Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye

published_or_final_versio

Modelling Techniques for the Quantification of Some Electron Beam Induced Phenomena

This paper presents simulation models for quantifying the voltage contrast, cathodoluminescence and indirect specimen charging phenomena in the scanning electron microscope (SEM). The voltage contrast model comprises an electric field computation program using the finite-element approach, and a secondary electron trajectory tracking algorithm employing a linear electric field assumption. This trajectory tracking algorithm is more accurate than the conventional electron trajectory tracking algorithms which make use of a constant electric field assumption within each computation step. Using this model, results of qualitative voltage contrast effects on secondary electron trajectories in the specimen chamber of the SEM are shown. This model can also be used for quantitative voltage studies for designing low error voltage energy analysers. The cathodoluminescence (CL) model consists of programs for simulating the electron beam-specimen interaction via Monte Carlo analysis, excess carrier generation and distribution, and optical losses of the CL emission. This model has been used to simulate the CL intensity as a function of surface recombination velocity, diffusion length, and absorption coefficient. A model has also been developed to simulate indirect charging of specimens in the SEM. This model uses the finite-element method to solve for the self-consistent electric field due to the imposed boundary conditions, trapped and moving charges. Secondary electrons are tracked using the trajectory tracking scheme developed

Effect of DMSO on Protein Structure and Interactions Assessed by Collision-Induced Dissociation and Unfolding

Given the frequent use of DMSO in biochemical and biophysical assays, it is desirable to understand the influence of DMSO concentration on the dissociation or unfolding behavior of proteins. In this study, the effects of DMSO on the structure and interactions of avidin and Mycobacterium tuberculosis (Mtb) CYP142A1 were assessed through collision-induced dissociation (CID) and collision-induced unfolding (CIU) as monitored by nanoelectrospray ionization–ion mobility–mass spectrometry (nESI-IM-MS). DMSO concentrations higher than 4% (v/v) destabilize the avidin tetramer toward dissociation and unfolding, via both its effects on charge state distribution (CSD) as well as at the level of individual charge states. In contrast, DMSO both protects against heme loss and increases the stability of CYP142A1 toward unfolding even up to 40% DMSO. Tandem MS/MS experiments showed that DMSO could modify the dissociation pathway of CYP142A1, while CIU revealed the protective effect of the heme group on the structure of CYP142A1.D.S.-H.C. acknowledges the Croucher Foundation and the Cambridge Commonwealth, European and International Trust for receipt of a Croucher Cambridge International Scholarship. M.E.K. was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunc-tion with the Cambridge Commonwealth Trust and Cam-bridge Overseas Trust. K.J.M. and A.G.C. were supported by grants from the UK BBSRC (Biotechnology and Biological Sciences Research Council (BB/I019669/1 and BB/I019227/1)

Paradoxical Impact of Two Folate Receptors, FRα and RFC, in Ovarian Cancer: Effect on Cell Proliferation, Invasion and Clinical Outcome

Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients. © 2012 Siu et al.published_or_final_versio

Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking

2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers

Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.363.postprin

Research Data Supporting Effect of DMSO on Protein Structure and Interactions Assessed By Collision-induced Dissociation and Unfolding

Excel datasheets of raw result

Research Data Supporting Fragment screening against the EthR-DNA interaction by native mass spectrometry

Research Data Supporting Fragment screening against the EthR-DNA interaction by native mass spectrometry. Contains raw data for thermal shift (TS), surface plasmon resonance (SPR) and native MS (nMS) result

Molecular docking for virtual screening of natural product databases

Molecular docking enables the extraordinary structural diversity of natural products to be harnessed in an efficient manner. In this mini-review, we highlight recent examples of the use of molecular docking in virtual screening for the identification of bioactive molecules from natural product databases. © The Royal Society of Chemistry 2011.link_to_subscribed_fulltex