bluuebunny/crossref_metadata_2025_split huggingface dataset:
FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression
Authors: Gopal Keshav , Saleme Bruno , Al Batran Rami , Aburasayn Hanin , Eshreif Amina , Ho Kim L. , Ma Wayne K. , Almutairi Malak , Eaton Farah , Gandhi Manoj , Park Edwards A. , Sutendra Gopinath , Ussher John R. 
Published: July 2017

Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme for glucose oxidation and a critical regulator of metabolic flexibility during the fasting to feeding transition. PDH is regulated via both PDH kinases (PDHK) and PDH phosphatases, which phosphorylate/inactivate and dephosphorylate/activate PDH, respectively. Our goal was to determine whether the transcription factor forkhead box O1 (FoxO1) regulates PDH activity and glucose oxidation in the heart via increasing the expression of Pdk4, the gene encoding PDHK4. To address this question, we differentiated H9c2 myoblasts into cardiac myocytes and modulated FoxO1 activity, after which Pdk4/PDHK4 expression and PDH phosphorylation/activity were assessed. We assessed binding of FoxO1 to the Pdk4 promoter in cardiac myocytes in conjunction with measuring the role of FoxO1 on glucose oxidation in the isolated working heart. Both pharmacological (1 µM AS1842856) and genetic (siRNA mediated) inhibition of FoxO1 decreased Pdk4/PDHK4 expression and subsequent PDH phosphorylation in H9c2 cardiac myocytes, whereas 10 µM dexamethasone-induced Pdk4/PDHK4 expression was abolished via pretreatment with 1 µM AS1842856. Furthermore, transfection of H9c2 cardiac myocytes with a vector expressing FoxO1 increased luciferase activity driven by a Pdk4 promoter construct containing the FoxO1 DNA-binding element region, but not in a Pdk4 promoter construct lacking this region. Finally, AS1842856 treatment in fasted mice enhanced glucose oxidation rates during aerobic isolated working heart perfusions. Taken together, FoxO1 directly regulates Pdk4 transcription in the heart, thereby controlling PDH activity and subsequent glucose oxidation rates. NEW & NOTEWORTHY Although studies have shown an association between FoxO1 activity and pyruvate dehydrogenase kinase 4 expression, our study demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart.
Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation
Authors: Bhagat Tushar D. , Chen Si , Bartenstein Matthias , Barlowe A. Trevor , Von Ahrens Dagny , Choudhary Gaurav S. , Tivnan Patrick , Amin Elianna , Marcondes A. Mario , Sanders Mathijs A. , Hoogenboezem Remco M. , Kambhampati Suman , Ramachandra Nandini , Mantzaris Iaonnis , Sukrithan Vineeth , Laurence Remi , Lopez Robert , Bhagat Prafulla , Giricz Orsi , Sohal Davendra , Wickrema Amittha , Yeung Cecilia , Gritsman Kira , Aplan Peter , Hochedlinger Konrad , Yu Yiting , Pradhan Kith , Zhang Jinghang , Greally John M. , Mukherjee Siddhartha , Pellagatti Andrea , Boultwood Jacqueline , Will Britta , Steidl Ulrich , Raaijmakers Marc H.G.P. , Deeg H. Joachim , Kharas Michael G. , Verma Amit 
Published: July 2017

Abstract
The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow–derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine–treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34+ cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98–HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846–57. ©2017 AACR.
Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer
Authors: Walter Katherine R. , Goodman Merit L. , Singhal Hari , Hall Jade A. , Li Tianbao , Holloran Sean M. , Trinca Gloria M. , Gibson Katelin A. , Jin Victor X. , Greene Geoffrey L. , Hagan Christy R. 
Published: July 2017

Abstract
The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to IFN treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR's ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. IFN activation is a critical early step in nascent tumor recognition and destruction through immunosurveillance. As the large majority of breast tumors are PR positive at the time of diagnosis, PR-dependent downregulation of IFN signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors.
Implications: This study highlights a novel transcriptional mechanism through which PR drives breast cancer development and potentially evades the immune system. Mol Cancer Res; 15(10); 1331–40. ©2017 AACR.
Rights, Obligations, Prohibitions: A Practical Guide to Understanding Judicial Decisions on Coastal State Jurisdiction over Living Resources in the Exclusive Economic Zone
Authors: Goodman Camille 
Published: July 2017

