bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B31: miRNAs regulated cancer metastasis in esophageal squamous cell carcinoma
Authors: Kano Masayuki , Matsubara Hisahiro , Masahiko Takahashi 
Published: December 2017

Abstract
MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs and negatively regulate gene expression through base pairing of 3' UTRs of the target genes. Over the past decade, much of important evidences have been obtained to clarify that miRNAs are unusual expressed in human malignancies and could act as OncomiRs or Tumor suppressive miRs.
Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers of the gastrointestinal tract. Especially, metastatic recurrences after esophagectomy for ESCC bears unfortunately prognosis and little exists for treatment strategy. Clarification of molecular indicators of the origin cellular deregulation in ESCC have been important objective for cancer research in ESCC.
Recently, increasing number of studies have demonstrated the involvement of miRNAs in cancer metastasis. Especially, many studies have shown that microRNAs could target genes playing a role in epithelia-mesenchymal-transition (EMT), a cellular transformation process that allows cancer cells to acquire motility and invasiveness. EMT is considered an essential step driving the early phase of cancer metastasis.
We search for miRNAs in ESCC using the miRNA expression signatures and gain-of-function analysis. It is revealed that 3 miRNAs (miR-145, miR-133a and miR-133b) inhibit cell proliferation and cell invasion. These miRNAs, which have conserved sequences in the 3' UTR of FSCN1, inhibited FSCN1 expression. The identification of tumor-suppressive miRNAs, miR-145, miR-133a and miR-133b, directly control oncogenic FSCN1 gene. These signal pathways of ESCC could provide new insights into potential mechanisms of ESCC carcinogenesis.
FSCN1 is actin bundling protein, which is concerned with cancer invadopodia ,which is the phenomenon regarding cancer cell invasion into surrounding tissue. We focused on MMP14 and examined the gene expression of MMP14 in ESCC tissues and patient survival. FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also
evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells. The relationship between the expressions of miR-133 and MMP14 is strongly negative correlation. miR-145 and miR-133 play a chief role in cancer invasion and metastasis, which control invadopodia associated proteins.
The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.
Citation Format: Masayuki Kano, Hisahiro Matsubara, Takahashi Masahiko. miRNAs regulated cancer metastasis in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr B31.
Abstract IA05: Massively parallel search for synthetic lethal vulnerabilities using CRISPRi and CRISPRa
Authors: Weissman Jonathan 
Published: December 2017

Abstract
While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of their function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90-99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ~1000-fold range. Using these rules, we construct and validate genome-scale CRISPRi and CRISPRa libraries that enable systematic analysis of gene function including both essential and nonessential as well as long noncoding RNAs. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways. We have now adpated this approach to allow the largescale analysis of double knockdowns. This enables the systematic search for synthetic lethal interactions that will inform the rational design of combination drug therapies.
Citation Format: Jonathan Weissman. Massively parallel search for synthetic lethal vulnerabilities using CRISPRi and CRISPRa [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA05.
Abstract IA08: Systematic interrogation of cancer dependencies
Authors: Hahn William C. 
Published: December 2017

Abstract
Although we now have a draft view of the genetic alterations that occur in human cancer, the number of mutations found at low frequency and the molecular heterogeneity of most cancers makes identifying genes that contribute to cancer phenotypes challenging. Determining the function of genes altered in cancer genomes is essential to develop new therapeutic approaches. To complement these genome characterization studies, we have used genome scale gain and loss of function approaches to identify genes required for cell survival and transformation. Specifically, we have performed systematic studies to interrogate rare alleles found altered in cancer genomes and used advances in synthetic gene synthesis to prospectively interrogate all possible alleles of known cancer genes. In parallel, we have performed both genome scale RNAi and CRISRP-Cas9 screens in more than 500 cell lines to identify differentially essential genes and the context that specifies gene dependency. This approach now permits us to identify and classify cancer dependencies.
These studies allow us to begin to define a global cancer dependencies map.
Citation Format: William C. Hahn. Systematic interrogation of cancer dependencies [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA08.
Abstract IA13: A novel KRAS specific vulnerability in the nutrient stress response
Authors: Sweet-Cordero Alejandro 
Published: December 2017

