bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3893: Endocan is upregulated on tumor vessels in invasive bladder cancer and mediates VEGF-A-induced angiogenesis.
Authors: Roudnicky Filip , Poyet Cedric , Wild Peter J. , Krampitz Sarah , Negrini Fabrizia , Huggenberger Reto , Rogler Anja , Stöhr Robert , Hartmann Arndt , Provenzano Maurizio , Otto Vivianne I. , Detmar Michael 
Published: August 2014

Abstract
Tumor-associated blood vessels differ from normal vessels at the morphological and molecular level. Proteins that are only present on tumor vessels may serve as biomarkers and as therapeutic targets for inhibition of angiogenesis in cancer. To identify factors contributed by the tumor-associated endothelium, we performed immuno-laser capture microdissection (i-LCM) of blood vascular endothelial cells in conjunction with transcriptional profiling from surgically harvested cancer and normal matched bladder tissue of five patients with invasive bladder cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer and from normal bladder tissue, we found that endocan (endothelial cell-specific molecule-1) was highly elevated on tumor vessels and associated with the filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably, endocan expression on tumor vessels strongly correlated with the tumor stage and invasiveness and predicted a shorter recurrence-free survival time in non-invasive bladder cancers. Furthermore, both endocan and VEGF-A levels were significantly higher in plasma of patients with invasive bladder cancer (n=53) compared to healthy individuals (n=60). Using cultured blood vascular endothelial cells and an in vivo transgenic mouse model we found that endocan expression was strongly upregulated by VEGF-A activation of VEGFR-2. RNA interference-mediated knockdown of endocan in cultured blood vascular endothelial cells revealed that endocan was required for the promotion of cell migration and tube formation by VEGF-A. Furthermore, we found that endocan potentiates VEGFR-2 phosphorylation in response to VEGF-A. Therefore, blocking the interaction of endocan with either VEGFR-2 or VEGF-A might represent a promising approach for inhibiting tumor angiogenesis. Endocan might also serve as a novel biomarker for monitoring disease progression and the efficacy of VEGF-A-targeting therapies in patients with bladder cancer.
Citation Format: Filip Roudnicky, Cedric Poyet, Peter J. Wild, Sarah Krampitz, Fabrizia Negrini, Reto Huggenberger, Anja Rogler, Robert Stöhr, Arndt Hartmann, Maurizio Provenzano, Vivianne I. Otto, Michael Detmar. Endocan is upregulated on tumor vessels in invasive bladder cancer and mediates VEGF-A-induced angiogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3893. doi:10.1158/1538-7445.AM2013-3893
Abstract 4238: BROMOscan - a high throughput, quantitative ligand binding platform identifies best-in-class bromodomain inhibitors from a screen of mature compounds targeting other protein classes.
Authors: Quinn Elizabeth , Wodicka Lisa , Ciceri Pietro , Pallares Gabriel , Pickle Elyssa , Torrey Adam , Floyd Mark , Hunt Jeremy , Treiber Daniel 
Published: August 2014

Abstract
Post-translationally appended acetyllysine marks on histone tails are key regulatory features of the epigenetic code. Bromodomains are “readers” of this specific lysine acetylation code, playing an important role in chromatin remodeling and regulation of gene expression. Bromodomains have emerged as an important new druggable target class in small-molecule inhibitor drug discovery, and several bromodomain-containing proteins have been associated with disease. There are 57 bromodomains contained in 41 different proteins; however, few small molecule bromodomain inhibitors have been reported. One primary factor limiting the discovery of new inhibitors is the absence of a comprehensive biochemical bromodomain screening platform. Here we describe the application of DiscoveRx Corporation's proven ligand binding assay technology (KINOMEscan) to the development of quantitative ligand binding assays for human bromodomains (BROMOscan). We have developed a carefully validated assay panel that covers &gt;30 percent of the human bromodomain family, and this panel is suitable for HTS, selectivity profiling, and quantitative affinity (Kd) assessment. We have used this panel internally to identify novel bromodomain inhibitors and, remarkably, have demonstrated that known, mature inhibitors thought to be selective for targets from other protein families have best in class affinity for bromodomains as well. These data shall be presented, as will a description of the BROMOscan panel replete with extensive assay validation data.
Citation Format: Elizabeth Quinn, Lisa Wodicka, Pietro Ciceri, Gabriel Pallares, Elyssa Pickle, Adam Torrey, Mark Floyd, Jeremy Hunt, Daniel Treiber. BROMOscan - a high throughput, quantitative ligand binding platform identifies best-in-class bromodomain inhibitors from a screen of mature compounds targeting other protein classes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4238. doi:10.1158/1538-7445.AM2013-4238
Abstract 5066: Matriptase mediated signaling in breast cancer.
Authors: Zoratti Gina L. , Bergum Christopher , Boerner Julie L. , List Karin 
Published: August 2014

