bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A41: Development of a risk analysis model for triple-negative breast cancer stages and treatment of African American women
Authors: Chowdhury Rupak , Nandy Shami , Tameru Berhanu
Published: January 2017

The main object of this study is to assess how different stages of triple-negative breast cancer (TNBC) influences treatment of triple negative breast cancer patient. The data was gathered from Alabama Department of Public Health. We developed a probabilistic pathway scenario tree based on the knowledge from the comprehensive literature review and organized the variables into twelve major parameter categories. We performed Monte Carlo simulations with the software @Risk 5.7 (Palisade Corporation) for the quantitative risk assessment to capture the uncertainty for the treatment of triple negative breast cancer and different stages of TNBC. The likelihood (LH) of having one of the treatments for Stage IV TNBC, Surgery and or Chemotherapy (CT) or none gave that the person is (African American women) AAW older than 50, TNBC ranges from a min. of 1.62 × 10−3 to a max. of 2.35 × 10−2 with the mean and standard deviation of 8.28 × 10−3 and 3.141 × 10−3 respectively. The LH of having one of the treatments for stage 1&2 of triple negative breast cancer, Surgery and or CT or none gave that the person is AAW older than 50, TNBC ranges from 1.78 × 10−5 to 1.053 × 10−1 with the mean and standard deviation of 2.74 × 10−2 and 2.06 × 10−2 respectively. However, there are no standard guidelines for Triple negative breast cancer patients, our study suggests that stage 1&2 triple negative breast cancer patients are most likely to be treated with either chemotherapy or surgery and stage 3, 4 triple negative breast cancer patient are most likely to be treated with combined surgery and chemotherapy.

Note: This abstract was not presented at the conference.

Citation Format: Rupak Chowdhury, Shami Nandy, Berhanu Tameru. Development of a risk analysis model for triple-negative breast cancer stages and treatment of African American women. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A41.
Abstract B18: Development of human STING agonists for prostate cancer immunotherapy
Authors: Wu Jian Hui
Published: January 2017

Recent studies have identified the host STING pathway as a critical mechanism of innate immune sensing of cancer, that drives type-I interferons (IFNs) production and promotes aggressive antitumor responses. Thus, STING agonists could be candidates for testing as stimulants for anticancer immune activity. Although DMXAA binds and activates mouse STING, it cannot activate human STING (hSTING). This species specificity is thought to be the reason that DMXAA showed dramatic effect against solid tumor in rodent models, but failed in human clinical trials. In this project, we aim to identify novel chemical compounds as agonists of hSTING.

By combining in silico screening and in vitro assays, we have discovered two novel chemical compounds that activate hSTING. Direct binding of our compounds with hSTING was confirmed by Surface plasmon resonance (SPR) analysis. We demonstrated that our hSTING agonist activated interferon signaling pathway in monocytic human THP-1 cells, which express endogenous hSTING. Further, our compound itself is not cytotoxic to 22Rv1 prostate cancer cells, but the spent supernatants of the THP-1 cells exposed to our compound are cytotoxic to 22Rv1 cells. Chemical optimization of initial active compounds is in progress. We aim to generate compound candidates as potent hSTING agonists for in vivo evaluation in rodent models.

Note: This abstract was not presented at the conference.

Citation Format: Jian Hui Wu. Development of human STING agonists for prostate cancer immunotherapy. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B18.
Abstract B30: Inhibition of eIF4E/MNK axis by novel MNKDAs reduces breast cancer tumor growth, migration, invasion and metastasis
Authors: Ramalingam Senthilmurugan , Gediya Lalji , Ramamurthy Vidya , Choi Yong , Lapidus Rena , Vincent Njar
Published: January 2017

Triple-negative breast cancer (TNBC) represents a molecularly heterogeneous subgrouping of high-risk breast tumors characterized by aggressive behavior, poor prognosis and lack of targeted therapeutic options. The translation initiation factor eIF4E, an oncogene essential for cap-dependent translation of specific mRNAs critical for cell division, cell survival, angiogenesis, and metastasis is commonly overexpressed in primary breast cancers including TNBC. eIF4E therapeutic targeting is considered novel and significant because tumor cells specifically overexpress eIF4E and develop an oncogene addiction to eIF4E, rendering the cells vulnerable to eIF4E inhibition, whereas normal cells are relatively insensitive. Phosphorylation of eIF4E at serine-209 is critical for the oncogenic activity of eIF4E, and it has been suggested that chemical compounds that prevent the phosphorylation of eIF4E could act as effective anticancer drugs. Herein, we report that a novel inhibitor of peIF4E function (Novel Retinamides, NRs), safely and potently suppresses breast tumor formation. Administration of novel retinamides (mnk degrading agents: MNKDAs) blocked the growth of primary breast tumors in MDA-MB-231 xenograft model, TNBC patient derived xenografts (PDX), and reduced the development of lung metastases in an invasive model. Mechanistically, NRs resulted in the degradation of MNKs (MNK1 and MNK2), a key kinase chiefly responsible for phosphorylating and activating eIF4E. This in turn hampered peIF4E involved translation initiation and activation of genes associated with cell proliferation and survival. Furthermore, MNK degradation by NRs also suppressed epithelial-to-mesenchymal transition, a process crucial for metastasis as evident by increased expression of E-cadherin and reduced expression of N-cadherin, fibronectin and vimentin; snail, slug, twist, fibronectin, claudin, lamin, TCF/ZEB-1, beta catenin, MMPs and vimentin. Taken together, the preclinical evidence of tumor regression and metastasis in TNBC models suggest that NRs offers considerable promise as new therapeutic candidate to target TNBC and metastatic breast cancer.