Abstract
Given the ambiguous, open-ended and highly qualified nature of the legal framework governing the coastal State’s regulation of living resources in the exclusive economic zone (EEZ), there is an important role for international courts and tribunals in reviewing the innovations and interpretations offered by coastal States, and clarifying the meaning of relevant provisions. In light of the significant body of jurisprudence that is now available in this area, this article seeks to provide some practical guidance regarding the nature and extent of coastal State jurisdiction over living resources in the EEZ, by reference to the approaches taken by international courts and tribunals.
Statistical Prediction of Winter Haze Days in the North China Plain Using the Generalized Additive Model
Authors: Yin Zhicong , Wang Huijun 
Published: July 2017

AbstractWinter (December–February) haze days in the North China Plain (WHDNCP) have recently dramatically increased. In addition to human activities, climate change and variability also contributed to the severe situation and supported the possibility of seasonal predictions. In this study, using the generalized additive model (GAM), the sea surface temperature around the Alaska Gulf and sea ice area of the Beaufort Sea were selected as the predictors to establish a statistical prediction model (SPM). The difference between the current and previous year of WHDNCP (WDY) was predicted first and was then added to the observation of the previous year to obtain the final predicted WHDNCP. For WDY prediction, the root-mean-square error of the SPM using GAM was 3.01 days. In addition to the annual variation, the tropospheric biennial oscillation features and the dramatically increasing trend after 2010 were both captured successfully. Furthermore, for the final predicted WHDNCP anomalies, the long-term trend and turning points were simulated well, and the percentage of the same mathematical sign was 91.7%. Independent prediction tests were performed for 2014 and 2015, and the forecast bias was 0.86 and 0.19 days, respectively. To assess the predictive ability, recycling independent tests (including real-time hindcasts for the period 2005–15) were also applied, and the percentage of the same sign was 100%.
Evaluation of CMIP5 Model Precipitation Using PERSIANN-CDR
Authors: Nguyen Phu , Thorstensen Andrea , Sorooshian Soroosh , Zhu Qian , Tran Hoang , Ashouri Hamed , Miao Chiyuan , Hsu KuoLin , Gao Xiaogang 
Published: July 2017

Abstract
The purpose of this study is to use the PERSIANN–Climate Data Record (PERSIANN-CDR) dataset to evaluate the ability of 32 CMIP5 models in capturing the behavior of daily extreme precipitation estimates globally. The daily long-term historical global PERSIANN-CDR allows for a global investigation of eight precipitation indices that is unattainable with other datasets. Quantitative comparisons against CPC daily gauge; GPCP One-Degree Daily (GPCP1DD); and TRMM 3B42, version 7 (3B42V7), datasets show the credibility of PERSIANN-CDR to be used as the reference data for global evaluation of CMIP5 models. This work uniquely defines different study regions by partitioning global land areas into 25 groups based on continent and climate zone type. Results show that model performance in warm temperate and equatorial regions in capturing daily extreme precipitation behavior is largely mixed in terms of index RMSE and correlation, suggesting that these regions may benefit from weighted model averaging schemes or model selection as opposed to simple model averaging. The three driest climate regions (snow, polar, and arid) exhibit high correlations and low RMSE values when compared against PERSIANN-CDR estimates, with the exceptions of the cold regions showing an inability to capture the 95th and 99th percentile annual total precipitation characteristics. A comprehensive assessment of each model’s performance in each continent–climate zone defined group is provided as a guide for both model developers to target regions and processes that are not yet fully captured in certain climate types, and for climate model output users to be able to select the models and/or the study areas that may best fit their applications of interest.
Evaluating the Global Internal Wave Model IDEMIX Using Finestructure Methods
Authors: Pollmann Friederike , Eden Carsten , Olbers Dirk 
Published: July 2017

