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Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma

World Journal of Gastroenterology 2008年第7期14卷 1044-1052页

作者： Paras Jethwa Mushal Naqvi Robert G Hardy neil A Hotchin Sally Roberts Robert Spychal Chris Tselepis CRUK Institute for Cancer Studies University of BirminghamUnited Kingdom Department of Clinical and Surgical Sciences Royal Infirmary of EdinburghUnited Kingdom School of Biosciences University of BirminghamUnited Kingdom Sandwell and West Birmingham Hopsitals NHS Trust BirminghamUnited Kingdom

AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. The effect of Slug on epithelial mesenchymal transition (EMT) markers was examined by transfection of Slug into an adenocarcinoma line ***: Cellular localisation of Slug in Barrett's metaplasia was largely cytoplasmic whilst in adenocarcinoma it was nuclear. Semi-quantitative analysis indicated that Slug was more abundant in adenocarcinoma compared to matched Barrett's metaplastic specimens. Snail and Twist were expressed in adenocarcinoma but were cytoplasmic in location and not induced compared to Barrett's mucosa. These observations were supported by mRNA studies where only Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression. Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and ***: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.

关键词： Slug Oesophagus Cancer Barrett's metaplasia Epithelial-mesenchymal transition

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Atypical organic dyes used as sensitizers for efficient dye-sensitized solar cells

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Frontiers of Optoelectronics 2016年第1期9卷 38-43页

作者： Yue Hu neil Robertson School of Chemistry University of Edinburgh Edinburgh EH9 3F J UK

Since their invention, dye-sensitized solar cells （DSSCs） have received enormous research attention from scientists with different background due to the possibility of low-cost production and fabrication on flexible substrates. One of the most important components in DSSCs is the sensitizing dye, including metal-complexes and metal-free organic dyes. The donor-π bridge-acceptor （D-π-A） structure is the mainstream in the design of organic sensitizers because it facilitates efficient chargetransfer toward the Ti02 upon excitation. However, some sensitizers that do not follow this structure, or have some modification upon this structure, also present good efficiency when applied in DSSC devices. This review summarizes these atypical dyes in order to inspire more diverse designs toward highly efficient DSSCs.

关键词： donor- acceptor-π bridge-acceptor (D-A-π-A),donor-free di-anchoring

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Long-term, in vivo therapeutic effects of a single dose of miR-145 micelles for atherosclerosis

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Bioactive Materials 2023年第9期27卷 327-336页

作者： Deborah D.Chin neil Patel Woori Lee Sonali Kanaya Jackson Cook Eun Ji Chung Department of Biomedical Engineering University of Southern CaliforniaLos AngelesCA90089United States Division of Vascular Surgery and Endovascular Therapy Department of SurgeryKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Mork Family Department of Chemical Engineering and Materials Science University of Southern CaliforniaLos AngelesCA90089United States Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Division of Nephrology and Hypertension Department of MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Norris Comprehensive Cancer Center Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90089United States

Atherosclerosis is a chronic inflammatory disease that is characterized by the build-up of lipid-rich plaques in the arterial walls. The standard treatment for patients with atherosclerosis is statin therapy aimed to lower serum lipid levels. Despite its widespread use, many patients taking statins continue to experience acute events. Thus, to develop improved and alternative therapies, we previously reported on microRNA-145 (miR-145 micelles) and its ability to inhibit atherosclerosis by targeting vascular smooth muscle cells (VSMCs). Importantly, one dose of miR-145 micelles significantly abrogated disease progression when evaluated two weeks post-administration. Thus, in this study, to evaluate how long the sustained effects of miR-145 micelles can be maintained and towards identifying a dosing regimen that is practical for patients with chronic disease, the therapeutic effects of a single dose of miR-145 micelles were evaluated for up to two months in vivo. After one and two months post-treatment, miR-145 micelles were found to reduce plaque size and overall lesion area compared to all other controls including statins without causing adverse effects. Furthermore, a single dose of miR-145 micelle treatment inhibited VSMC transdifferentiation into pathogenic macrophage-like and osteogenic cells in plaques. Together, our data shows the long-term efficacy and sustained effects of miR-145 micelles that is amenable using a dosing frequency relevant to chronic disease patients.