Abstract
Oncogenic KRAS has multiple effects on cellular functions. A relatively poorly understood role of oncogenic KRAS is in regulation of nutrient stress. As a strategy to identify new KRAS-specific tumor vulnerabilities, we sought to explore the role of oncogenic KRAS in mediating the response to nutrient stress. A key observation is that the gene expression signature of oncogenic KRAS is markedly different in standard tissue culture conditions compared to more physiologic levels of glutamine. Glutamine is a key nutrient for tumor cells that supports nucleotide and amino acid biosynthesis, replenishes TCA cycle intermediates and contributes to redox metabolism. We identified oncogenic KRAS as an important regulator of the response to glutamine deprivation in non-small cell lung cancer (NSCLC). A significant fraction of the gene expression signature mediated by KRAS in low glutamine is mediated by activation of ATF4. Activation of the ATF4 stress response pathway is dependent on PI3K and expression of NRF2 downstream of oncogenic KRAS in NSCLC. Through this mechanism, KRAS alters amino acid uptake and metabolism and sustains mTORC1 signaling during nutrient stress. We identified regulation of asparagine synthetase (ASNS) as a key effect of oncogenic KRAS signaling via ATF4 during glutamine deprivation. Preliminary data indicates that simultaneous blockade of PI3K and ASNS may be a useful therapeutic strategy in lung cancer. Our studies underscore an important role for KRAS in metabolism of NSCLC and identify a need for further studies that evaluate KRAS vulnerabilities under conditions of nutrient stress.
Citation Format: Alejandro Sweet-Cordero. A novel KRAS specific vulnerability in the nutrient stress response [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr IA13.
Abstract PR14: MEK inhibitors block growth of Ataxia Telangiectasia Mutated (ATM) mutant lung tumors
Authors: Cruz Ferran Fece de la , Smida Michal , Nijman Sebastian 
Published: December 2017

Abstract
Introduction: Lung cancer is the leading cause of cancer death worldwide. In the past decade, deep sequencing projects have shed light on the molecular drivers commonly found altered in NSCLC. As a result, the first molecularly targeted agents have been approved for the treatment of tumors presenting activating oncogenic events in EGFR or EML4/ALK. However, the translation into therapies for tumors presenting loss-of-function mutations has proven challenging and constitutes an unexplored and promising field.
In order to narrow the gap between cancer genomics and effective treatments for tumors harboring mutations in well-defined tumor suppressor genes (such as PTEN, BRG1 or ATM), we have developed a genetically tractable lung cancer cell model. Focusing on lung adenocarcinoma, we have engineered a panel of isogenic cell lines capturing the molecular heterogeneity found in patients. This panel has been screened against a collection of drugs, comprising classical chemotherapeutics and kinase inhibitors, providing a comprehensive evaluation for hundreds of gene-drug interactions.
Results: The screen confirmed known or highly expected interactions, proving the robustness of our approach. Among the unexpected and most relevant hits, we have found that ATM-deficient cells are exquisitely sensitive to drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Extensive validation in ATM mutant patient-derived lung cancer cell lines has confirmed the synthetic lethal interaction between ATM and MEK in vitro and in vivo.
Mechanistically, the interaction may not be directly associated with the major role of ATM in DNA damage signaling. Rather, we have observed a deregulation of the crosstalk between the MAPK and AKT/mTOR signaling pathways as a consequence of ATM deficiency, resulting in an increased dependency on MEK kinase activity for cell survival.
Perspectives: Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma (5- 10%) but directly targeting these with drugs remains challenging. MEK inhibitors are currently being tested in clinical trials for efficacy in KRAS or BRAF mutant lung cancer. However, these mutations alone do not adequately predict response to MEK inhibition. Our findings indicate that including ATM mutation status in lung cancer as a mechanistic biomarker for MEK inhibitors can improve patient stratification. Ultimately, extending the applicability of these drugs beyond KRAS or BRAF mutant tumors.
Citation Format: Ferran Fece de la Cruz, Michal Smida, Sebastian Nijman. MEK inhibitors block growth of Ataxia Telangiectasia Mutated (ATM) mutant lung tumors [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr PR14.
Abstract PR15: Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma
Authors: Thompson Jordan M. , Nguyen Quy H. , Singh Manpreet , Pavesic Matthew W. , Nesterenko Irina , Nelson Luke J. , Liao Alicia , Razorenova Olga V. 
Published: December 2017

