patients. deep acetabular reaming will result in more bone loss and the need for large acetabular components to be implanted. It can also lead to impingement, loosening, an altered center of rotation, and intraoperative periprosthetic fracture. The purpose of this study is to determine whether the single ream, robotic arm-assisted (RAA) THA can preserve a greater volume of bone stock compared to conventional hip replacement and resurfacing. Methods: We prospectively recruited 69 patients who had undergone primary THA using the Stryker Trident Acetabular System®in combination with the Stryker RAA System (MAKO)®and compared their mean reaming weight (g) with that of conventional hip replacement and resurfacing, as measured by Brennan et al. Comparison of acetabular reaming during hip resurfacing versus uncemented THA (J Orthop Surg. 2009;17(1): 42-46). Results: The mean reaming weight using the MAKO system was 9.08 g, which was 29% less than the reaming weight using uncemented THA and hip resurfacing of 12.75 g. None of the acetabular cups required screw fixation. during the 35-month follow-up period, there were no complications related to cup placement or positioning. Conclusions: The use of RAA THA results in statistically significant preservation of acetabular bone compared to conventional hip replacement and resurfacing. This approach reflects the increased precision offered by RAA single reaming. Surgeons may consider utilizing RAA THA, particularly in younger patients, to better preserve bone stock as this could potentially impact future revision procedures.

关键词： Arthroplasty Replacement Hip

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Folding metamaterials with extremely strong electromagnetic resonance

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Photonics Research 2022年第9期10卷 2215-2222页

作者： harry MIYOSI SILALAHI WEI-FAN CHIANG YI-HONG SHIH WAN-YI WEI JOU-YU SU CHIA-YI HUANG department of Applied Physics Tunghai UniversityTaichung 40704China department of Photonics Taiwan Cheng Kung UniversityTainan 70101China

Aqueous solutions cannot be detected using transmissive terahertz metamaterials because water strongly absorbs terahertz *** terahertz metamaterials are easier to integrate terahertz emitters and receivers into single and compact devices than reflective terahertz *** detection of aqueous solutions using transmissive terahertz metamaterials is a big *** work fabricates a transmissive terahertz metamaterial using a folding metamaterial comprising split-ring resonators(SRRs)with nano-profiles with a high aspect ratio *** folding metamaterial has a small transmittance of-49 d B at its resonance frequency,large transmittance contrast of approximately 6×10^(4)with respect to the transmittance of its substrate,large refractive index sensitivity of 647 GHz/RIU,and large quality factor of *** result arises from the nano-profiles of the *** nanoprofiles increase the surface areas of the SRRs,increasing their surface currents and enhancing the electromagnetic resonance of the folding *** folding metamaterial detects a 188-μm-thick rabbit-blood layer that is deposited on it,which cannot be detected by using a common *** result reveals that folding metamaterials have potential in detecting the products of live microorganisms with geometrical sizes up to several hundreds of micrometers,such as hydrogen gas,hydrocarbons,and antibodies.

关键词： resonance sizes integrate

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3d U-Net Segmentation Improves Root System Reconstruction from 3d MRI Images in Automated and Manual Virtual Reality Work Flows

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Plant Phenomics 2023年第3期5卷 598-611页

作者： Tobias Selzner Jannis Horn Magdalena Landl Andreas Pohlmeier dirk Helmrich Katrin Huber Jan Vanderborght harry Vereecken Sven Behnke Andrea Schnepf Forschungszentrum Juelich GmbH Agrosphere(IBG-3)JuelichGermany Autonomous Intelligence Systems Group University of BonnBonnGermany Forschungszentrum Juelich GmbH Juelich Supercomputing CenterJuelichGermany