Citation Format: Senthilmurugan Ramalingam, Lalji Gediya, Vidya Ramamurthy, Yong Choi, Rena Lapidus, Njar Vincent. Inhibition of eIF4E/MNK axis by novel MNKDAs reduces breast cancer tumor growth, migration, invasion and metastasis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B30.
Abstract B33: Persistent activation of ERK and SMAD4 nuclear retention by high free fatty acids promote breast cancer metastasis
Authors: Wu Yong , Yu Xiaoting , Bhat Kruttika , Dwabe Sami , Atefi Mohammad , Vadgama Jay
Published: January 2017

Obesity increases the risk of developing distant metastatic recurrence, and diminishes overall and breast cancer-specific survival; however, the mechanisms behind this correlation and relevant therapeutic targets are poorly defined. Plasma free fatty acids (FFA) levels are usually elevated in obese individuals. Here, using human breast cancer cell lines, we found that TGF-β transiently activates the extracellular signal-regulated kinase (ERK) and subsequently marks SMAD4 for phosphorylation, which facilitates SMAD4-ubiquitin specific peptidase 9, X-linked (USP9x) interaction, SMAD4 nuclear retention, SMAD3-SMAD4 complex nuclear accumulation, and stimulated TGF-β/SMAD3–mediated transcriptional activity of Twist and Snail. USP9x competitively inhibited the E3 ubiquitin-protein ligase transcriptional intermediary factor 1 γ (TIF1γ) from binding and monoubiquitinating SMAD4. This process maintained SMAD4 nuclear retention and stabilized the SMAD3/SMAD4 complex in the nucleus. Inhibition of ERK resulted in SMAD4 de-phosphorylation, USP9x-SMAD4 disassociation and SMAD4-TIF1γ interaction, which ultimately marks SMAD4 for mono-ubiquitination, leading to SMAD4 nuclear export and termination of the transcription of Twist and Snail. In addition, loss of USP9x abolished TGF-β–induced SMAD4 nuclear retention and SMAD3/SMAD4 formation, leading to inhibition of Twist and Snail expression. We also found that ERK-induced SMAD4 T277 phosphorylation and SMAD4-USP9x interaction was required for TGF-β–induced breast cancer invasion, which was attributed to SMAD3/SMAD4-dependent up-regulation of the transcription factors, Twist and Snail. Importantly, FFA further facilitates TGF-β–induced ERK activation, SMAD4 phosphorylation, SMAD4 nuclear retention and SMAD3/SMAD4 formation, thus promoting TGF-β–dependent cancer progression. Inhibition of ERK and USP9x suppressed obesity-induced metastasis. Additionally, phospho-ERK and -SMAD4 levels correlated with activated TGF-β signaling and metastasis in obese patient breast cancer specimens. Altogether, we demonstrated that USP9x promotes breast cancer invasion by promoting nuclear retention of SMAD4 and identified crosstalk between USP9x and TGF-β/ERK/SMAD4/SMAD3 pathways. Our study highlights the vital interaction of USP9x and SMAD4 for governing TGF-β signaling and dyslipidemia-induced aberrant TGF-β activation during breast cancer metastasis.

Citation Format: Yong Wu, Xiaoting Yu, Kruttika Bhat, Sami Dwabe, Mohammad Atefi, Jay Vadgama. Persistent activation of ERK and SMAD4 nuclear retention by high free fatty acids promote breast cancer metastasis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B33.
Abstract B41: Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors
Authors: Single Andrew , Chen Augustine , Telford Bryony , Beetham Henry , Guilford Parry
Published: January 2017

E-cadherin (CDH1) is a cell-cell adhesion protein implicated in the epithelial-mesenchymal transition and frequently dysregulated in diffuse gastric cancer (DGC) and invasive lobular breast cancer (ILBC). Germline CDH1 mutations define hereditary diffuse gastric cancer (HDGC), a rare cancer syndrome characterised by highly penetrant DGC and an elevated rate of ILBC in females. There is a strong need to develop specific chemopreventative strategies for CDH1 germline mutation carriers which are capable of reducing the viability of early stage CDH1-deficient cancers whilst minimizing side effects.

We have previously applied a synthetic lethal approach to an isogenic pair of MCF10A breast cell lines, one with and one without functional CDH1 expression (MCF10A CDH1-/-), to screen for drugs which preferentially reduce the viability of CDH1-deficient cells. This led to our finding that histone deacetylase inhibitors (HDACi; entinostat and vorinostat) and SRC inhibitors (SRCi; saracatinib) are involved in synthetic lethal interactions with MCF10A CDH1-/- cells. Single agent therapy, however, only produces a modest synthetic lethal effect, leading to our interest in developing synergistic drug combinations.

