bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-350: In vivo kinome screen reveals potential drivers of brain metastasis
Authors: Lowery Frank J. , Acharya Sunil , Xia Yong , Zhang Chenyu , Saunus Jodi M. , Yu Dihua 
Published: July 2016

Abstract
Brain metastasis remains an unmet medical need, as its incidence continues to rise while treatment options remain palliative. Advances in targeted therapy for breast cancer have prolonged patient survival through better control of the systemic disease, but an ever-increasing number of patients later recur with brain metastasis. As no effective therapies exist for brain metastasis, the median survival of patients is less than one year. To tackle this growing clinical challenge, we sought to better understand the biological mechanism of brain metastasis and to identify novel targets for intervention. We chose to focus on kinases, as they both occupy the central nodes of cancer cell signaling pathways and structurally lend themselves to targeting by small molecules. To identify novel therapeutic targets, we performed an unbiased kinome screen in vivo for determination of brain metastasis driver kinases. We injected MDA-MB-231 human breast cancer cells overexpressing pools of 16-20 kinase ORFs into the carotid artery of nude mice to form experimental brain metastasis. Several of the kinase pools led to decreased brain metastasis-specific survival, decreasing survival time by as much as 50% relative to controls. We then performed targeted next-generation sequencing (NGS) of the pre-and post-injection tumor cells to determine those kinases most enriched in vivo, revealing 31 ORFs that were significantly increased in vivo in multiple animals. To validate the clinical relevance of these potential targets, we examined their expression in a collection of 32 human brain metastases by RNA-seq, and observed that the majority of the ORFs (29/31) were indeed expressed. One of the kinases with the highest in vivo enrichment and expression in human brain metastases was hexokinase 2 (HK2), an important glycolysis regulator that has been previously implicated in brain metastasis and served to validate our findings. Several other candidate kinases were also related to glycolysis and other metabolic pathways, suggesting that these kinases enable metastatic cancer cells to survive in the nutrient-restricted brain environment. Functional validation of these newly identified kinases as true drivers of brain metastasis will reveal whether they have potential to serve as the first targets of brain metastasis-targeted therapy.
Citation Format: Frank J. Lowery, Sunil Acharya, Yong Xia, Chenyu Zhang, Jodi M. Saunus, Dihua Yu. In vivo kinome screen reveals potential drivers of brain metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-350.
Abstract LB-359: Knowledge of prostate cancer and screening attitude of residents of a Nigerian community
Authors: Iweala Emeka E.J , Omonhinmin Conrad A. , Azuh Dominic E. , Okwudi Isioma J. 
Published: July 2016

Abstract
This study assessed the level of awareness and knowledge of prostate cancer amongst the residents of a Nigerian University and its environs. A cross-sectional descriptive study using self-administered questionnaires was carried out among 443 people, aged 20 to 80 residing in Covenant University, Nigeria and its environs. Data analysis was done with SPSS version 15.0. The level of significance was set at p &lt;0.05. The majority (45.1%) of respondents was aged between 31 - 40 years and only 41.3% were aware of the existence of Prostate cancer. Educational background, occupation and religion were observed to significantly increase (p &lt;0.05) awareness of prostate cancer while gender and age did not. The awareness and previous participation in prostate cancer screening negatively (p &lt;0.05) influenced respondents’ decision to participate in future screening. Electronic media via radio and television was the commonest source of awareness for prostate cancer. Only 13.4% became aware through health facility or personnel. Only 30.5% correctly identified the location of the prostate. Most of the respondents identified poor diet and environmental conditions as risk factors while 13.7%, 2.0% and 5.9% identified aging, race and genetics respectively as the causes of prostate cancer. Most of the respondents (31.2%) correctly identified difficult urination as a symptom of prostate cancer. About 30.8% have a relative, family or friend that had prostate cancer out of which 18.5% resulted in deaths. Only one respondent had been previously diagnosed with an enlarged prostate. Majority of the respondents were unaware of a possible cure or therapy. Only 9.9%, of the respondents strongly agreed that prostate cancer was peculiar to all men while a low percentage (4.1%) of respondents strongly agreed that it is a health disparity issue among black men. Over all a very low percentage of 37.9% of the respondents considered prostate cancer to be a serious ailment. The study showed a generally poor knowledge and wrong conceptions about prostate cancer, screening and treatment. This suggests the need for public health education and screening programs on prostate cancer for this population and others.
Citation Format: Emeka E.J Iweala, Conrad A. Omonhinmin, Dominic E. Azuh, Isioma J. Okwudi. Knowledge of prostate cancer and screening attitude of residents of a Nigerian community. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-359.
Abstract NG01: Accumulation of somatic mutations in normal and cancerous tissues with age
Authors: Hoang Margaret L. , Kinde Isaac , Tomasetti Cristian , Rosenquist Thomas , Grollman Arthur P. , Kinzler Kenneth W. , Vogelstein Bert , Papadopoulos Nickolas 
Published: July 2016