Abstract
Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, three other ROCK inhibitors, RKI 1447, GSK 429286, AT13148 selectively targeted VHL-deficient CC-RCC. Importantly, we found that mammalian target of rapamycin (mTOR) inhibitor Everolimus synergized with ROCK inhibitor RKI 1447 in targeting VHL-deficient cells. Accordingly, AT13148, an AGC kinase inhibitor blocking S6 kinase (S6K, downstream target of mTOR) in addition to ROCK1&2, showed the most strong synthetic lethality effect out of all ROCK inhibitors tested. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) β in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O2). These results suggest that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC.
Citation Format: Jordan M. Thompson, Quy H. Nguyen, Manpreet Singh, Matthew W. Pavesic, Irina Nesterenko, Luke J. Nelson, Alicia Liao, Olga V. Razorenova. Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr PR15.
Gender, Catholicism, and Communism in 1950s Shanghai (1950年代上海的性别、天主教与共产主义)
Authors: Mariani Paul P. 
Published: December 2017

In the 1950s, Shanghai witnessed a conflict between the Chinese Communist Party (ccp) and the Shanghai Catholic community. The ccp wanted this community to break ties with the pope and form an “independent” Catholic Church that would fall under the authority of the Chinese government. Many Catholics in Shanghai soon resisted what they perceived to be the unjust religious policies of the ccp. One of the “backbone elements” of Catholic resistance in Shanghai was young women. This study investigates how three young Catholic women dealt with the ccp’s encroaching religious policies. All three came from similar backgrounds and they all initially formed part of the Catholic resistance to ccp religious policies during the early 1950s. Afterward their trajectories differed dramatically due to the particular way in which the Communist revolution intervened in the life of each woman. This study thus illuminates the contested area of religious faith, state power, and gender in the early years of the People’s Republic of China.
上世纪五十年代，上海见证了中共与上海天主教会之间的冲突。中共命令上海天主教会断绝与教宗的联系，成为一个听命于中国政府的“独立”教会。上海的许多天主教徒很快就起来抵制这些他们视为不公正的宗教政策。反抗运动中的许多“骨干分子”是年轻女信徒。本文探究了三位年轻的女天主教信徒如何应对当时中共侵权的宗教政策。她们有相似的生活背景，并都在50年代初期参与了抵制中共宗教政策的运动。但是因为中共革命介入她们生命的不同方式，她们之后的人生轨迹大相径庭。这项研究因此阐述了在中华人民共和国初期，宗教信仰、国家政权与性别之间充满张力的互动。
On the Reduced North Atlantic Storminess during the Last Glacial Period: The Role of Topography in Shaping Synoptic Eddies
Authors: Rivière Gwendal , Berthou Ségolène , Lapeyre Guillaume , Kageyama Masa 
Published: December 2017

AbstractThe North Atlantic storminess of Last Glacial Maximum (LGM) fully coupled climate simulations is generally less intense than that of their preindustrial (PI) counterparts, despite having stronger baroclinicity. An explanation for this counterintuitive result is presented by comparing two simulations of the IPSL full climate model forced by Paleoclimate Modelling Intercomparison Project Phase 3 (PMIP3) LGM and PI conditions. Two additional numerical experiments using a simplified dry general circulation model forced by idealized topography and a relaxation in temperature provide guidance for the dynamical interpretation. The forced experiment with idealized Rockies and an idealized Laurentide Ice Sheet has a less intense North Atlantic storm-track activity than the forced experiment with idealized Rockies only, despite similar baroclinicity. Both the climate and idealized runs satisfy or support the following statements. The reduced storm-track intensity can be explained by a reduced baroclinic conversion, which itself comes from a loss in eddy efficiency to tap the available potential energy as shown by energetic budgets. The eddy heat fluxes are northeastward oriented in the western Atlantic in LGM and are less well aligned with the mean temperature gradient than in PI. The southern slope of the Laurentide Ice Sheet topography forces the eddy geopotential isolines to be zonally oriented at low levels in its proximity. This distorts the tubes of constant eddy geopotential in such a way that they tilt northwestward with height during baroclinic growth in LGM while they are more optimally westward tilted in PI.
Qualidade da Água Consumida em Escolas Estaduais do Municipio de Vitória da Conquista – BA
Authors: Menezes Patrícia De Oliveira , Fogaça Larissa Costa Silva 
Published: December 2017