Abstract
Historically proteases have been associated with tumor progression and metastasis through degradation of the basement membrane. In recent years these enzymes have also been shown to play key roles in the activation of growth factors and cytokines, thereby activating pro-oncogenic signaling pathways. Matriptase is an epithelia-specific pericellular protease which has received considerable attention recently spurred by its consistent dysregulation in human epithelial tumors including breast cancer. Several institutions are currently developing small and large molecule inhibitors of matriptase, however thus far no studies have been published focusing on the role of matriptase in breast cancer growth and progression. Presently we do not know whether matriptase plays a causal or promotional role in breast carcinogenesis and therefore its potential as an anti-cancer drug target is still unexplored. In the following study we will perform both functional and mechanistic studies of matriptase in breast cancer using parallel, complementary in-vitro and in-vivo genetic “loss-of-function” strategies. Matriptase efficiently cleaves pro-hepatocyte growth factor (pro-HGF) into active HGF, the cognate ligand of the proto-oncogene tyrosine kinase receptor c-Met, and thereby elicits pro-tumorigenic downstream signaling events. Both c-Met and matriptase are expressed on the surface of mammary epithelial cells and breast carcinoma cells, whereas the c-Met ligand and matriptase proteolytic target pro-HGF is secreted by stromal fibroblasts thus defining a paracrine growth factor activation and signaling mechanism. Our goal with this project is to determine whether matriptase is a novel target which could provide an opportunity for developing improved breast cancer intervention drugs in the future.
Citation Format: Gina L. Zoratti, Christopher Bergum, Julie L. Boerner, Karin List. Matriptase mediated signaling in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5066. doi:10.1158/1538-7445.AM2013-5066
Abstract 5138: Structural insights into the dynamic functionality of Bax through molecular dynamics simulations.
Authors: Khaled Annette , Boohaker Rebecca , Finch Craig , Tafur Sergio 
Published: August 2014

Abstract
The Bcl-2 protein family modulates the balance between cellular life and death. Bax, a pro-apoptotic member of this family, participates in mitochondria-mediated apoptosis but also supports mitochondrial bioenergetics. In previous work, we showed that a peptide derived from the alpha 9-helix of Bax is cytotoxic, specifically when used to treat breast cancer cells. Such structural and biochemical studies are useful for identifying functional domains within Bax that can be developed into therapeutic peptides, but are limiting when ascribing function to domains at a molecular level. Computational modeling and molecular dynamics simulations of Bax provides a high-power analysis of the subtle changes that modulate the regulatory and effector activities of the protein. This study seeks to elucidate the consequence of alterations in micro-domains that confer activity, apoptotic or otherwise, to the protein. Molecular dynamics simulation was used to determine how the trans-membrane region of Bax conferred stability to the protein, identifying regions of high flexibility and differential exposure. Computationally rotating the Ψ angle at Pro168 altered the position of the α9-helix of Bax, mimicking the “active” and “inactive” forms of Bax. We found that “active” Bax, but not “inactive” Bax, presented a more relaxed structure which altered the conformation and exposure of the BH3 domain, potentially enhancing interactions among the family of Bcl-2 proteins. Since dysregulation of Bcl-2 proteins is implicated in a number of cancers, examining the basic structural dynamics at a molecular level yielded information that can aid in the design novel Bcl-2 family-targeting chemotherapeutics.
Citation Format: Annette Khaled, Rebecca Boohaker, Craig Finch, Sergio Tafur. Structural insights into the dynamic functionality of Bax through molecular dynamics simulations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5138. doi:10.1158/1538-7445.AM2013-5138
Abstract 91: Powerful inhibition of human renal cell carcinomas with antagonists of growth hormone-releasing hormone (GHRH): a preclinical study.
Authors: Rick Ferenc G. , Abi-Chaker Andrew , Szalontay Luca , Block Norman L. , Halmos Gabor , Nadji Mehrdad , Schally Andrew V. 
Published: August 2014

