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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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3DPMD-Arc-based additive manufacturing with titanium powder as raw material

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China Welding 2019年第1期28卷 11-15页

作者： hoefer Kevin Mayr Peter Chemnitz University of Technology

The study aims to demonstrate the suitability of the 3DPMD for the production of titanium components with and without reinforcing particles in layer-by-layer design. Various demonstrators are prepared and analyzed. The microstructure, the porosity and the hardness values of the different structures are compared with each other through metallographic cross-sections. The uniform distribution of the carbides and the interaction with the matrix was analyzed by SEM and *** miller-test method(ASTM G75-07) was used to determine data for the relative abrasivity of the structures. In summary, 3DPMD offers the possibility to produce titanium structures with and without reinforced particles. Using automated routines, it is possible to generate metal structures using welding robots directly from the CAD drawings. Microstructures and properties are directly related to the process and therefore material-process-property relationships are discussed within this work.

关键词： additive manufacturing plasma titanium 3D plasma metal deposition reinforced particles

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A Fast Test System to Evaluate the Physical Protection Potential of Textiles against Blood-Sucking Insects

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Journal of Textile Science and Technology 2018年第3期4卷 79-84页

作者： Timo Hammer Anja Gerhardts Dirk hoefer Hohenstein Institute Boennigheim Germany

Blood-sucking insects can cause severe health damage in humans and animals for example by causing allergic reactions or by the propagation of vector-borne diseases such as malaria. Textiles are widely used for insect protection with bednets, curtains or outdoor clothing. The main approach is functionalization of the textiles with insect repellents like DEET or insecticides like permethrin. Instead of or in addition to these chemical measures the mechanical protection potential of the fabric itself has to be considered for preventing insect bites and stings effectively. Densely woven fabrics or spacer fabrics can serve as a chemical-free protection system. To compare the physical protection potential of different textiles against the mouthparts and stings of blood-sucking insects, we developed an easy and reliable test system which can be used in textile research institutes and companies. The system is mobile and can also be applied on wet textiles. We here describe the construction and validation of our new test system.

关键词： Malaria Mouthpart Outdoor Spacer Fabric Vector-Protection

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通过KMS转炉和二次精炼生产连铸高质量钢

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钢铁译文集 1992年第2期 1-5页

作者： hoefer,F

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通过KMS转炉和二次精炼生产连铸优质钢

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国外钢铁 1991年第3期16卷 18-22页

作者： hoefer,F 李大公

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搭载人类自体干细胞的纤维支架及其在软组织再生中的应用

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纺织导报 2018年第5期 52-54页

作者： Marina Handel Timo Hammer Dirk hoefer 德国海恩斯坦研究院

文章介绍了搭载人类自体干细胞的纤维支架技术及其在软组织再生中的应用优势。选用藻酸盐材料结合人体干细胞搭载关键技术制成的纤维支架,同时具有促进血管再生和触发成脂分化的能力。

关键词：藻酸盐支架自体干细胞软组织再生

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Impact of conditioning regimen on peripheral blood hematopoietic cell transplant

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World Journal of Clinical Oncology 2019年第2期10卷 86-97页

作者： Michael Burns Anurag K Singh Carrie C hoefer Yali Zhang Paul K Wallace George L Chen Alexis Platek Timothy B Winslow Austin J Iovoli Christopher Choi Maureen Ross Philip L McCarthy Theresa Hahn Department of Medicine Roswell Park Comprehensive Cancer Center Department of Radiation Medicine Roswell Park Comprehensive Cancer Center Department of Flow Cytometry Roswell Park Comprehensive Cancer Center Center for Immunotherapy Roswell Park Comprehensive Cancer Center

AIM To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/-total body irradiation(TBI) on outcomes after peripheral blood hematopoietic cell transplant(PBHCT).METHODS Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank *** Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning(RIC) + TBI] and > 4 × 10~6 CD34+cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group(P = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless ofconditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 ×10~8/kg(3 years, overall survival: 70% vs 38%, P = 0.02, 3 years, progression free survival: 64% vs 38%, P = 0.02).CONCLUSION TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.

关键词： Total body radiation Peripheral blood hematopoietic cell transplant Total nucleated dose Neutrophil engraftment Graft-versus-host-disease

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鳍线设计的经验表达式

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系统工程与电子技术 1986年第2期 62-65页

作者： A.K.Sharma ,W.J.R.hoefer ,刘锡阳 ,黄文鑫

本文提出一组适于封闭电路形式的单面鳍线和双面鳍线设计的经验公式。用这些经验公式计算的波导波长和特性阻抗值与用频谱法在归一化频率范围为0.35≤b/λ≤0.70时测得值一致,差值在±2％以内。

关键词：鳍线表达式归一化截止频率等效介电常数

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新泽特博物馆和文献中心，新泽特，德国

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世界建筑 2008年第4期 70-75页

作者：温德尔.霍夫尔.洛施+赫施建筑师事务所徐知兰 Till Whler

新泽特村周围的景观属于典型的德国田园风光，有平缓的小山和农庄田野。建筑地段上没有留下丝毫痕迹．能使人联想起在1939年-1945年之间，这里曾经是关押着20多国政治犯的集中营。由温德尔·霍夫尔·洛施＋赫施建筑师事务所完成的获奖... 详细信息

新泽特村周围的景观属于典型的德国田园风光，有平缓的小山和农庄田野。建筑地段上没有留下丝毫痕迹．能使人联想起在1939年-1945年之间，这里曾经是关押着20多国政治犯的集中营。由温德尔·霍夫尔·洛施＋赫施建筑师事务所完成的获奖设计，对这一地段在政治意义和地理区域上的畸变提出了质疑：

关键词：德国博物馆建筑师事务所文献田园风光地理区域地段政治

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健康幼儿循环炎症趋化因子和血管特性的关系

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中华高血压杂志 2015年第11期23卷 1005-1005页

作者：刘莉叶鹏 Eikendal AL Evelein AM Uiterwaal CS van der Ent CK Visseren FL Bots ML hoefer IE den Ruijter HM Dalmeijer GW

动脉粥样硬化始于儿童时期,并伴随血管壁炎性变化,可用B型超声检测出,趋化因子参与这些变化它们作为血管炎症介质,出现在动脉粥样硬化的早期然而该现象并没有被广泛研究。因此,该文研究人员探讨健康幼儿的趋化因子单核细胞趋化蛋白1（mo... 详细信息

动脉粥样硬化始于儿童时期,并伴随血管壁炎性变化,可用B型超声检测出,趋化因子参与这些变化它们作为血管炎症介质,出现在动脉粥样硬化的早期然而该现象并没有被广泛研究。因此,该文研究人员探讨健康幼儿的趋化因子单核细胞趋化蛋白1（mono cyte chemotactic protein 1,MCP-1）、

关键词：趋化因子炎性变化炎症介质超声检测细胞间黏附分子 intercellular 颈总动脉 RANTES secreted 喘息性疾病

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