A água é um recurso imprescindível no desenvolvimento de diversas atividades humanas. Apesar de ser uma fonte abundante em nosso planeta, apenas uma pequena parcela é própria para consumo, expondo os indivíduos a inúmeras doenças relacionadas a sua contaminação. Dessa forma objetivou-se com este estudo avaliar os parâmetros físico-químicos e microbiológicos para a caracterização da potabilidade das águas disponíveis nos bebedouros de escolas públicas no município de Vitória da Conquista, Bahia, de acordo com a Portaria n0 2914 de 12/12/2011 do Ministério da Saúde, utilizando o pHmetro, para a análise do potencial Hidrogeniônico (pH), o Condutivímetro microprocessado Químis para a análise de sólidos totais dissolvidos (TDS) e condutividade e o Aquatest Coli® (Laborclin), para realizar as análises de Coliformes totais e Escherichia coli. As amostras analisadas neste estudo atenderam aos limites dos parâmetros físico-químicos especificados pela Portaria n0 2914 de 12/12/2011 do Ministério da Saúde. Os resultados demonstraram ausência de coliformes totais e de Escherichia coli em todas as amostras analisadas, estando apropriadas para o consumo.
Activated carbon fiber from liquefied wood and polyvinyl butyral as an additive for production of flexible all-carbon yarn supercapacitors
Authors: Huang Yuxiang , Yu Wenji , Zhao Guangjie 
Published: December 2017

AbstractA novel way to prepare mesoporous activated carbon fibers (ACFs-P) has been developed, while the ACFs-P with high surface area were obtained from liquefied wood by combining polyvinyl butyral (PVB) blending and steam activation. The porosity properties of the new material was investigated by N2adsorption and the Brunauer–Emmett–Teller (BET) surface area was found to be 2710 m2g−1and a pore volume of 1.540 cm3g−1, of which 58.2% was mesoporous with diameters between 3 and 6 nm. ACFs-P had a higher methylene blue (MB) adsorption capacity (962 mg/g) than the PVB-added carbon fibers (CFs-P) and ACFs-P without PVB (ACFs-C). Flexible all-carbon yarn supercapacitors can be produced from ACFs-P as powder or fiber. The fiber approach led to yarn supercapacitors with a less favorable electrochemical performance than the powder based production owing to the poor strength of the fibers. A 10 cm long yarn supercapacitor from the powdered ACFs exhibited a high specific length capacitance of 43 mF cm−1at 2 mV s−1. Yarn supercapacitors showed an excellent mechanical flexibility and its capacitor properties were not diminished after bending or crumpling.
Bond performance of basalt fiber-reinforced polymer bars in conventional Portland cement concrete: a relative comparison with steel rebar using the hinged beam approach
Authors: Seis Muhammet , Beycioğlu Ahmet 
Published: December 2017

Abstract
This paper reports the results of an experimental investigation carried out to evaluate the bond stress behavior of basalt fiber-reinforced polymer (BFRP) bar and steel rebar (SR) in conventional C30-type concrete. The experimental program was conducted on testing 16 hinged beam specimens that were prepared according to BS 4449:2005+A2:2009 standard. Conventional C30-type concrete was used to produce hinged beams. In beam tests, bar diameter and embedment length were used as experimental variables. The bond performances of BFRP bar and SR were compared with the help of the load-slip results of hinged beam bending tests conducted on produced beam samples after 28 days of curing. Results showed that much higher bond stress values were obtained from BFRP bars compared to SR for both 12 and 8 mm bar diameters. Besides, the maximum bond stress values decreased with increasing bar diameter and embedment length for both BFRP bar and SR.