bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B19: Targeting dependencies within apoptotic pathways through inhibition of BET bromodomains
Authors: Conery Andrew R. , Centore Richard C. , Spillane Kerry L. , Follmer Nicole E. , Bommi-Reddy Archana , Hatton Charlie , Bryant Barbara M. , Greninger Patricia , Amzallag Arnaud , Benes Cyril H. , Mertz Jennifer A. , Sims Robert J. 
Published: January 2017

Abstract
Cancer is driven in large part by dysregulated transcriptional programs that allow for the acquisition of the many ‘Hallmarks of Cancer.' Multiple regulatory factors are essential for the establishment and maintenance of these cancer-specific transcriptional programs, and this dependence creates vulnerabilities that can be therapeutically targeted. Here we describe a selective dependence on the bromodomain and extraterminal (BET) family of proteins for the reprogramming of apoptotic signaling networks and demonstrate how this dependence can be predicted prior to therapeutic intervention. We demonstrate in phenotypically sensitive cell lines that BET inhibition results in a rapid and robust transcriptional response among regulators of apoptosis, and that this transcriptional response is correlated with changes in the apoptotic threshold of target cells and subsequent apoptosis. We show that the robustness of the apoptotic response, and not that of the cytostatic response, predicts phenotypic sensitivity to BETi. Consistent with this, we observed that acquired BETi tolerance in two disparate cellular models is driven by dysregulated expression of anti-apoptotic BCL2 family proteins, and that genetic or pharmacological manipulation of apoptotic signaling can modify the phenotypic response to BETi. We further demonstrate that the basal expression levels of a set of apoptotic factors significantly predict preclinical response to BETi, and in particular note that BETi preferentially targets those cells that are dependent on BCL2 for survival. Our findings suggest that tumor cells have acquired a dependence on BET bromodomain function to evade apoptosis, and highlight opportunities to exploit this dependence in the clinic through rational patient selection and drug combination strategies.
Citation Format: Andrew R. Conery, Richard C. Centore, Kerry L. Spillane, Nicole E. Follmer, Archana Bommi-Reddy, Charlie Hatton, Barbara M. Bryant, Patricia Greninger, Arnaud Amzallag, Cyril H. Benes, Jennifer A. Mertz, Robert J. Sims, III. Targeting dependencies within apoptotic pathways through inhibition of BET bromodomains. [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 B19.
Abstract B23: Crucial deubiquitinases in cancer cell survival
Authors: Kategaya Lorna , Cuellar Trinna , Haley Ben , Liu Jinfeng , Tran Andy , Cao Yi , Stokoe David , McCleland Mark , Blackwood Beth , Yee Sharon , Drobnick Joy , Drummond Jake , Ernst James , Kwok Michael , Ly Cuong , Pastor Richard , Lello Paola Di , Ndubaku Chudi , Blake Robert , Tsui Vickie , Murray Jeremy , Maurer Till , Wertz Ingrid 
Published: January 2017

Abstract
Deubiquitinases (DUBs) are enzymes that proteolytically cleave ubiquitin from substrates. Substrates include oncogenes, tumor suppressors and polyubiquitinated proteins marked for degradation by the proteasome. Ubiquitin specific peptidase-7 (USP7) deubiquitinates MDM2 (an oncogene). MDM2 is a ligase that ubiquitinates p53 (a tumor suppressor protein), targeting it for proteosomal degradation. As such, USP7 is a promising cancer target because its inhibition stabilizes p53 and thereby promotes apoptosis and cell cycle arrest, processes that are often deregulated in tumors (Nicholson and Suresh Kumar, 2011). We found that USP7 was selectively druggable following a fragment-based lead discovery effort to obtain USP7 antagonists. Cellular and xenograft studies confirm that inhibiting USP7 activity stabilized p53 levels and p53-downstream target, p21. Additionally, normal primary and p53-null cells were less sensitive than the corresponding p53-WT cancer cells to USP7 inhibition.
To investigate whether other DUBs are involved in cancer cell survival, we carried out a drop-out CRISPR screen using a pooled DUB library in HCT116 and A549 cells. Out of the approximately 100 DUBs targeted, nine, including USP7, were found to affect cell viability. These hits were validated using siRNA-mediated knockdown in cancer cell lines (A549, HCT116, MCF7). Three DUBs that robustly decreased cell proliferation were further tested in normal cells (Human Mammary Epithelial Cells and Human Bronchial Epithelial Cells). DUB protein expression levels and activity were also determined. In general, DUB expression levels, activity and knockdown efficiency were higher in cancer cells compared to normal cells. Collectively, our studies support the hypothesis that USP7 inhibition may be an efficacious strategy to promote cancer cell death. Furthermore, there are other DUBs that should be considered as novel cancer targets.
Citation Format: Lorna Kategaya, Trinna Cuellar, Ben Haley, Jinfeng Liu, Andy Tran, Yi Cao, David Stokoe, Mark McCleland, Beth Blackwood, Sharon Yee, Joy Drobnick, Jake Drummond, James Ernst, Michael Kwok, Cuong Ly, Richard Pastor, Paola Di Lello, Chudi Ndubaku, Robert Blake, Vickie Tsui, Jeremy Murray, Till Maurer, Ingrid Wertz. Crucial deubiquitinases in cancer cell survival. [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 B23.
Myeloid-Derived Suppressor Cells
Authors: Gabrilovich Dmitry I. 
Published: January 2017