关键词： MicroRNA-145 Atherosclerosis Vascular smooth muscle cell Nanoparticle Gene therapy

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Hepatic lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease

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World Journal of Gastroenterology 2010年第40期16卷 5065-5069页

作者： Hongfa Zhu Henry C Bodenheimer David J Clain Albert D Min neil D Theise Department of Pathology Mount Sinai School of MedicineNewYorkNY10029United States Department of Medicine (Divisions of Digestive Diseases)Beth Israel Medical Center Albert Einstein College of Medicine Department of Pathology Beth Israel Medical CenterAlbert Einste in College of MedicineNew YorkNY 10003United States

AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, lipogranuloma can also be used as a marker of prior hepatic steatosis.

关键词： Lipogranuloma Hepatitis C Fatty liver disease Steatosis Steato-fibrosis

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Whipple’s operation with a modified centralization concept:A model in low-volume Caribbean centers

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World Journal of Clinical Cases 2022年第22期10卷 7620-7630页

作者： Shamir O Cawich neil W Pearce Vijay Naraynsingh Parul Shukla Rahul R Deshpande Department of Clinical Surgical Sciences University of the West IndiesSt Augustine 000000Trinidad and Tobago University Surgical Unit Southampton General HospitalSouthampton SO166YDUnited Kingdom Department of Surgery Weill Cornell Medical CollegeNew YorkNY 10065United States Department of Surgery Manchester Royal InfirmaryManchester M139WLUnited Kingdom

Conventional data suggest that complex operations,such as a pancreaticoduodenectomy(PD),should be limited to high volume ***,this is not practical in small,resource-poor countries in the *** these settings,patients have no option but to have their PDs performed locally at low volumes,occasionally by general *** this paper,we review the evolution of the concept of the high-volume center and discuss the feasibility of applying this concept to low and middle-income ***,we discuss a modification of this concept that may be considered when incorporating PD into low-volume and resource-poor countries,such as those in the *** paper has two ***,we performed a literature review evaluating studies published on outcomes after PD in high volume *** data in the Caribbean is then examined and we discuss the incorporation of this operation into resource-poor hospitals with modifications of the centralization *** the authors’opinions,most patients who require PD in the Caribbean do not have realistic opportunities to have surgery in high-volume centers in developed *** these settings,their only options are to have their operations in the resource-poor,low-volume settings in the ***,post-operative outcomes may be improved,despite low-volumes,if a modified centralization concept is encouraged.

关键词： Pancreas Surgery Pancreatectomy Whipple’s Pancreaticoduodenectomy

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Degenerative meniscus: Pathogenesis, diagnosis, and treatment options

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World Journal of Orthopedics 2014年第5期5卷 597-602页

作者： Richard Howell neil S Kumar Nimit Patel James Tom Department of Orthopedic Surgery Drexel University College of Medicine Hahnemann University Hospital

The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive Mc Murray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on nonsteroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients re-fractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well.

关键词： Meniscus Degenerative joint disease Meniscal tear Osteoarthritis Arthroscopy

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Relativistic Effects in the Global Positioning System

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Journal of Systems Engineering and Electronics 1995年第4期6卷 199-237页

作者： neil Ashby (Department of Physics, University of Colorado, Boulder, Colorado 80309-0390 USA) Department of Physics University of Colorado Boulder Colorado 80309-0390 USA

The Global Positioning System (GPS) uses accurate atomic clocks in satellites and on the ground to provide world-wide position and time determination. These clocks have gravitational and motional frequency shifts which are so large that, without properly accounting for relativistic effects, the system would not work. As a practical matter, therefore, many individuals who use the GPS need to understand how relativistic effects accounted for in the system. This paper discusses relativistic effects arising from both special relativity and general relativity, and how these effects are incorporated in GPS operations. Two introductory sections on kinematics in special and general relativity, respectively, are followed by a section which describes how relativistic effects should be accounted for. The concept of synchroization in the Earth-Centered Inertial frame is discussed in detail. Numerical and experimental examples are given, showing the sizes of the various effects. The treatment of special and general relativity is sufficiently complete that a person should be able to follow the development without much reference to external material, except that a few standard results have been quoted from textbooks without derivation.