Abstract
Fundamental theories in carcinogenesis and aging evoke the accumulation of rare somatic mutations in normal tissues over time. However, absence of a simple and systematic method to characterize somatic mutations in normal tissues precludes the understanding of their functional consequences. We present Bottleneck Sequencing System (BotSeqS), a next-generation sequencing method that quantitates rare somatic point mutations simultaneously across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately before library amplification. Using BotSeqS, we determine the mutation frequencies and spectra in normal brain, kidney, and colon from a total of 34 individuals ranging from &lt; 1 to 98 years old. We show an age and tissue-dependent accumulation of rare point mutations and demonstrate that the somatic mutational burden in normal tissues can vary by several orders of magnitude depending on biological and environmental factors. For example, individuals with defects in the mismatch repair machinery or exposure to environmental carcinogens (smoking, aristolochic acid) show significant increases in mutational frequencies and altered mutational spectra compared to controls. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, we find that the mutational spectra of normal tissues were different from each other but similar to cancers from the same tissue type, suggesting that the differential mutational spectra observed in cancers are tissue-specific rather than cancer-specific. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues.
Citation Format: Margaret L. Hoang, Isaac Kinde, Cristian Tomasetti, Thomas Rosenquist, Arthur P. Grollman, Kenneth W. Kinzler, Bert Vogelstein, Nickolas Papadopoulos. Accumulation of somatic mutations in normal and cancerous tissues with age. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr NG01.
Abstract SY15-03: Drugging “undruggable” transcription factor drivers in cancer
Authors: Bushweller John 
Published: July 2016

Abstract
Dysregulation of gene expression is a hallmark of all cancers. It is critical for conferring stem cell like properties, such as self-renewal and chemo-resistance, on these cancer cells. Such properties contribute to the inability to completely eradicate cancer cells, thereby leading to relapse. The specific gene expression program that confers these properties derives from aberrant activity of specific transcription factors which are drivers of disease. There are numerous examples of such transcription factor drivers in cancer (ERG in prostate cancer, ETV1 in prostate cancer and GIST, RUNX1-ETO and CBFβ-SMMHC in acute myeloid leukemia, etc.). Clearly, the most direct and effective approach to alter this gene expression program is to target the activity of these transcription factors which are drivers of disease. While the paradigm is shifting significantly, transcription factors have traditionally been viewed as “undruggable”. This results from the challenges associated with targeting either the protein-DNA or protein-protein interactions that typically mediate their function. Recent successes in this area are clearly breaking down this paradigm.
Targeting of transcription factors is a very different approach to current approaches to targeted therapy which have heavily focused on kinase inhibitors. Targeting transcription factor drivers will likely alter the stem cell like properties of the cancer cell such as self-renewal, the DNA repair alterations which lead to enhanced rates of mutagenesis, and the chemo-resistance which limits effectiveness of chemotherapy drugs. It is also likely that agents targeting transcription factors will show synergy with appropriately targeted kinase inhibitors.
We have developed a specific, potent, and effective protein-protein interaction inhibitor for the CBFβ-SMMHC fusion protein which is a driver in inv(16) acute myeloid leukemia (Illendula et al. Science 347: 779-784 (2015)). The efficacy of this inhibitor of a critical protein-protein interaction of the CBFβ-SMMHC transcription factor fusion protein clearly demonstrates the utility of directly targeting transcription factor drivers in cancer. Based on this success, we are targeting other transcription factor drivers in leukemia as well as in other cancers. Two examples of our efforts in this area will be presented.
Citation Format: John Bushweller. Drugging “undruggable” transcription factor drivers in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY15-03.
Abstract SY16-02: The discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design
Authors: Fesik Stephen W. 
Published: July 2016

Abstract
Myeloid cell leukemia 1 (Mcl-1) is a member of the Bcl-2 family of proteins that is overexpressed and amplified in a wide variety of cancers and causes resistance to many chemotherapies. Although a very promising cancer target, it exerts its activity through protein-protein interactions and is very challenging to drug with small molecules. Indeed, there are no Mcl-1 inhibitors that have entered clinical trials. In this presentation, I will describe the discovery of picomolar Mcl-1 inhibitors using fragment-based methods and structure-based design that show promise as therapeutic agents for the treatment of heme malignancies and solid tumors.
Citation Format: Stephen W. Fesik. The discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY16-02.
Abstract SY27-02: Targeting leukemia stem cells with small molecule inhibitors of PRC1
Authors: Cierpicki Tomasz 
Published: July 2016