We have now shown that statins, inhibitors of the HMG-CoA reductase enzyme, also show a synthetic lethal phenotype in the MCF10A isogenic cell line pair. This result suggests that survival of E-cadherin-deficient cells may be enhanced by the mevalonate pathway, a metabolic pathway responsible for synthesizing prenyl groups and subsequently activating the small GTPase proteins Rho, Rac, and Cdc42. SRC is also a known activator of GTPase proteins and combined statin and saracatinib treatment caused an enhanced reduction in cell viability in the isogenic MCF10A cells whilst maintaining the synthetic lethal phenotype. This drug combination was shown to be synergistic in both cell lines using the Chou-Talalay median effect analysis and is the first known example of synergy between a statin and SRC inhibitor. Combined statin and HDACi treatment also enhanced cell viability inhibition and was synthetic lethal in the MCF10A pair. This effect was observed using both class-I specific (entinostat) and pan- (vorinostat) HDACi and was synergistic in both cell lines using median effect analysis. These are the first known examples of synergistic drug combinations being used in the field of synthetic lethality and serve as a foundation for novel DGC and ILBC treatment options.

Citation Format: Andrew Single, Augustine Chen, Bryony Telford, Henry Beetham, Parry Guilford. Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B41.
Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection for Non-Ampullary Superficial Duodenal Tumor
Authors: Hoteya Shu , Furuhata Tsukasa , Takahito Toba , Fukuma Yumiko , Suzuki Yugo , Kikuchi Daisuke , Mitani Toshifumi , Matsui Akira , Yamashita Satoshi , Nomura Kosuke , Kuribayashi Yasutaka , Iizuka Toshiro , Kaise Mitsuru
Published: January 2017

Background: Endoscopic submucosal resection (ESD) and endoscopic mucosal resection (EMR) are well established as curable and safety procedures for treating superficial tumors of the stomach, esophagus and colon. However, a majority of endoscopic resection strategies for non-ampullary superficial duodenal tumors (NASDTs) remains undefined. The aim of this study was to clarify which was the right method for NASDT treatment - EMR or ESD. Summary: We analyzed 129 consecutive endoscopic resection (74 ESD and 55 EMR) procedures performed with NADSTs and divided the ESD group into 49 large ESD groups (more than 20 mm in diameter) and 25 small ESD groups (less than 20 mm in diameter). With respect to the technical outcomes of EMR/ESD for small size NASDTs, EMR was safer than ESD, but its nature of curability was inferior to that of ESD. The rates of complication such as perforation or delayed bleeding were significantly higher in both ESD groups than in the EMR group. However, the prophylactic endoscopic closure of large mucosal defects after ESD was useful for resolving those complications. The limitations of our study were involvement of a single-center, limited sample size, short follow-up duration and the retrospective design, which may have introduced selection bias. However, the present findings suggest that adequate endoscopic treatment strategy for NASDTs can lead to favorable outcomes and an excellent prognosis. Key Message: It is necessary to select EMR or ESD adequately for R0 resection of small NASDTs, according to their size and location. For large NASDTs, duodenal ESD with essential management is feasible and useful as a therapeutic procedure.
Rationale for the Evaluation of Renal Functional Reserve in Living Kidney Donors and Recipients: A Pilot Study
Authors: Spinelli Alessandra , Sharma Aashish , Villa Gianluca , Samoni Sara , Ramponi Francesco , Brocca Alessandra , Brendolan Alessandra , Chiaramonte Stefano , Castellano Giuseppe , Gesualdo Loreto , Ronco Claudio
Published: January 2017

Background: In living kidney transplantation, preoperative donors' renal functional reserve (RFR) may correlate with postoperative residual renal function in both donors and recipients. The aim of this study was to evaluate the donors' RFR before transplantation and to compare basal and stress renal function before and after transplantation in both donors and recipients. Methods: Seven pairs of living kidney donors and recipients were considered for this observational study. RFR was measured with a renal stress test (RST) before and after the kidney transplantation through an oral protein loading test (1 g/kg of body weight). RFR was defined as the difference between the maximum value of creatinine clearance after protein load (stress glomerular filtration rate, sGFR) and baseline creatinine clearance (basal GFR, bGFR). Results: Before transplantation, a significant difference between sGFR and bGFR (p = 0.04) was observed in donors, with an RFR = 30.6 (11.9-41.5) mL/min/1.73 m2. After kidney transplantation, sGFR was similar to bGFR for both donors and recipients (p = 0.13), with a limited RFR (7.9 [6.70-19.25] and 14.90 [-6.67 to 25.53] mL/min/1.73 m2, respectively). The sum of the donor's and recipient's post-transplant sGFR was similar to the pre-transplant donor's sGFR (p = 0.73). Conclusion: RST is a safe, feasible, easy, and an inexpensive tool that is able to quantify RFR. In living kidney transplantation, it can be used in clinical practice to measure the original global filtration capacity of the donor's kidneys (sGFR) and to quantify the susceptibility of donors and recipients in developing postoperative kidney dysfunction. However, further studies with an adequate sample size and follow-up period are needed to test this hypothesis.
Uma análise dos rendimentos do trabalho entre indivíduos com ensino superior no Brasil
Authors: Reis Maurício Cortez , Machado Danielle Carusi
Published: January 2017