Abstract
BACKGROUND: Advances in targeted medical thereapy has demonstrated improved clinical outcomes for patients with metastatic renal cell carcinoma (RCC), however, a complete response is rare and current therapy has various adverse effects that are unfortunately not as rare. Early antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit experimental RCC cell line, Caki-1, in vitro and in vivo. GHRH itself acts as an autocrine/paracrine growth factor in human cancers, including RCC. Herein, we investigate the effects of novel and highly potent new antagonists of GHRH on the growth of three RCC cell lines with different primary tumor sites.
METHODS: The expression of GHRH receptor in all three cell lines was evaluated by ligand competition studies. The in vitro influence of GHRH antagonists designated MIA-602, MIA-604, MIA-606 and MIA-690 on cell viability was assessed by MTS assay in ACHN, A498, and 786-0 human RCC cells. GHRH antagonists were given at a dose of 5μg daily in these three nude-mice xenograft models in vivo. Cell cycle parameters were analyzed by laser flow cytometry.
RESULTS: Ligand competition studies revealed specific, high affinity binding sites for GHRH receptor in all three RCC cell lines. GHRH antagonists inhibited the proliferation of all three RCC cells in a dose dependent manner. GHRH antagonists caused significant inhibition of tumor growth of ACHN, A498, and 786-0 RCCs ranging from 53-75% after 35 days of treatment (p&lt;0.001). Treatment of ACHN and A498 cells with 10μM MIA-602 and MIA-690 (5 and 10μM) led to a significant increase in number of cells with subG1 DNA content, suggesting apoptosis.
CONCLUSIONS: The effectiveness of the new and novel GHRH antagonists in inhibiting growth of experimental RCC models in vitro and in vivo was demonstrated. The inhibitory effect of GHRH antagonists is mainly due to direct suppressive effects exerted through GHRH receptors. Further biochemical and histological evaluation is warranted to explore the mechanisms of action of GHRH antagonists in RCC.
Citation Format: Ferenc G. Rick, Andrew Abi-Chaker, Luca Szalontay, Norman L. Block, Gabor Halmos, Mehrdad Nadji, Andrew V. Schally. Powerful inhibition of human renal cell carcinomas with antagonists of growth hormone-releasing hormone (GHRH): a preclinical study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 91. doi:10.1158/1538-7445.AM2013-91
Abstract LB-309: Non-covalent wild-type-sparing inhibitors of EGFR T790M .
Authors: Lee Ho-June , Schaefer Gabriele , Heffron Tim , Malek Shiva , Merchant Mark , Yauch Robert L. , Pirazzoli Valentina , Politi Katerina , Settleman Jeff 
Published: August 2014