Abstract
Bmi1 is a stem cell gene, which determines the proliferative capacity and self-renewal potential of normal and leukemic stem cells. Multiple studies identified Bmi1 to be able to induce oncogenic transformation and promote tumor growth in a variety of in vitro and in vivo animal models. Bmi1 is a central component of the Polycomb Repressive Complex 1 (PRC1) and interacts with Ring1B protein to form an active E3 ligase, which ubiquitinates histone H2A on lysine K119. This epigenetic modification of H2A is required to maintain transcriptionally repressive state of many genes. Small molecule inhibitors of the Ring1B-Bmi1 E3 ligase activity have not been reported to date, but are highly desired as potential therapeutic agents targeting cancer stem cells. Employing fragment screening approach we identified small molecule inhibitors of Ring1B-Bmi1. Using medicinal chemistry, we developed potent compounds that bind to Ring1B-Bmi1 and inhibit its E3 ubiquitin ligase activity with low micromolar affinities. In cells, Ring1B-Bmi1 inhibitors revealed robust downregulation of H2A K119 ubiquitination. Treatment of model cell lines enriched in leukemia initiating cells show that the Ring1B-Bmi1 inhibitor blocks the self-renewal capacity and induces cellular differentiation. Our approach validates that RING ligases represent novel class of ‘druggable’ epigenetic targets.
Citation Format: Tomasz Cierpicki. Targeting leukemia stem cells with small molecule inhibitors of PRC1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY27-02.
Abstract SY29-01: Deciphering oncogenic translation programs
Authors: Wendel Hans-Guido 
Published: July 2016

Abstract
New technologies provide precise measures of translation across the transcriptome. In particular, transcriptome-scale ribosome foot printing in conjunction with deep RNA sequencing developed by N. Ignolia and colleagues has shifted the focus in the field towards the output of mRNA translation. We can now measure differential mRNA translation programs and determine RNA sequence and structural features that guide translational responses to cellular and environmental cues. This has direct implications to cancer and beyond. It also extends our understanding of gene expression from transcriptional control to the regulation of protein production. We will provide examples of how these new approaches to studying mRNA translation are leading to new insight into cancer biology and therapy.
Citation Format: Hans-Guido Wendel. Deciphering oncogenic translation programs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY29-01.
Abstract SY38-03: Quantifying tumor heterogeneity in the microenvironment
Authors: Markowetz Florian 
Published: July 2016

Abstract
Cancer has long been understood as a somatic evolutionary process, but many details of tumor progression remain elusive. Here, I will talk about computational methods to infer evolutionary pathways leading to tumour heterogeneity.
Using a study in ovarian cancer I will describe how summary statistics of phylogenetic quantification of genetic heterogeneity can predict patient survival.
Then, I will present probabilistic frameworks to reconstruct intra-tumor evolution from data obtained by bulk bisulfite sequencing of mixed tumor samples or single cell genomes. Our approaches jointly estimates the number and composition of clones in the sample as well as the most likely tree connecting them.
I will finish with an outlook how to put cancer genomes in a tissue context by using image analysis and deconvolution of gene expression data.
Citation Format: Florian Markowetz. Quantifying tumor heterogeneity in the microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY38-03.
XRD investigation of the intercalation of nacrite with cesium chloride
Authors: Naamen S. , Jâafar N. , Ben Rhaiem H. , Ben Haj Amara A. , Plançon A. , Muller F. 
Published: July 2016

AbstractAn homogenous intercalated compound of dioctahedral 1:1 clay mineral with cesium chloride was prepared by immersing an homogeneous 8.4 Å hydrated nacrite in a CsCl-saturated solution. The nacrite/CsCl complex obtained was studied using X-ray diffraction and thermogravimetric analysis (TGA). The best agreement between the observed and the simulated ρ(z) (R = 7%) was obtained with one Cl− ion, one Cs+ ion and onewater molecule (per half-unit cell). The cation was located near the oxygen atom plane, while the anion was located near the hydroxyl groups of the adjacent layer. The number of the species intercalated in nacrite/CsCl was confirmed by TGA analysis. The best agreement between the calculated and the experimental hkl reflections, with h and/or k ≠ 0, corresponded to a stacking of 70% and 30% for T1 = −0.35a − 0.20b + 10.50n and T2 = +b/3 + 10.5n, respectively. These results indicate that the surface hydroxyls form hydrogen bonds with Cl− ions. The Cs+ ions are situated near the ditrigonal cavities of the tetrahedral sheet and they interact with the surface oxygen atoms whereas the H2O molecules interact with the intercalated species.
Efficient TALEN-mediated myostatin gene editing in goats
Authors: Yu Baoli , Lu Rui , Yuan Yuguo , Zhang Ting , Song Shaozheng , Qi Zhengqiang , Shao Bin , Zhu Mengmin , Mi Fei , Cheng Yong 
Published: July 2016

Abstract
Background
Myostatin (MSTN) encodes a negative regulator of skeletal muscle mass that might have applications for promoting muscle growth in livestock. In this study, we aimed to test whether targeted MSTN editing, mediated by transcription activator-like effector nucleases (TALENs), is a viable approach to create myostatin-modified goats (Capra hircus).