AbstractMyeloid cells developed evolutionarily as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master—tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC). These cells are closely related to neutrophils and monocytes. MDSCs are not present in the steady state of healthy individuals and appear in cancer and in pathologic conditions associated with chronic inflammation or stress. These cells have emerged as an important contributor to tumor progression. Ample evidence supports a key role for MDSCs in immune suppression in cancer, as well as their prominent role in tumor angiogenesis, drug resistance, and promotion of tumor metastases. MDSCs have a fascinating biology and are implicated in limiting the effects of cancer immunotherapy. Therefore, targeting these cells may represent an attractive therapeutic opportunity. Cancer Immunol Res; 5(1); 3–8. ©2016 AACR.
Efficacy and Safety of Coronary Sinus Aspiration During Coronary Angiography to Attenuate the Risk of Contrast-Induced Acute Kidney Injury in Predisposed Patients
Authors: Diab Osama Ali , Helmy Mostafa , Gomaa Yasser , El-Shalakany Reem 
Published: January 2017

Background—
The incidence of contrast-induced acute kidney injury is strongly related to the amount of the given contrast. Our objectives were to evaluate the efficacy and safety of coronary sinus aspiration (CSA) procedure to reduce the volume of the given contrast and attenuate the risk of contrast-induced acute kidney injury.

Methods and Results—

The study included 43 patients with type 2 diabetes mellitus and renal impairment (creatinine 1.5–3 mg/dL) who were candidates for coronary angiography. Eighteen patients were subjected to CSA procedure during coronary angiography (CSA group), and 25 patients served as a control group. Periprocedural standard care was given. In CSA group, the coronary sinus was cannulated via subclavian or femoral venous approaches, and aspiration was done directly from a transseptal sheath (8 patients) or through a balloon occlusion catheter placed through the sheath (10 patients) simultaneously during each coronary injection. Estimated volume of aspirated contrast was calculated based on the percentage reduction in hematocrit value of the aspirate in relation to the patient’s baseline hematocrit. Fraction of aspirated contrast was calculated by dividing estimated volume of aspirated contrast over the volume of injected contrast×100. Both study groups were matched in clinical and laboratory data, as well as volume of injected contrast. In CSA group, mean fraction of aspirated contrast was 39.35±10.47%. One patient in the CSA group, compared with 9 patients in the control group, developed contrast-induced acute kidney injury (
P
=0.028).

Conclusions—
CSA during coronary angiography could effectively remove more than one third of the given contrast and may reduce the incidence of contrast-induced acute kidney injury in selected patients.
Uwagi o sowietyzmach w polszczyźnie etnicznej i radzieckiej w dwudziestoleciu międzywojennym (na materiale „Encyklopedycznego słownika wyrazów obcych. Pochodzenie wyrazów, wymowa, objaśnienia pojęć, skróty, przysłowia, cytaty” Trzaski, Everta, Michalskiego i moskiewskiej „Trybuny Radzieckiej” z lat 1927–1938)
Authors: Graczykowska Tamara 
Published: January 2017