Este artigo tem como objetivo analisar o mercado de trabalho para indivíduos que concluíram o ensino superior no Brasil, usando dados do Censo de 2010. A desigualdade de rendimentos entre os trabalhadores brasileiros de nível superior é extremamente elevada. De acordo com os resultados encontrados, um dos fatores que contribui para isso é a acentuada disparidade nos rendimentos do trabalho entre as áreas de formação profissional. Além disso, uma parcela dos trabalhadores com nível superior no Brasil atua em ocupações sem relação com a área de formação, o que tem como consequência uma penalidade nos rendimentos. Os resultados mostram também que a influência desses fatores varia substancialmente ao longo da distribuição de rendimentos do trabalho e pelo sexo do trabalhador
Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity
Authors: Nakao Kazuhiro , Kuwahara Koichiro , Nishikimi Toshio , Nakagawa Yasuaki , Kinoshita Hideyuki , Minami Takeya , Kuwabara Yoshihiro , Yamada Chinatsu , Yamada Yuko , Tokudome Takeshi , Nagai-Okatani Chiaki , Minamino Naoto , Nakao Yoko M. , Yasuno Shinji , Ueshima Kenji , Sone Masakatsu , Kimura Takeshi , Kangawa Kenji , Nakao Kazuwa
Published: January 2017

We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell–specific CNP knockout and vascular smooth muscle cell–specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell–specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell–specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell–specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell–specific GC-B knockout mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from vascular smooth muscle cell–specific GC-B knockout mice. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B.
Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia
Authors: Jia Yuanhui , Li Ting , Huang Xiaojie , Xu Xianghong , Zhou Xinyao , Jia Linyan , Zhu Jingping , Xie Dandan , Wang Kai , Zhou Qian , Jin Liping , Zhang Jiqin , Duan Tao
Published: January 2017

Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia. Our results show that the expression and localization of DNMT3A are dysregulated in preeclamptic placenta. Moreover, knockdown of DNMT3A obviously inhibits trophoblast cell migration and invasion. Mechanistically, IGFBP5 (insulin-like growth factor–binding protein 5), known as a suppressor, is upregulated by decreased DNMT3A because of promoter hypomethylation. Importantly, IGFBP5 downregulation can rescue the defects caused by DNMT3A knockdown, thereby, consolidating the significance of IGFBP5 in the downstream of DNMT3A in trophoblast. Furthermore, we detected low promoter methylation and high protein expression of IGFBP5 in the clinical samples of preeclamptic placenta. Collectively, our study suggests that dysregulation of DNMT3A and IGFBP5 is relevant to preeclampsia. Thus, we propose that DNMT3A and IGFBP5 can serve as potential markers and targets for the clinical diagnosis and therapy of preeclampsia.
A new subspecies, Eumeces schneiderii barani n. ssp (Reptilia: Sauria: Scincidae) from Turkey
Authors: KUMLUTAS YUSUF , ARIKAN HÜSEYIN , ILGAZ ÇETIN , KASKA YAKUP
Published: January 2017

This study describes a new subspecies of lizard, Eumeces schneiderii barani n. ssp., from western Anatolia, Turkey. The new subspecies is differentiated from other two subspecies in Anatolia (E. s. princeps and E. s. pavimentatus) by its characteristic colour and colour-pattern as well as by the scales along the dorsal midline. Results obtained from polyacrylamide gel disc electrophoresis support this differentiation.
Aphis species (Hemiptera, Aphididae) living on Mulinum (Apiaceae) in South America, with a description of a new species
Authors: RODRÍGUEZ SANDRA GONZÁLEZ , BROWN PAUL A. , ORTEGO JAIME , CIRUELOS SARA I. LÓPEZ , NAFRÍA JUAN M. NIETO
Published: January 2017

Aphis species living on the South American native genus Mulinum are studied. Aphis vurilocensis Nieto Nafría, Brown and López Ciruelos, sp. n. is described from apterous viviparous females. Alate viviparous females, oviparous females and winged males of Aphis roberti are described. Knowledge of intraspecific variability of apterous viviparous females of A. martinezi, A. paravanoi and A. roberti is developed. An identification key of apterous viviparous females of Aphis species living on Mulinum is presented.
Revision of the genus Kailasha (Lepidoptera, Erebidae, Arctiinae) from Oriental region, with description of one new species
Authors: ULZIIJARGAL BAYARSAIKHAN , NA SOL-MOON , BAE YANG-SEOP
Published: January 2017

The genus Kailasha Singh & Kirti of Erebidae in Oriental Region is reviewed, with six species including a new species, Kailasha babensis Bae & Bayarsaikhan, sp. n., which is closely similar to effracta group in the superficial characters. Two species, K. pellucida (Rothschild), comb. n. and K. angkorensis Bayarsaikhan & Bae, comb. n., are newly combined from the genus Cyana Walker. Brief descriptions on all known species, with illustrations of adults and both sexes of genitalia are provided. A key to species is given.
SYNAMET - A Microcorpus of Synesthetic Metaphors. Preliminary Premises of the Description of Metaphor in Discourse
Authors: Zawisławska Magdalena Anna
Published: January 2017