Abstract
Non-small cell lung cancers (NSCLC) with activating EGFR mutations respond well to the selective EGFR kinase inhibitors, gefitinib and erlotinib. Despite initial responses, most patients relapse within one year due to acquired resistance. Approximately half of these cases are associated with a secondary EGFR kinase domain mutation, T790M–the “gatekeeper” mutation. Irreversible EGFR kinase inhibitors have demonstrated pre-clinical efficacy toward EGFR T790M and have been undergoing clinical evaluation. However, the current irreversible inhibitors have yet to yield clinical activity in this setting, possibly due to dose-limiting toxicities. In a cancer cell line screening effort, we identified the PKC inhibitor, Go6976, a staurosporine derivative, as an inhibitor of EGFR mutant-driven NSCLC cells. Further analysis revealed that Go6976 potently suppresses both autophosphorylation and ligand-induced phosphorylation of EGFR mutants including T790M. Among some structurally-related bis-indole-based compounds currently undergoing clinical testing, PKC412, a FLT3 kinase inhibitor, demonstrated -100 fold greater potency against EGFR T790M than Go6976. Interestingly, while irreversible inhibitors are less potent against EGFR T790M than either EGFR WT or EGFR activating mutants, the bis-indole-based compounds show substantially greater potency against EGFR T790M, effectively sparing WT EGFR. Our findings suggest that this class of reversible inhibitors may be more effective and better tolerated than irreversible inhibitors to overcome EGFR T790M-mediated acquired drug resistance in NSCLC.
Citation Format: Ho-June Lee, Gabriele Schaefer, Tim Heffron, Shiva Malek, Mark Merchant, Robert L. Yauch, Valentina Pirazzoli, Katerina Politi, Jeff Settleman. Non-covalent wild-type-sparing inhibitors of EGFR T790M . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-309. doi:10.1158/1538-7445.AM2013-LB-309
A Smart Image-Based Cloud Detection System for Intrahour Solar Irradiance Forecasts
Authors: Chu Yinghao , Pedro Hugo T. C. , Nonnenmacher Lukas , Inman Rich H. , Liao Zhouyi , Coimbra Carlos F. M. 
Published: August 2014

AbstractThis study proposes an automatic smart adaptive cloud identification (SACI) system for sky imagery and solar irradiance forecast. The system is deployed using off-the-shelf fish-eye cameras that offer substantial advantages in terms of cost when compared to industry-standard sky imagers. SACI uses a smart image categorization (SIC) algorithm that combines the sky images and solar irradiance measurements to classify sky conditions into three categories: clear, overcast, and partly cloudy. A cloud detection scheme, optimized for each image category, is used to quantify cloud cover from the sky images. SACI is optimized and validated against manually annotated images. Results show that SACI achieves overall classification accuracy higher than 90% and outperforms reference cloud detection methods. Cloud cover retrieved by SACI is used as an input for an artificial neural network (ANN) model that predicts 1-min average global horizontal irradiance (GHI), 5-, 10-, and 15-min ahead of time. The performance of the ANN forecasting model is assessed in terms of common error statistics (mean bias and root-mean-square error) and in terms of forecasting skill over persistence. The model proposed in this work achieves forecasting skills above 14%, 18%, and 19% over the persistence forecast for 5-, 10-, and 15-min forecasts, respectively.
Experimentally Based Estimates of Relations between X-Band Radar Signal Attenuation Characteristics and Differential Phase in Rain
Authors: Matrosov Sergey Y. , Kennedy Patrick C. , Cifelli Robert 
Published: August 2014

AbstractCorrecting observed polarimetric radar variables for attenuation and differential attenuation effects in rain is important for meteorological applications involving measurements at attenuating frequencies such as those at X band. The results of estimating the coefficients in the correction-scheme relations from dual-wavelength polarimetric radar measurements of rainfall involving attenuating and nonattenuating frequencies are described. Such coefficients found directly from measurements are essentially free from different assumptions about drop shapes, drop size distributions, and/or relations between different radar variables that are typically used in many attenuation and differential attenuation correction schemes. Experimentally based estimates derived using dual-wavelength radar measurements conducted during a project in northern Colorado indicate values of the coefficients in the attenuation–differential phase quasi-linear relations at X band in the approximate range of 0.20–0.31 dB deg−1. The corresponding coefficients in the differential attenuation–differential phase relations are in the range of 0.052–0.065 dB deg−1.
Analysis of Mandibular Structure Using 3D Facial Computed Tomography
Authors: Jung Su Young , Shin Seung Youp , Lee Kun Hee , Eun Young Gyu , Lee Young Chan , Kim Sung Wan 
Published: August 2014