Observations on the Soviet Vocabulary in the Ethnic Polish Language and the Soviet Polish Language in the Interwar Period (Based on Trzaska-Evert-Michalski “Encyclopedic Dictionary of Foreign Words” and “Trybuna Radziecka,” 1927–1938)The paper discusses the Soviet vocabulary extracted from “Trybuna Radziecka”, a cen­tral Polish weekly published in Moscow in 1927–1938 and edited by Polish left‑wing intelligentsia, living in the USRR as political émigrés in this period as well as some Sovietisms included in the Encyclopedic Dictionary of Foreign Words, edited by S. Lam, published by Trzaska-Evert-Michalski in Warsaw in 1939. The author tries to demon­strate that the new realities of life and state power in the Soviet Union had immense influence on the Polish language in Russia in the interwar period, and especially on the language of “Trybuna Radziecka.” This weekly was imbued with Sovietisms. They were in common use of the Poles living in Soviet Russia in the interwar period. The Soviet vocabulary in Trzaska-Evert-Michalski dictionary represents two layers. The first one includes lexical items fully assimilated by the Polish language, e.g. kołchoz, komsomolec. The second one contains exotic words, used occasionally, e.g. ispołkom, krasnoarmiejec, otlicznik, piatiletka. Uwagi o sowietyzmach w polszczyźnie etnicznej i radzieckiej w dwudziestoleciu międzywojennym (na materiale Encyklopedycznego słownika wyrazów obcych. Pochodzenie wyrazów, wymowa, objaśnienia pojęć, skróty, przysłowia, cytaty Trzaski, Everta, Michalskiego i moskiewskiej „Trybuny Radzieckiej” z lat 1927–1938)W artykule omówiono słownictwo radzieckie zarejestrowane w Encyklopedycznym słowniku wyrazów obcych wydanym w 1939 r. w Warszawie przez Trzaskę, Everta, Michalskiego, pod redakcją S. Lama i jednocześnie odzwierciedlone w „Trybunie Radzieckiej”, która ukazywała się w Moskwie w latach 1927–1938. Sowietyzmy zamieszczone w słowniku Trzaski i in. można podzielić na dwie grupy. Pierwszą grupę stanowią wyrazy, które nigdy nie były w powszechnym użyciu w komunikacji językowej Polaków, mogły się pojawiać okazjonalnie w tekstach publicystycznych, zyskując odcień żartobliwy czy ironiczny. Zapożyczenia te nie są zasymilowane (np. ispołkom, krasnoarmiejec, otlicznik, piatiletka). Grupę drugą tworzą wyrazy będące jedynymi nazwami określonych desygnatów, niezbędnych do opisania socjalistycznej rzeczywistości w Rosji radzieckiej. Są one całkowicie przyswojone przez język polski (np. agitka, kołchoz, komsomolec). W odróżnieniu od polszczyzny ogólnej, w pore­wolucyjnej polszczyźnie radzieckiej wszystkie te jednostki występowały bez żadnych ograniczeń (często świadczy o tym ich duża frekwencja tekstowa oraz rejestracja w innych źródłach radzieckich).
Słowniki w Wielkim Księstwie Litewskim – przyczynek do historii (zachodnio)ruskiej leksykografii i leksyki
Authors: Citko Lilia 
Published: January 2017

Dictionaries in the Grand Duchy of Lithuania – a Contribution to the History of (Western)Ruthenian Lexicography and Word-Inventory In the article an attempt to describe the oldest Western Ruthenian dictionary has been made. The analysis is based on the following texts: 1) Leksis s tolkovanīem slovenskikh mov prosto of the first part of the 16th century, 2) Leksis siriech rechenïia v"krat"tsie s"bran(")ny. I īz slove(n)skago iazyka naprosty(ĭ) ruskīĭ diale(k)t istol(")kovany L,Z by L. Zizaniy (Vilno 1596), 3) Leksīkon slavenorosskīĭ ī imen tl"kovanīe by P. Berynda (Kiev 1627), 4) Sinonima slavenorosskaia (the end of the 17th century). The focus of attention is directed to lexicographic specificity of the antique texts, the elements of their macro- and microstructures, sources and techniques of material documentation, which made it possible to observe the evolution of lexicographers` methodological procedure in the range of the structure of an entry, e.g.: efforts to introduce grammatical information, qualifiers (mostly etymological and stylistic), and material exemplification.Dictionaries, which were essentially used to learn the language of liturgical celebration, contained religious vocabulary. It should be noted, however, that their authors introduced Ruthenian words of various thematic groups and stylistic registers to the translated parts of lexicons. In Berynda`s dictionary Polish loan words appeared as entries. Słowniki w Wielkim Księstwie Litewskim – przyczynek do historii (zachodnio)ruskiej leksykografii i leksykiW artykule podjęto próbę charakterystyki najstarszych słowników zachodnioru­skich na podstawie kilku źródeł: 1) Leksis s tolkovanīem slovenskikh mov prosto z pierwszej połowy XVI w.; 2) Leksis siriech rechenïia v"krat"tsie s"bran(")ny. I īz slove(n)skago iazyka naprosty(ĭ) ruskīĭ diale(k)t istol(")kovany L,Z W. Zizaniego (Wilno 1596); 3) Leksīkon slavenorosskīĭ ī imen tl"kovanīe P. Beryndy (Kijów 1627); 4) Sinonima slavenorosskaia (koniec XVII w.). Głównie uwagę skupiono na specyfice leksykograficznej zabytków, elementach ich makro-i mikrostruktury, źródłach oraz sposobach dokumentacji materiału. Pozwoliło to zaobserwować pewną ewolucję warsztatu metodologicznego leksykografów w zakresie budowy artykułu hasłowego, jak np. próby wprowadzania informacji gramatycznej, kwalifikatorów (głównie etymologicznych, stylistycznych) oraz egzemplifikacji materiałowej.Słowniki, przeznaczone zasadniczo do nauki języka liturgicznego i lektury ksiąg cerkiewnych, gromadziły przede wszystkim leksykę religijną. Należy jednak zauważyć, że do przekładowej części leksykonów ich autorzy wprowadzali słownictwo ruskie należące do różnych grup tematycznych i rejestrów stylistycznych. W charakterze wyrazów hasłowych słownika Beryndy mogły występować również pożyczki polskie.
The Use of the Lexical Exponents of Hypothetical Modality in Polish and Lithuanian
Authors: Roszko Danuta 
Published: January 2017