SYNAMET - A Microcorpus of Synesthetic Metaphors. Preliminary Premises of the Description of Metaphor in DiscourseThis article describes the preliminary premises of metaphor annotation in SYNAMET - the developing microcorpus of synesthetic metaphors. The analysis is based on the CLST theory (Context-Limited Simulation Theory) put forward by D. Ritchie. According to this theory, the metaphor’s vehicle may activate various types of associations between words: semantic relations, perceptual sensations, or emotional simulations. The range of potential associations evoked by the vehicle is limited by the topic, i.e. the lexical context in which the metaphor appears. The relations between the vehicle and the topic may be presented in the form of a semantic frame.To reconstruct the frames within the project, linguistic works devoted to sensory perception- vision, hearing, smell and taste- will be utilized. The corpus annotation will consist of the following stages: 1) metaphor identification, 2) indication of the metaphor cluster (CM) - a phrase or a passage of the text, centered around one referent, 3) isolation of the metaphorical units (MU) - word forms or phrases combining lexemes primarily belonging to different perceptual frames.The outcome of the MU analysis will include: a general metaphorical scheme of the MU, lexical items activating the frame of the MU (together with their grammatical description), a detailed metaphor scheme of the MU, and the semantic and grammatical categorization of the MU. SYNAMET – mikrokorpus metafor synestezyjnych. Wstępne założenia opisu metafory w dyskursieArtykuł opisuje wstępne założenia anotacji metafor w powstającym mikrokorpusie metafor synestezyjnych SYNAMET. Podstawą metody opisu będzie teoria CLST (Context-Limited Simulation Theory) D. Ritchie’go. W myśl tej teorii nośnik metafory (vehicle) może aktywować różne typy powiązania między wyrazami: semantyczne, zmysłowe lub emocjonalne. Potencjalny zakres powiązań nośnika ogranicza topik (topic), czyli kontekst, w którym metafora się pojawia. Powiązania nośnika oraz topiku przedstawia się w postaci ram interpretacyjnych.W rekonstrukcji ram na potrzeby korpusu wykorzystane zostaną prace językoznawcze poświęcone percepcji zmysłowej: wzrokowi, słuchowi, zapachowi, smakowi. Anotacja korpusu będzie przebiegać według następującego schematu: 1) identyfikacja metafor, 2) wyodrębnienie w tekście układu metaforycznego (UM) – frazy lub fragmentu tekstu, zorganizowanego wokół jednego referenta, 3) wyodrębnienie jednostek metaforycznych (JM) – form wyrazowych lub fraz, w których występuje połączenie leksemów przynależnych prymarnie do różnych ram percepcyjnych.Wyniki analizy JM zostaną przestawione w postaci: ogólnego schematu metaforycznego, zestawu wyrazów aktywujących ramy (wraz z ich opisem gramatycznym), szczegółowego schematu metaforycznego, kategoryzacji semantycznej i gramatycznej metafor.
Technical Features of the Architecture of an Electronic Trilingual Dictionary
Authors: Chetverikov Grygorii , Vechirska Iryna , Puzik Oleksii
Published: January 2017

Technical Features of the Architecture of an Electronic Trilingual DictionaryThis article is devoted to the development of the software system used to create an English-Russian-Ukrainian terminological dictionary. Scanned and recognized documents in MSWord format were the input data for the dictionary. Issues which appeared during the parsing of the input data are analyzed and solutions using regular expressions are identified. This article also describes the scheme of the dictionary’s lexicographical database, and its classes of models, views and view models.In addition, a detailed description of the software system from a user’s perspective is included, the prospects for the usage of the dictionary are discussed, and the methods used during the development of the system are described.The software system is built using the design pattern Model-View-View-Model. Through the use of this pattern, internal logic is separated from user interface, thus changes made in different parts of the software may be independent. The developed software system allows users to edit, to fill, and thus to create new thematic transferable electronic dictionaries. The main advantage of the system is the equality of languages, i.e. each user can decide which language is to be major. Opracowanie oprogramowania trzyjęzycznego słownika elektronicznegoArtykuł jest poświęcony opracowaniu oprogramowania rosyjsko-ukraińsko-angielskiego słownika terminologicznego. Za wejściowe dane autorzy przyjęli zeskanowane i rozpoznane dokumenty w formacie MSWord. Błędy powstałe w czasie analizy składniowej wejściowych danych zostały przeanalizowane, a autorzy wskazali drogę ich likwidacji za pomocą regularnych wyrażeń.W pracy została dokładnie opisana baza leksykograficzna danych słownika, zostały opisane klasy modelu danych i klasy modelu prezentacji systemu. Oprogramowanie jest zbudowane w taki sposób, aby można było wykorzystać szablon projektowania Model-View-ViewModel. Dzięki wykorzystaniu tego szablonu interfejs użytkowania jest oddzielony od logiki programu, co pozwala wprowadzać niezależne zmiany poszczególnych części oprogramowania.Sporządzone oprogramowanie pozwala na redagowanie, uzupełnienie i tym samym tworzenie nowych tematycznych słowników przekładowych. Zaletą systemu jest równorzędność języków. Autorzy nakreślili zarówno sposoby wykorzystania samego słownika, jak i metody jego budowania.
Between Galileo and Darwin, or Towards a Unified Mode of Idealization in Cognitive Linguistics
Authors: Strugielska Ariadna
Published: January 2017

