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Advanced oropharyngeal squamous cell carcinoma: pathogenesis, treatment, and novel therapeutic approaches

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world Journal of Clinical Oncology 2016年第1期7卷 15-26页

作者： paul L Swiecicki Kelly M Malloy Francis p worden Division of Hematology/Oncology Department of Internal Medicine University of Michigan Comprehensive Cancer Center Department of Otolaryngology University of Michigan Health System University of Michigan Comprehensive Cancer Center

Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus(HpV) and present with locally advanced tumors. HpV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HpV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. we also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.

关键词： Oropharyngeal cancer Human papilloma virus Transoral robotic surgery Immunotherapy Metastatic head and neck squamous cell carcinoma

STEp卫星加速度计测量头线圈的超导特性测试及改进

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光学精密工程 2010年第11期18卷 2421-2429页

作者：杨勇曹喜滨王肃文 D.GILL R.TORRII J.MESTER p.worden 哈尔滨工业大学卫星技术研究所黑龙江哈尔滨150080 斯坦福大学汉森实验室美国加州943054085

为确保STEp卫星超高精度加速度计的测量头线圈三维超导膜在设计的工作电流范围内完全超导,以实现10-18g精度的加速度测量,对测量头线圈进行了低温超导测试,测试证明三维超导膜存在不完全超导缺陷。利用分段测试法对三维膜线圈的二维组... 详细信息

为确保STEp卫星超高精度加速度计的测量头线圈三维超导膜在设计的工作电流范围内完全超导,以实现10-18g精度的加速度测量,对测量头线圈进行了低温超导测试,测试证明三维超导膜存在不完全超导缺陷。利用分段测试法对三维膜线圈的二维组成部分进行了测试,确定了测量头线圈超导缺陷的位置,并分析了造成超导缺陷的原因。根据测试和分析结果改进了线圈设计,实现了测量头线圈的完全超导,并标定线圈的最大工作电流为-40～40mA,满足STEp卫星加速度计对超导电流要求的-10～10mA,设计裕度达到300%。通过测试、分析与改进设计,定型了STEp卫星超高精度加速度计测量头线圈的研制,为完成STEp任务奠定了技术基础。同时,实现了三维超导膜线圈的制造与工程应用。

关键词：加速度计超导量子干涉仪测量头线圈三维超导膜低温超导等效原理检验卫星

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VAMp2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

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Cellular & Molecular Immunology 2018年第4期15卷 353-366页

作者： Laura Gómez-Jaramillo Raquel Romero-García Gema Jiménez-Gómez Lisa Riegle Ana Belén Ramos-Amaya JoséAntonio Brieva Marie Kelly-worden Antonio Campos-Caro Unidad de Investigación Hospital Universitario Puerta del MarCádizSpain Department of Biology Ball State UniversityMuncieINUSA

The production and secretion of antibodies by human plasma cells(pCs)are two essential processes of humoral *** secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors(SNAREs),which are located in the plasma membrane(t-SNAREs)and in the antibody-carrying vesicle membrane(v-SNARE),and mediate the fusion of both *** have previously shown that SNAp23 and STX4 are the t-SNAREs responsible for antibody ***,using human pCs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMp)isoforms,demonstrating that all isoforms(with the exception of VAMp1)are expressed by the referenced ***,the functional role in antibody secretion of each expressed VAMp isoform was tested using *** results show that VAMp2 may be the v-SNARE involved in vesicular antibody *** further support this conclusion,we used tetanus toxin light chain to cleave VAMp2,conducted experiments to verify co-localization of VAMp2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMp2 with STX4 and SNAp23 and the in situ interaction of VAMp2 with *** together,these findings implicate VAMp2 as the main VAMp isoform functionally involved in antibody secretion.

关键词： exocytosis human immunoglobulin plasma cells VAMp proteins

Hypoglycemia, Hyperglycemia and Astaxanthin: An <i>in Vitro</i>Alzheimer’s Disease Model

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Advances in Alzheimer's Disease 2019年第3期8卷 27-38页

作者： Julie Griffith Shauna Northrup Emma Cieslik Marie Kelly-worden Biology Department Ball State University Muncie USA

Alzheimer’s Disease is projected to increase to 30 million people in the next 30 years and the rate of diabetes mellitus is projected to rise also. Hyperglycemia is commonly observed in patients with diabetes mellitus, and hypoglycemia is a common consequence due to insulin therapy. previous research has shown a potential link between Alzheimer’s disease and diabetes. This study sought to determine if Astaxanthin (ATX) could prevent mitochondrial dysfunction from the compounded effects of amyloid β (Aβ) plaque and hypoglycemia or hyperglycemia. Growth patterns, ATp production, and ROS generation were examined in 2 μM, 5 μM, 25 μM (hypoglycemic groups), 2 mM, 5 mM (normal groups), and 25 mM glucose (hyperglycemic group), and then treated with or without ATX or Aβ. when hypoglycemia groups and the hyperglycemia group were treated with ATX, their growth patterns were either comparable to control or increased. ATX and Aβ treated cells demonstrated increased growth patterns over cells treated with Aβ alone. Aβ alone treated groups overall had significantly less growth than controls (p β demonstrated low levels of average fluorescence generated by ROS production as determined by MitoSox assay while ATX groups actually produced higher to normal levels of ROS. Cells grown in the presence of Aβ and ATX generally produced more ROS than just Aβ groups. Thus, hypoglycemia and hyperglycemia do appear to compound the effects of Aβ on hippocampal cells. ATX treatment demonstrated promise with increased cellular growth, which promoted usage of ATp by the cell and ROS production. This growth was present even in the presence of Aβ, suggesting that ATX is able to overcome the negative effects of Aβ.