The Use of the Lexical Exponents of Hypothetical Modality in Polish and LithuanianIn this article the author focuses on the issue of hypothetical modality[1] in Polish and Lithuanian. A list of the basic exponents of hypothetical modality in both languages is presented. However, the focus is mainly placed on the lexical exponents. On the basis of one of the six groups, which describes a high degree of probability (H5), the differences between the use of the lexical exponents in both languages are examined. In the study, multilingual corpora resources, including The Polish-Lithuanian parallel corpus Clarin-PL., are utilized.[1] [In the academic literature, for the notion described herein, the term of epistemic modality is also used. Nevertheless, in this paper I will continue to use the term of hypotheticality, which I borrowed from the studies on modality, conducted in Polish-Bulgarian cooperation (Slavic Institute of Polish Academy of Sciences and Institute for Bulgarian Language of the Bulgarian Academy of Sciences).] O użyciu wykładników leksykalnych modalności hipotetycznej w językach polskim i litewskimW artykule autorka porusza zagadnienie modalności hipotetycznej[1] w językach polskim i litewskim. Przedstawia wykaz podstawowych wykładników modalności hipotetycznej w obu językach. Główną uwagę skupia jednak na wykładnikach leksykalnych. Na przykładzie jednej z sześciu grup, opisującej wysoki stopień prawdopodobieństwa (H5), omawia różnice użycia wykładników leksykalnych w obu językach. W badaniach wykorzystuje wielojęzyczne zasoby korpusowe, w tym Polsko-litewski korpus równoległy Clarin-PL.[1] [W literaturze przedmiotu na oznaczenie opisywanych tu treści stosowany jest również termin epistemiczności. Niemniej jednak w tej pracy autorka pozostaje przy terminie hipotetyczności, który zapożycza z badań nad modalnością, prowadzonych we współpracy polsko-bułgarskiej (Instytut Slawistyki PAN i Instytut Języka Bułgarskiego BAN).]
NFLUX Satellite-Based Surface Radiative Heat Fluxes. Part I: Swath-Level Products
Authors: May Jackie C. , Rowley Clark , Barron Charlie N. 
Published: January 2017

AbstractThe Naval Research Laboratory (NRL) ocean surface flux (NFLUX) system originally provided operational near-real-time satellite-based surface state parameter and turbulent heat flux fields over the global ocean. This study extends the NFLUX system to include the production of swath-level shortwave and longwave radiative heat fluxes at the ocean surface. A companion paper presents the production of the satellite-based global gridded radiative heat flux analysis fields. The swath-level radiative heat fluxes are produced using the Rapid Radiative Transfer Model for Global Circulation Models (RRTMG), with the primary inputs of satellite-derived atmospheric temperature and moisture profiles and cloud information retrieved from the Microwave Integrated Retrieval System (MIRS). This study uses MIRS data provided for six polar-orbiting satellite platforms. Additional inputs to the RRTMG include sea surface temperature, aerosol optical depths, atmospheric gas concentrations, ocean surface albedo, and ocean surface emissivity. Swath-level shortwave flux estimates are converted into clearness index values, which are used in data assimilation because the clearness index values are less dependent on the solar zenith angle. The NFLUX swath-level shortwave flux, longwave flux, and clearness index estimates are produced for 1 May 2013–30 April 2014 and validated against observations from research vessel and moored buoy platforms. Each of the flux parameters compares well among the various satellites.
Inversion of Potential Vorticity Density
Authors: Egger Joseph , Hoinka Klaus-Peter , Spengler Thomas 
Published: January 2017