Between Galileo and Darwin, or Towards a Unified Mode of Idealization in Cognitive LinguisticsThe aim of this paper is to demonstrate that Cognitive Linguistics is in need of a coherent model through which the meaning of symbolic units can be represented. Departing from the premise that scientific theorizing requires taking a stance on the nature of idealization, the current discussion concentrates on cognitive linguists’ perspectives on the process, and reveals a lack of uniformity in the models proposed.On the whole, generalizations in Cognitive Linguistics are conducted in a manner reflecting the basic commitments of the approach, and hence the idealized models discussed strive to capture the embodied nature of cognition reflected in the semantic poles of symbolic units.However, a detailed analysis shows that a number of significant choices underlying the process of abstraction are random. Consequently, the modes of idealization revealed through semantic frames and cognitive domains lead to the emergence of barely compatible semantic categories which are assumed to represent the meaning of the same symbolic unit.It is thus postulated that if Cognitive Linguistics aspires to become a mature scientific theory, whose constructs and hypotheses can be operationalized and falsified, it needs to develop a more unified framework in which the situated and distributed natures of meaning are accounted for in a motivated manner. Między Galileuszeam a Aarwinem albo o spójnym modelu idealizacji w językoznawstwie kognitywnymCelem niniejszego artykułu jest wskazanie konieczności stworzenia spójnego modelu reprezentacji znaczeniowej jednostek symbolicznych w obrębie językoznawstwa kognitywnego. Przyjmując jako punkt wyjścia założenie, że podstawą budowania teorii naukowych jest idealizacja, dokonany zostaje przegląd modeli reprezentacji semantycznej, proponowanych przez czołowych językoznawców kognitywnych.Analiza wyidealizowanych modeli kognitywnych w ujęciu Fillmore’a (1985), Lakoffa (1987) i Langackera (1987) wskazuje na zbieżności na poziomie ogólnym, czyli na zgodność, iż biegun semantyczny jednostki symbolicznej winien odzwierciedlać ucieleśnioną naturę poznania. Na poziomie szczegółowym jednakże można zauważyć szereg rozbieżności między omawianymi modelami, wynikających z nieuzasadnionych wyborów badaczy dotyczących sposobu abstrahowania.W rezultacie wykazano, że znaczenie tej samej jednostki symbolicznej jest w językoznawstwie kognitywnym definiowane odmiennie, w zależności od przyjętej procedury idealizacji. Zaobserwowane niekonsekwencje metodologiczne podają w wątpliwość dojrzałość językoznawstwa kognitywnego jako teorii naukowej.
On the Dynamical Control of the Mesosphere–Lower Thermosphere by the Lower and Middle Atmosphere
Authors: Smith Anne K. , Pedatella Nicholas M. , Marsh Daniel R. , Matsuo Tomoko
Published: January 2017

The NCAR Whole Atmosphere Community Climate Model (WACCM) is used to investigate the dynamical influence of the lower and middle atmosphere on the upper mesosphere and lower thermosphere. In simulations using a methodology adapted from the “specified dynamics” (nudged) version of the model, horizontal winds and temperature over part of the vertical range of the atmosphere are relaxed toward results from a previous simulation that serves as the true simulation, equivalent to meteorological analysis. In the upper mesosphere, the magnitude of the divergence of the constrained simulations from the true simulation depends on the vertical extent and frequency of the data used for nudging the model and grows with altitude. The simulations quantify the error growth of the model dynamical fields when data and forcing terms are known exactly and there are no model biases. The error growth rate and the ultimate discrepancy between the nudged and true fields depend strongly on the method used for representing gravity wave drag. The largest error growth occurs when the gravity wave parameterization uses interactive wave sources that depend on convective activity or fronts. Errors are reduced when the same parameterization is used with smoothly varying specified wave sources. The smallest errors are seen when the parameterized gravity wave drag is replaced by linear Rayleigh friction damping on the wind speed. These comparisons demonstrate the role of gravity waves in transporting the variability of the troposphere into the mesosphere and lower thermosphere.
Cloud-Base Height Estimation from VIIRS. Part I: Operational Algorithm Validation against CloudSat
Authors: Seaman Curtis J. , Noh Yoo-Jeong , Miller Steven D. , Heidinger Andrew K. , Lindsey Daniel T.
Published: January 2017