Results
We obtained a pair of TALENs (MTAL-2) that could recognize and cut the targeted MSTN site in the goat genome. Fibroblasts from pedigreed goats were co-transfected with MTAL-2, and 272 monoclonal cell strains were confirmed to have mono- or bi-allelic mutations in MSTN. Ten cell strains with different genotypes were used as donor cells for somatic cell nuclear transfer, which produced three cloned kids (K179/MSTN−/−, K52-2/MSTN+/−, and K52-1/MSTN+/+).

Conclusions
The results suggested that the MTAL-2 could disrupt MSTN efficiently in the goat genome. The mutated somatic cells could be used to produce MSTN-site mutated goats without developmental disruption. Thus, TALENs is an effective method for accurate genome editing to produce site-modified goats.
The Problem of Multiple Criteria Selection of the Surface Mining Haul Trucks
Authors: Bodziony Przemysław , Kasztelewicz Zbigniew , Sawicki Piotr 
Published: July 2016

Abstract
Vehicle transport is a dominant type of technological processes in rock mines, and its profit ability is strictly dependent on overall cost of its exploitation, especially on diesel oil consumption. Thus, a rational design of transportation system based on haul trucks should result from thorough analysis of technical and economic issues, including both cost of purchase and its further exploitation, having a crucial impact on the cost of minerals extraction. Moreover, off-highway trucks should be selected with respect to all specific exploitation conditions and even the user’s preferences and experience.
In this paper a development of universal family of evaluation criteria as well as application of evaluation method for haul truck selection process for a specific exploitation conditions in surface mining have been carried out. The methodology presented in the paper is based on the principles of multiple criteria decision aiding (MCDA) using one of the ranking method, i.e. ELECTRE III. The applied methodology has been allowed for ranking of alternative solution (variants), on the considered set of haul trucks. The result of the research is a universal methodology, and it consequently may be applied in other surface mines with similar exploitation parametres.
Organic Rankine Cycle for Residual Heat to Power Conversion in Natural Gas Compressor Station. Part II: Plant Simulation and Optimisation Study
Authors: Chaczykowski Maciej 
Published: July 2016

Abstract
After having described the models for the organic Rankine cycle (ORC) equipment in the first part of this paper, this second part provides an example that demonstrates the performance of different ORC systems in the energy recovery application in a gas compressor station. The application shows certain specific characteristics, i.e. relatively large scale of the system, high exhaust gas temperature, low ambient temperature operation, and incorporation of an air-cooled condenser, as an effect of the localization in a compressor station plant. Screening of 17 organic fluids, mostly alkanes, was carried out and resulted in a selection of best performing fluids for each cycle configuration, among which benzene, acetone and heptane showed highest energy recovery potential in supercritical cycles, while benzene, toluene and cyclohexane in subcritical cycles. Calculation results indicate that a maximum of 10.4 MW of shaft power can be obtained from the exhaust gases of a 25 MW compressor driver by the use of benzene as a working fluid in the supercritical cycle with heat recuperation. In relation to the particular transmission system analysed in the study, it appears that the regenerative subcritical cycle with toluene as a working fluid presents the best thermodynamic characteristics, however, require some attention insofar as operational conditions are concerned.
Methane Recovery from Gaseous Mixtures Using Carbonaceous Adsorbents
Authors: Buczek Bronisław 
Published: July 2016

Abstract
Methane recovery from gaseous mixtures has both economical and ecological aspect. Methane from different waste gases like mine gases, nitrogenated natural gases and biogases can be treated as local source for production electric and heat energy. Also occurs the problem of atmosphere pollution with methane that shows over 20 times more harmful environmental effect in comparison to carbon dioxide. One of the ways utilisation such gases is enrichment of methane in the PSA technique, which requires appropriate adsorbents. Active carbons and carbon molecular sieve produced by industry and obtained in laboratory scale were examined as adsorbent for methane recuperation. Porous structure of adsorbents was investigated using densimetry measurements and adsorption of argon at 77.5K. On the basis of adsorption data, the Dubinin-Radushkevich equation parameters, micropore volume (Wo) and characteristics of energy adsorption (Eo) as well as area micropores (Smi) and BET area (SBET) were determined.
The usability of adsorbents in enrichment of the methane was evaluated in the test, which simulate the basic stages of PSA process: a) adsorbent degassing, b) pressure raise in column by feed gas, c) cocurrent desorption with analysis of out flowing gas. The composition of gas phase was accepted as the criterion of the suitability of adsorbent for methane separation from gaseous mixtures. The relationship between methane recovery from gas mixture and texture parameters of adsorbents was found.