关键词： Relativity Global positioning system Sagnac effect Synchronization.

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Virtual-reality and intelligent hardware in digital twins

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Virtual Reality & Intelligent Hardware 2022年第6期4卷 I0001-I0003页

作者： Zhihan LV Gustavo MARFIA Fabio POIESI neil VAUGHAN Jun SHEN Uppsala University Sweden University of Bologna Italy Fondazione Bruno Kessler Italy University of Exeter UK University of Wollongong Australia

Several new models and formats for the digital transformation of the manufacturing industry appear because of the rapid integration of information technology and the real economy,as well as the increasingly obvious evolution trend of industrial digitalization,networking,and *** them,digital twins have increasingly become a research hotspot in all sectors of the industry and have broad *** maps physical objects in virtual space in a digital way and simulates their behavioral characteristics in real *** makes the gap between virtuality and reality disappear based on their closed-loop *** twins are undoubtedly an important and strategic technology in response to familiar products,production,and *** can also speculate some indicators that cannot be directly measured by machine learning through collecting the direct data of limited physical sensor *** can realize an assessment of the current state,a diagnosis of past problems,and a prediction of future trends,and simulate possibilities to provide more comprehensive decision support.

关键词： hardware doubt prediction

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Rapid divergent coevolution of Sinopotamon freshwater crab genitalia facilitates a burst of species diversification

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Integrative Zoology 2020年第3期15卷 174-186页

作者： Fengxin YAO Boyang SHI Xiaoqi WANG Da PAN Ming BAI Jie YAN neil CUMBERLIDGE Hongying SUN Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjingChina Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijingChina Department of Biology Northern Michigan UniversityMarquetteMichiganUSA

One of the most striking radiations in brachyuran evolution is the considerable morphological diversification of the external reproductive structures of primary freshwater crabs:the male first gonopod(G1)and the female vulva(FV).However,the lack of quantitative studies,especially the lack of data on female genitalia,has seriously limited our understanding of genital evolution in these *** we examined 69 species of the large Chinese potamid freshwater crab genus Sinopotamon Bott,1967(more than 80%of the described species).We used a landmark-based geometric morphometric approach to analyze variation in the shape of the G1 and FV,and to compare the relative degree of variability of the genitalia with non-reproductive structures(the third maxillipeds).We found rapid divergent evolution of the genitalia among species of Sinopotamon when compared to non-reproductive *** addition,the reconstruction of ancestral groundplans,together with plotting analyses,indicated that the FV show the most rapid divergence,and that changes in FV traits correlate with changes in G1 *** we provide new evidence for coevolution between the male and female external genitalia of Sinopotamon that has likely contributed to rapid divergent evolution and an associated burst of speciation in this lineage.

关键词： coevolution genital diversification freshwater crab morphological evolution

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Molecular basis for the inhibition of β-hydroxyacyI-ACP dehydratase HadAB complex from Mycobacterium tuberculosis by flavonoid inhibitors

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Protein & Cell 2015年第7期6卷 504-517页

作者： Yu Dong Xiaodi Qiu neil Shaw Yueyang Xu Yuna Sun Xuemei Li Jun Li Zihe Rao National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049China Structure Biology Laboratory Tsinghua University Beijing 100084 China Tianjin Key Laboratory of Protein Science College of'Life Sciences Nankai University Tianjin 300071 China

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobac- terium tuberculosis （Mtb）. Consequently, stalling dehy-dration cures tuberculosis （TB）. Clinically used anti-TB drugs like thiacetazone （TAC） and isoxyl （ISO） as well as flavonoids inhibit the enzyme activity of the β-hydroxy- acyI-ACP dehydratase HadAB complex. How this inhi- bition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2＇,4,4＇-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon muta- tion to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site, The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs,

关键词： Mycobacterium tuberculosis hotdog fold,mycolic acid dehydratase flavonoid thiacetazone isoxyl

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