The operational VIIRS cloud-base height (CBH) product from the Suomi–National Polar-Orbiting Partnership (SNPP) satellite is compared against observations of CBH from the cloud profiling radar (CPR) on board CloudSat. Because of the orbits of SNPP and CloudSat, these instruments provide nearly simultaneous observations of the same locations on Earth for a ~4.5-h period every 2–3 days. The methodology by which VIIRS and CloudSat observations are spatially and temporally matched is outlined. Based on four 1-month evaluation periods representing each season from June 2014 to April 2015, statistics related to the VIIRS CBH retrieval performance have been collected. Results indicate that when compared against CloudSat, the VIIRS CBH retrieval does not meet the error specifications set by the Joint Polar Satellite System (JPSS) program, with a root-mean-square error (RMSE) of 3.7 km for all clouds globally. More than half of all matching VIIRS pixels and CloudSat profiles have CBH errors exceeding the 2-km error requirement. Underscoring the significance of these statistics, it is shown that a simple estimate based on a constant cloud geometric thickness of 2 km outperforms the current operational CBH algorithm. It was found that the performance of the CBH product is impacted by the accuracy of upstream retrievals [primarily cloud-top height (CTH)] and the a priori information used by the CBH retrieval algorithm. However, even when CTH errors were small, CBH errors still exceed the JPSS program error specifications with an RMSE of 2.3 km.
A Gaussian Mixture Model Smoother for Continuous Nonlinear Stochastic Dynamical Systems: Applications
Authors: Lolla Tapovan , Lermusiaux Pierre F. J.
Published: January 2017

The nonlinear Gaussian Mixture Model Dynamically Orthogonal (GMM–DO) smoother for high-dimensional stochastic fields is exemplified and contrasted with other smoothers by applications to three dynamical systems, all of which admit far-from-Gaussian distributions. The capabilities of the smoother are first illustrated using a double-well stochastic diffusion experiment. Comparisons with the original and improved versions of the ensemble Kalman smoother explain the detailed mechanics of GMM–DO smoothing and show that its accuracy arises from the joint GMM distributions across successive observation times. Next, the smoother is validated using the advection of a passive stochastic tracer by a reversible shear flow. This example admits an exact smoothed solution, whose derivation is also provided. Results show that the GMM–DO smoother accurately captures the full smoothed distributions and not just the mean states. The final example showcases the smoother in more complex nonlinear fluid dynamics caused by a barotropic jet flowing through a sudden expansion and leading to variable jets and eddies. The accuracy of the GMM–DO smoother is compared to that of the Error Subspace Statistical Estimation smoother. It is shown that even when the dynamics result in only slightly multimodal joint distributions, Gaussian smoothing can lead to a severe loss of information. The three examples show that the backward inferences of the GMM–DO smoother are skillful and efficient. Accurate evaluation of Bayesian smoothers for nonlinear high-dimensional dynamical systems is challenging in itself. The present three examples—stochastic low dimension, reversible high dimension, and irreversible high dimension—provide complementary and effective benchmarks for such evaluation.
Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment
Authors: Shafat Manar S. , Oellerich Thomas , Mohr Sebastian , Robinson Stephen D. , Edwards Dylan R. , Marlein Christopher R. , Piddock Rachel E. , Fenech Matthew , Zaitseva Lyubov , Abdul-Aziz Amina , Turner Jeremy , Watkins Johnathan A. , Lawes Matthew , Bowles Kristian M. , Rushworth Stuart A.
Published: January 2017

Key Points

Bone marrow adipocytes support AML survival. AML induces adipocyte lipolysis of triglyceride to free fatty acids and subsequent transport by FABP4.
TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1
Authors: Jahn Lorenz , Hombrink Pleun , Hagedoorn Renate S. , Kester Michel G. D. , van der Steen Dirk M. , Rodriguez Tania , Pentcheva-Hoang Tsvetelina , de Ru Arnoud H. , Schoonakker Marjolein P. , Meeuwsen Miranda H. , Griffioen Marieke , van Veelen Peter A. , Falkenburg J. H. Frederik , Heemskerk Mirjam H. M.
Published: January 2017

Key Points

Isolation and characterization of a high-affinity TCR targeting the intracellular B cell–specific transcription factor BOB1. T cells expressing a BOB1-specific TCR lysed and eradicated primary multiple myeloma and other B-cell malignancies in vitro and in vivo.
Kaleidoscope
Authors: Tracy Derek K. , Joyce Dan W. , Shergill Sukhwinder S.
Published: January 2017

Tapping into your New Year resolutions, we present some cautionary data to consider.

Recent research on novel addiction types suggests that, in addition to hunger, the urge to eat is considerably influenced by environmental cues. Obese individuals have been shown to be more sensitive to these, with subsequent stronger craving and larger portion sizes. Neurobiologically, this has been linked with pathological alterations to cue-triggered motivational responses in the nucleus accumbens (NAc) parallel to those seen in drug addiction. Oginsky et al investigated the effects of a junk-food diet on obesity-susceptible and obesity-resistant rats. Glutamatergic calcium-permeable AMPA receptor (CP-AMPAR) functioning in the NAc showed more rapid and long-lasting (for weeks after cessation of junk-food consumption) increases in the obesity-sensitive group. CP-AMPARs mediate cue-triggered food seeking, and their changes in the brain occurred before weight gain. The data support the concept that ‘junk food addiction’ induced by the consumption of fatty and high-sugar foods may be contributing to the obesity epidemic.
Good Girls Revolt
Authors: Cunningham Maura Elizabeth
Published: January 2017