Abstract
Inversion of potential vorticity density with absolute vorticity and function η is explored in η coordinates. This density is shown to be the component of absolute vorticity associated with the vertical vector of the covariant basis of η coordinates. This implies that inversion of in η coordinates is a two-dimensional problem in hydrostatic flow.
Examples of inversions are presented for (θ is potential temperature) and (p is pressure) with satisfactory results for domains covering the North Pole. The role of the boundary conditions is investigated and piecewise inversions are performed as well. The results shed new light on the interpretation of potential vorticity inversions.
Developing a Convective-Scale EnKF Data Assimilation System for the Canadian MEOPAR Project
Authors: Jacques Dominik , Chang Weiguang , Baek Seung-Jong , Milewski Thomas , Fillion Luc , Chung Kao-Shen , Ritchie Harold 
Published: January 2017

Abstract
This study discusses the construction of a high-resolution ensemble Kalman filter system (the HREnKF) developed for the Marine Environmental Observation Prediction and Response (MEOPAR) network. The HREnKF runs at a horizontal resolution of 2.5 km and is intended to provide forecasts at lead times up to 12 h. This system was adapted from the global EnKF system in operation at Environment and Climate Change Canada. As a first development step, only the most necessary modifications have been implemented. The changes include an hourly cycling frequency, smaller localization radii, and the explicit representation of microphysical processes. To assess its performance and orient future developments, the HREnKF was continuously cycled for a period of 12 days. Verification against surface observations reveals that the skill of the forecasts initialized from the HREnKF is comparable to that of control forecasts also integrated at a resolution of 2.5 km. A key component of this study is the comparison of correlation estimated from ensembles at resolutions of 2.5, 15, and 50 km. At 2.5 km, correlation lengths are smaller than those found at 15 and 50 km. These short correlation lengths demand a high observational density, which is not available over the west coast domain where the HREnKF was tested. The spatial and temporal variability of the correlations is also assessed for the HREnKF system. It is found that correlation patterns are complex and do not generally decrease monotonically away from the reference point around which they are estimated. This result is important as it indicates that separation distance may not be the ideal parameter to use as a basis for localization strategies.
CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors
Authors: Hughes Amy , Clarson Jade , Tang Carine , Vidovic Ljiljana , White Deborah L. , Hughes Timothy P. , Yong Agnes S. M. 
Published: January 2017

Key Points
Increased immune suppressors and PD-1 abrogates effector responses in CML patients at diagnosis. Enhanced net effector immune responses and decreased PD-1 and immune suppressors may promote sustained deep molecular response in CML.
Phase angle is associated with the length of ICU stay in patients with non-ST elevation acute coronary syndrome
Authors: Polegato Bertha Furlan , Herrera Monique Aguilar , Pereira Bruna Letícia Buzati , Silva Renata Aparecida Candido , Gonçalves Andrea Freitas , Cavallari Karelin Alvisi , Costa Nara Aline , Tanni Suzana Erico , Azevedo Paula Schmidt , Dorna Mariana Souza , Zornoff Leonardo Antonio Mamede , de Paiva Sergio Alberto Rupp , Minicucci Marcos Ferreira 
Published: January 2017

Abstract
Background
The aim of this study was to evaluate the associations between phase angle (PhA), sarcopenia, and the length of stay (LOS) in the coronary intensive care unit (ICU) in patients with non-ST acute coronary syndrome (NSTE-ACS).

Methods
This was a prospective observational study that evaluated 80 patients with NSTE-ACS over the age of 18 years, admitted to the ICU from January to June 2014. Upon admission, the patients’ demographic information was recorded. Handgrip strength and bioelectrical impedance analysis (BIA) were performed, and blood samples were taken within the first 72 h of admission. All of the patients were followed during their ICU stays.

Results
We evaluated 80 patients, five were excluded due to impossibility of assessing handgrip strength, and seven patients were not subjected to BIA. Thus, 68 patients with a mean age of 63.3 ± 13.1 years were included in the analysis. Among these patients, 60.1% were male, 27.9% of the patients had sarcopenia, 8.8% had LOSs ≥8 days, and median phase angle was 6.5 (6.1–7.3)°. Multiple logistic regression adjusted for age and gender revealed that PhA was not associated with the presence of sarcopenia. Additionally, PhA (OR 0.337; CI 95% 0.118–0.961; p = 0.04) but not sarcopenia (OR 0.517; CI 95% 0.055–4.879; p = 0.56) was associated with an increased LOS.

Conclusions
PhA is associated with LOS in patients with NSTE-ACS. Additionally, there was no association between PhA and sarcopenia.