ObjectiveThis study measured and analyzed the position and dimension of genial tubercle (GT) and mental foramen (MF)Study DesignRetrospective chart review study.SettingTertiary care teaching hospital.Subjects and MethodsTwo hundred ten subjects were included who received 3‐dimensional (3D) facial computed tomography (CT), and the GT and MF were evaluated. Subjects were divided into 4 groups by gender and skeletal type. Seven variables were measured: (1) height of GT (GTH), (2) width of GT (GTW), (3) distance from apices of lower incisors to superior border of GT (LI‐SGT), (4) distance from inferior border of GT to inferior border of mandible (IGT‐IBM), (5) thickness of anterior mandible (MT), (6) distance from symphysis of mandible to MF (S‐MF), and (7) distance from superior border of GT to inferior border of mandible (SGT‐IBM).ResultsAll the parameters showed marked differences in individuals. Class I males showed longer GTH, MT, and SGT‐IBM than class I females (P <. 05). IGT‐IBM and S‐MF were longer in class II males than in class I females (P <. 05). LI‐SGT and IGT‐IBM also showed personal variation.ConclusionAnatomical features of mandibular structures showed individual variations. GTH, IGT‐IBM, MT, S‐MF, and SGT‐IBM also showed differences between the groups.
Analysis of the scope of cooperative bandwidth sharing among mobile routers in vehicular networks
Authors: Tu Lai , Lin Shih-Yang , Huang Chung-Ming 
Published: August 2014

Abstract
This paper investigates the optimal cooperation scope (OCS) for cooperative bandwidth sharing (CBS) in vehicular networks. An analytical model, which comprises the network model, relay schemes, cost model, and vehicular flow model, is presented. Three relay schemes based on optimal single path relay and opportunistic relay for multi-hop CBS are proposed and studied. The OCS is solved as the maximum physical distance or hops between the bandwidth requester and bandwidth helper in the optimal solution to maximize the CBS benefit. OCSs for different environments and with different relay schemes are given in the paper. The results indicate that the OCS is sensitive to the cost weight and may also be larger when using a proper opportunistic relay-based scheme than when using the optimal single path-based one. The results also show that the vehicular density does not affect the optimal cooperation scope much but can result in different CBS benefit. The model and findings of the relations between OCS and the running environment revealed in this paper can be used as a reference for parameter choosing when designing the CBS system in vehicular networks.
Do Parents Matter? Effects of Lender Affiliation Through the Mortgage Boom and Bust
Authors: Gartenberg Claudine 
Published: August 2014

It is widely acknowledged that the 2007 mortgage crisis was preceded by a broad deterioration in underwriting diligence. This paper shows that this deterioration varied by the industry affiliation of mortgage lenders. Loans issued by homebuilders and stand-alone lenders were significantly less likely to default than loans issued by depository banks and affiliates of major financial institutions. I argue that homebuilders and stand-alone lenders had the least financial capacity to hold mortgages, and their resulting need to sell loans quickly on the secondary market forced them to issue safer loans. Tests of other explanations, including differences in information and incentives to avoid foreclosure externalities, receive little support. This study highlights a novel means by which firm boundaries influence firm adaptation to changing market conditions by defining the boundaries of the internal capital markets and hence the relative constraints of constituent units. This paper was accepted by Bruno Cassiman, business strategy.
The Fixed Charge Transportation Problem: An Exact Algorithm Based on a New Integer Programming Formulation
Authors: Roberti Roberto , Bartolini Enrico , Mingozzi Aristide 
Published: August 2014

The fixed charge transportation problem generalizes the well-known transportation problem where the cost of sending goods from a source to a sink is composed of a fixed cost and a continuous cost proportional to the amount of goods sent. In this paper, we describe a new integer programming formulation with exponentially many variables corresponding to all possible flow patterns to sinks. We show that the linear relaxation of the new formulation is tighter than that of the standard mixed integer programming formulation. We describe different classes of valid inequalities for the new formulation and a column generation method to compute a valid lower bound embedded into an exact branch-and-price algorithm. Computational results on test problems from the literature show that the new algorithm outperforms the state-of-the-art exact methods from the literature and can solve instances with up to 70 sources and 70 sinks. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2014.1947 . This paper was accepted by Dimitris Bertsimas, optimization.