Given the limited right to assembly in China, a mass feminist movement that confronts the Communist Party is unlikely to materialize, argues historian Maura Elizabeth Cunningham. But fragmented and incremental pushes for women's rights will continue for years to come, and they will be no less revolutionary for being quiet.
The Great European Unraveling?
Authors: Polyakova Alina
Published: January 2017

After Britain voted to leave the EU, the European dream of a united continent is at risk but not dead. The Atlantic Council's Alina Polyakova argues that EU leaders must create opportunities for young people to reap the benefits of the economic bloc's accomplishments. Unless a new generation is made a political priority, it could be on the verge of being lost to the far-right populist parties sweeping across Europe.
The Newest Power Couple
Authors: Geranmayeh Ellie
Published: January 2017

Russia and Iran's military and economic ties are stronger than ever, according to Ellie Geranmayeh, a policy fellow at the European Council on Foreign Relations. Fueled by military cooperation in Syria, resistance to what they consider the U.S.' regime change agenda, and a shared vision of global order, the Iran-Russia relationship seems poised to shape the Middle East for years to come.
Editors’ Note
Authors: Bayrasli Elmira , Bohn Lauren
Published: January 2017

As long as institutions are male-dominated, society will continue to look to men as authorities, argue guest editors Elmira Bayrasli and Lauren Bohn, the co-founders of Foreign Policy Interrupted. The solutions to today's problems cannot be constructed in the minds of only half the population. To address the world's challenges, we must meaningfully change whom we call upon as experts. We must insist on a media landscape where more women are quoted, bylined, and miked.
Retouching Queer Kinship
Authors: Jacobs Karen
Published: January 2017

Annie Leibovitz's postmortem photograph of Susan Sontag in A Photographer's Life, 1990–2005 publicizes its subject in the same visual space that protects its privacy, writing over its contemporaneity with a series of more legible nineteenth-century and modernist visual codes, just as it aspires to write over celebrity spectacle with the intimate and sustained gaze of contemplation and witness. This process of writing over is not just spatial but temporal, anchored in moments of rupture, suture, and recursivity, as well as in strategies through which the apparently static image aspires to acknowledge, touch, and potentially rework its usable pasts. The volume's collective use of “temporal asynchrony” constitutes a queering of the latent teleologies of linear sequence (from the teleology of heterosexual reproduction to the inscription of ideas of social order broadly), and in terms requisite to Leibovitz's project to redescribe kinship as queer or lesbian history.
Queer History Queer Memory
Authors: Doan Laura
Published: January 2017

If we are serious about producing knowledge of the past in all its complexity—that is, as something we think that we know already as well as pastness in all its radical strangeness—it is vital to grasp the epistemological consequences in conceptualizing practices in oppositional terms, a tendency pervasive among historians and queer specialists alike. Using the case of Alan Turing to unpick this oppositional logic reveals the paralyzing effects of polarization but also, and perhaps more urgently, the paramount importance in forging any number of pathways in creating queer narratives of pastness, including the unmaking of history. Accounting for the messiness and complexity of our movements through the labyrinth of history and memory calls for recognizing the boundaries of praxis as delineated and mutable, conflicting and intertwined.
The Desert War of a Carolingian Monk
Authors: Dutton Paul Edward
Published: January 2017

How small can microhistorians go? The article proposes the advantages of “particle history,” the intense investigation of small, often isolated and dislocated fragments, and how they connect to the worlds to which they once belonged. To demonstrate the method, the article takes a single stand-alone sentence, a colophon, from an early ninth-century manuscript, Brussels, Bibliothèque Royale de Belgique 8216-8218, in which the scribe, one Ellenhart, reports that he copied the book while on a military campaign and supplies the dates of his copying. This evidence leads the author and readers on a journey to reconstruct a military campaign to Hunia (Hungary) in 819, the reasons for that military venture, the nature of the army's travel, and the scribe's role and progress in making his book. But why was Ellenhart there at all and what did he choose to copy while on campaign? To answer those questions the author examines the special character and critical tensions of Carolingian monasticism and why the monk chose the lives and sayings of the desert fathers to copy while on campaign. From a single sentence in an obscure manuscript, a world of associations and connections opens, reminding us that microhistory is not reductive, as is sometimes claimed, but expansive, for when it works it connects its objects of inquiry to wider worlds of meaning and importance.
A Microhistory of the Womb from the N-Town Mary Plays to Gorboduc
Authors: Petrosillo Sara
Published: January 2017

This essay examines representations of the womb across late medieval and early modern performance. The N-Town Mary plays and the Elizabethan tragedy Gorboduc are separated by less than a century but are rarely examined in light of one another. Using microhistorical methods and formal textual analysis, the essay zooms in on the trope of the womb across the theological divide separating these plays. It argues that these representations demonstrate a consistent and ambivalent connection between the mind and womb, a connection that does not subordinate one part of the body to another, but instead makes visible a dialectical relationship between the two. Examining literary representations of individual and social experiences of premodern pregnancy, the essay offers a complementary approach to historical archival methods.