Magnetic resonance imaging(MRI)is used to image root systems grown in opaque ***,reconstruction of root system architecture(RSA)from 3-dimensional(3d)MRI images is *** resolution and poor contrast-to-noise ratios(CNRs)hinder automated ***,manual reconstruction is still widely ***,we evaluate a novel 2-step work flow for automated RSA *** the first step,a 3d U-Net segments MRI images into root and soil in *** the second step,an automated tracing algorithm reconstructs the root systems from the segmented *** evaluated the merits of both steps for an MRI dataset of 8 lupine root systems,by comparing the automated reconstructions to manual reconstructions of unaltered and segmented MRI images derived with a novel virtual reality *** found that the U-Net segmentation offers profound benefits in manual reconstruction:reconstruction speed was doubled(+97%)for images with low CNR and increased by 27%for images with high *** root lengths were increased by 20%and 3%,***,we propose to use U-Net segmentation as a principal image preprocessing step in manual work *** root length derived by the tracing algorithm was lower than in both manual reconstruction methods,but segmentation allowed automated processing of otherwise not readily usable MRI ***,model-based functional root traits revealed similar hydraulic behavior of automated and manual *** studies will aim to establish a hybrid work flow that utilizes automated reconstructions as scaffolds that can be manually corrected.

关键词： Root utilize otherwise

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Formation of carbon and oxygen rich surface layer on high purity magnesium by atmospheric carbon dioxide plasma

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Journal of Magnesium and Alloys 2023年第1期11卷 88-99页

作者： Gyoung G.Jang Sinchul Yeom Jong K.Keum Mina Yoon harry III Meyer Yi-Feng Su Jiheon Jun Manufacturing Science division Oak Ridge National Laboratory(ORNL)One Bethel Valley RoadPO Box 2008MS6054Oak RidgeTN 37831United States Material Science and Technologies division Oak Ridge National Laboratory(ORNL)One Bethel Valley RoadOak RidgeTN 37831United States Neutron Scattering division&Center for Nanophase Materials Sciences ORNLOne Bethel Valley RoadOak RidgeTN 37831United States Chemical Sciences division ORNLOne Bethel Valley RoadOak RidgeTN 37831United States

Carbon and oxygen-rich corrosion barrier layer formed on Mg by a simple and scalable CO_(2) atmospheric plasma(CO_(2)-AP)*** reactive CO_(2)-AP interacts with the Mg surface and forms a unique layered structure with the top MgCO_(3)/MgO-intermixed particulates pillars and the bottom dense *** surface features were simultaneously formed on the nano-/micro-structured MgO layer by carbonate molecules,plasma-active CO_(2) molecules,and/or other volatile organic compounds on the nano-/micro-structured MgO particle *** resulting surfaces after CO_(2)-AP were either hydrophobic or hydrophilic and exhibited lower anodic current or high resistance for Mg *** the hydrophobic surfaces of CO_(2)-AP treated Mg,molecular dynamic simulations were performed to understand the origin of hydrophobicity and identified that the amorphous carbon layers formed on the Mg surface are the *** environmentally benign abundant-gas-based process enables the cost reduction associated with waste treatment,generation of by-product,and supply of raw material.

关键词： Atmospheric plasma Magnesium Corrosion protection Surface modification

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Sperm speed is associated with sex bias of siblings in a human population

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Asian Journal of Andrology 2013年第1期15卷 152-154页

作者： Jim A Mossman Jon Slate Tim R Birkhead harry d Moore Allan A Pacey department of Ecology and Evolutionary Biology Box G Brown University Providence Rhode Island 02912 USA department of Animal and Plant Sciences University of Sheffield Western Bank Sheffield S10 2TN UK Centre for Stem Cell Biology Department of Biomedical Sciences University of Sheffield Western Bank Sheffield $10 2TN UK Academic Unit of Reproductive and developmental Medicine Department of Human Metabolism School of Medicine and Biomedical Sciences Sheffield $10 2SF UK