关键词： ATp Luciferase Assay ROS production Amyloid Beta Astaxanthin Diabetes Mellitus

怎样才能成功地钻凿天井导向孔并减少偏斜(二)

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国外金属矿采矿 1980年第7期 56-63页

作者： E.p.worden 刘汉贵

多年来,对旋转钻进水力学的研究,特别是在矿业方面,主要是为了解决排除孔底的钻粉问题。重点是研究流体通过钻杆外壁同孔壁之间的环状空隙的流动规律。可是最近钻孔水力学问题,已经分成两个研究领域。一个是象上面所说的从钻孔排除粉尘... 详细信息

多年来,对旋转钻进水力学的研究,特别是在矿业方面,主要是为了解决排除孔底的钻粉问题。重点是研究流体通过钻杆外壁同孔壁之间的环状空隙的流动规律。可是最近钻孔水力学问题,已经分成两个研究领域。一个是象上面所说的从钻孔排除粉尘。另一个是有效地冲洗孔底。已发表的研究资料表明,只要在孔底积

关键词：天井钻机环隙炮孔露天矿压降英尺/分钻具反井钻机掘进机械炮眼矿山稳杆器导向孔钻凿

怎样才能成功地钻凿天井导向孔并减少偏斜(一)

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矿业工程 1980年第6期 60-64+55页

作者： E.p.worden 刘汉贵

保持天井导向孔钻进方向的准确性并防止其偏斜,比提高钻孔速度,降低成本更为重要,因为,为了降低成本而进行高速钻孔,往往会造成钻孔偏离“孔标”(target)的严重后果。目前大多数其他钻进作业都致

关键词：牙轮钻头导向孔天井矿井软岩层钻头结构轴颈角硬岩层稳杆器钻具钻凿

Streptococcal Antibody probe Crosses the Blood Brain Barrier and Interacts within the Basal Ganglia

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Open Journal of pathology 2015年第2期5卷 42-49页

作者： Robyn Gebhard Courtney Huff Mathew Osborne Lisa Riegle Marie Kelly-worden Department of physiology and Health Science Ball State University Muncie USA

within the brain, the basal ganglia (basal nuclei) regulates wanted movement and inhibits unwanted movement. This area of the brain is intertwined with capillary beds that bring nutrients to the brain and form the blood brain barrier. During disease state, antibodies are increased in circulation and movement of these antibodies into the basal ganglia can occur. Streptococcal infection can lead to the generation of antibodies that have autoimmune activity within the brain. These antibodies have been implicated in neurological disorders. In our laboratory, an in vitro study of a monoclonal mouse antibody generated against the class 1 epitope of the M6 protein has demonstrated binding within the basal ganglia of Lewis rat brains. Here we present an in vivo study using Lewis rats injected with either the streptococcal antibody or an anti-myosin positive control. The interaction and movement of the antibody from blood vessels into the tissues of the basal ganglia was determined through the use of immunofluorescence and fluorescent microscopy and is contrasted with IgG injected and uninjected controls. Our data demonstrates that the streptococcal antibody penetrates the blood brain barrier within 24 hours (as determined by the presence of immunofluorescence outside of blood vessels) and remains significantly elevated above control values even 72 hours after injection (p positive control was not visualized in the interstitial fluid until 48 hours post injection and was no longer significantly above control levels by 72 hours. IgG injected controls did not display movement of antibody into the brain. Therefore, the streptococcal antibody is capable of crossing the blood brain barrier and interacting with tissues of the basal ganglia.

关键词： Blood Brain Barrier Antibodies Basal Ganglia Streptococcus Rat

Spatial distribution of leprosy in India:an ecological study

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Infectious Diseases of poverty 2018年第1期7卷 206-214页

作者： Kyra H.Grantz winnie Chabaari Ramolotja Kagiso Samuel Buri Gershom Laura Blum Lee worden Sarah Ackley Fengchen Liu Thomas M.Lietman Alison p.Galvani Lalitha prajna Travis C.porco Department of Biology University of FloridaGainesvilleFLUSA Emerging pathogens Institute University of FloridaGainesvilleFLUSA DST/NRF Center for Excellence in Epidemiological Modeling and Analysis(SACEMA) StellenboschSouth Africa Stellenbosch University StellenboschSouth Africa African Institute of Mathematical Sciences MuizenbergSouth Africa University of California BerkeleyCAUSA Francis I.proctor Foundation for Research in Ophthalmology University of CaliforniaSan FranciscoCAUSA Department of Ophthalmology University of CaliforniaSan FranciscoCAUSA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCAUSA Yale University New HavenCTUSA Aravind Eye Hospital MaduraiTamil NaduIndia

Background:As leprosy elimination becomes an increasingly realistic goal,it is essential to determine the factors that contribute to its *** evaluate social and economic factors as predictors of leprosy annual new case detection rates within India,where the majority of leprosy cases ***:we used correlation and linear mixed effect regressions to assess whether poverty,illiteracy,nighttime satellite radiance(an index of development),and other covariates can explain district-wise annual new case detection rate and Grade 2 disability ***:we find only weak evidence of an association between poverty and annual new case detection rates at the district level,though illiteracy and satellite radiance are statistically significant predictors of leprosy at the district *** find no evidence of rapid decline over the period 2008-2015 in either new case detection or new Grade 2 ***:Our findings suggest a somewhat higher rate of leprosy detection,on average,in poorer districts;the overall effect is *** divide between leprosy case detection and true incidence of clinical leprosy complicates these results,particularly given that the detection rate is likely disproportionately lower in impoverished *** information is needed to distinguish the determinants of leprosy case detection and transmission during the elimination epoch.

关键词： Leprosy Hansen’s disease India poverty Spatial

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