Recent studies investigating possible causes of male subfertility have largely focused on how lifestyle or environmental factors impact on the process of spermatogenesis, Markedly, fewer studies have investigated those risk factors that result in reduced sperm quality, such as poor sperm motility. The speed at which sperm swim is a major predictor of fertility and is extremely variable in human populations. It has been hypothesized that offspring sex may be adaptively manipulated to maximize the offspring＇s reproductive fitness （e.g., parents with genes for good male fertility traits, such as high sperm speed, would produce primarily sons and fewer daughters because the offspring will inherit advantageous male fertility genes）. Conversely, parents with poor male fertility genes would produce primarily daughters, We tested whether there was an association between how fast a man＇s sperm swam and the sex bias of his siblings in a sample of men attending clinic for fertility investigations with their partner and with a wide range of semen characteristics, including sperm speed. We found that the sex bias of a man＇s siblings is associated with his sperm speed; men with female-biased siblings had significantly slower sperm （judged using computer-assisted sperm analysis （CASA）） than men from male-biased sibships. This observation suggests family composition is an important factor that needs to be considered in future edidemiological and clinical studies of human fertility,

关键词： computer-assisted sperm analysis (CASA) fertility intralocus sexual conflict male offspring sex ratio sexual antagonism

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Highly efficient GaAs solar cells by limiting light emission angle

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Light(Science & Applications) 2013年第1期2卷 236-241页

作者： Emily d Kosten Jackson H Atwater James Parsons Albert Polman harry A Atwater Thomas J.Watson Laboratories of Applied Physics California Institute of TechnologyPasadenaCA 91125 USA Center for Nanophotonics FOM-Institute AMOLFScience Park 1041098XG AmsterdamThe Netherlands

In a conventional flat plate solar cell under direct sunlight,light is received from the solar disk,but is re-emitted *** isotropic emission corresponds to a significant entropy increase in the solar cell,with a corresponding drop in ***,using a detailed balance model,we show that limiting the emission angle of a high-quality GaAs solar cell is a feasible route to achieving power conversion efficiencies above 38%with a single *** highest efficiencies are predicted for a thin,light trapping cell with an ideal back reflector,though the scheme is robust to a non-ideal back *** with a conventional planar cell geometry illustrates that limiting emission angle in a light trapping geometry not only allows for much thinner cells,but also for significantly higher overall efficiencies with an excellent rear ***,we present ray-tracing and detailed balance analysis of two angular coupler designs,show that significant efficiency improvements are possible with these couplers,and demonstrate initial fabrication of one coupler design.

关键词： detailed balance GaAs solar cell light trapping photovoltaics two photon lithography

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Quantitative analysis of the impact of droughts and floods on internal wars in China over the last 500 years

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Science China Earth Sciences 2017年第12期60卷 2078-2088页

作者： harry F.LEE david d.ZHANG PEI Qing JIA Xin Ricci P.H.YUE department of Geography and International Center for China development Studies The University of Hong Kong School of Geographical Sciences Guangzhou University department of Social Sciences The Education University of Hong Kong School of Geographic and Oceanographic Sciences Nanjing University

Although many large-N quantitative studies have evidenced the adverse effects of climatic extremes on social stability in China during the historical period, most of them rely on temperature and precipitation as major explanatory variables, while the influence of floods and droughts on social crises is rarely measured. Furthermore, a comparison of the climate-society nexus among different geographic regions and at different temporal scales is missing in those studies. To address this knowledge gap,this study examines quantitatively the influence of floods and droughts on internal wars in three agro-ecological(rice, wheat,and pastoral) regions in China in Ad1470–1911. Poisson regression and wavelet transform coherence analyses are applied to allow for the non-linear and non-stationary nature of the climate-war nexus. Results show that floods and droughts are significant in driving internal wars in historical China, but are characterized by strong regional variation. In the rice region, floods trigger internal wars at the inter-annual and multi-decadal time scales. In the wheat region, both floods and droughts cause internal wars at the inter-annual and multi-decadal time scales. In the pastoral region, internal wars are associated with floods only at the multi-decadal time scale. In addition, the multi-decadal coherence between hydro-climatic extremes and internal wars in all three of the agro-ecological regions is only significant in periods in which population density is increasing or the upper limit of regional carrying capacity is being reached. The above results imply that the climate-war nexus is mediated by regional geographic factors such as physical environmental setting and population pressure. Hence, we encourage researchers who study the historical human-climate relationship to boil down data according to geographic regions in the course of statistical analysis and to examine each region individually in follow-up studies.

关键词： Floods and droughts Climatic extremes Internal wars Wars Social stability Ming-Qing period

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