AbstractSmall-scale turbulent mixing affects large-scale ocean processes such as the global overturning circulation but remains unresolved in ocean models. Since the breaking of internal gravity waves is a major source of this mixing, consistent parameterizations take internal wave energetics into account. The model Internal Wave Dissipation, Energy and Mixing (IDEMIX) predicts the internal wave energy, dissipation rates, and diapycnal diffusivities based on a simplification of the spectral radiation balance of the wave field and can be used as a mixing module in global numerical simulations. In this study, it is evaluated against finestructure estimates of turbulent dissipation rates derived from Argo float observations. In addition, a novel method to compute internal gravity wave energy from finescale strain information alone is presented and applied. IDEMIX well reproduces the magnitude and the large-scale variations of the Argo-derived dissipation rate and energy level estimates. Deficiencies arise with respect to the detailed vertical structure or the spatial extent of mixing hot spots. This points toward the need to improve the forcing functions in IDEMIX, both by implementing additional physical detail and by better constraining the processes already included in the model. A prominent example is the energy transfer from the mesoscale eddies to the internal gravity waves, which is identified as an essential contributor to turbulent mixing in idealized simulations but needs to be better understood through the help of numerical, analytical, and observational studies in order to be represented realistically in ocean models.
Mesoscale and Submesoscale Effects on Mixed Layer Depth in the Southern Ocean
Authors: Bachman S. D. , Taylor J. R. , Adams K. A. , Hosegood P. J. 
Published: July 2017

AbstractSubmesoscale dynamics play a key role in setting the stratification of the ocean surface mixed layer and mediating air–sea exchange, making them especially relevant to anthropogenic carbon uptake and primary productivity in the Southern Ocean. In this paper, a series of offline-nested numerical simulations is used to study submesoscale flow in the Drake Passage and Scotia Sea regions of the Southern Ocean. These simulations are initialized from an ocean state estimate for late April 2015, with the intent to simulate features observed during the Surface Mixed Layer at Submesoscales (SMILES) research cruise, which occurred at that time and location. The nested models are downscaled from the original state estimate resolution of 1/12° and grid spacing of about 8 km, culminating in a submesoscale-resolving model with a resolution of 1/192° and grid spacing of about 500 m. The submesoscale eddy field is found to be highly spatially variable, with pronounced hot spots of submesoscale activity. These areas of high submesoscale activity correspond to a significant difference in the 30-day average mixed layer depth between the 1/12° and 1/192° simulations. Regions of large vertical velocities in the mixed layer correspond with high mesoscale strain rather than large . It is found that is well correlated with the mesoscale density gradient but weakly correlated with both the mesoscale kinetic energy and strain. This has implications for the development of submesoscale eddy parameterizations that are sensitive to the character of the large-scale flow.
Mandibular Lytic Lesion in Familial Paraganglioma Syndrome Type I: A Clinical Conundrum
Authors: Sinha Parul , Yuen Sonia N. , Chernock Rebecca D. , Haughey Bruce H. 
Published: July 2017

Objective: The entity of primary mandibular paraganglioma (PGL) is not well accepted within the head and neck. Mandibular PGLs hitherto reported in literature are malignant metastatic lesions, mostly from a pheochromocytoma. Methods: We report a case of mandibular lytic lesion in a young female with multifocal PGLs but no family history of PGLs. We also performed a literature search to identify published cases of mandibular PGL. Results: Lack of established criteria for malignancy in a PGL made diagnosis and treatment challenging. Testing was negative for a pheochromocytoma and positive for mutation of succinate dehydrogenase gene encoding subunit D (SDHD), thus rendering a diagnosis of familial PGL syndrome type I. Due to the absence of prior published reports of nonmalignant, primary mandibular PGL, patient was treated with surgery and postoperative radiotherapy. Our literature search revealed 4 published cases of mandibular PGL, all of which had an osteoblastic appearance and were malignant. Conclusions: Isolated mandibular PGL does not always indicate a malignant metastatic lesion. Genetic testing is recommended in patients with early onset of PGL and/or multifocality even without a positive family history. Surgical resection alone with surveillance can be offered for such isolated lesions in the presence of familial PGL syndrome type I.
From Childhood Experience to ARS Poetica: Forming Substitutes
Authors: De Vincenti Gloria 
Published: July 2017

In 1915 Sigmund Freud began a series of three sets of introductory lectures on psychoanalysis, at the University of Vienna. During the 23rd lecture, delivered in 1917, he engaged in a discussion on the conflict between the realm of phantasy and the reality-principle. Towards the conclusion, though, he envisaged a resolution and declared that “there is a path from phantasy to reality — the path, that is, of art.” In 1915 the artist and writer Arnaldo Ginna, one of the prominent figures of the Second Florentine Futurism avant-garde movement, had been investigating the function of artistic creation in relation to dreams, namely “to evoke in the most real reality the visions that have been dreams so far.” This paper explores the significance of the creative process and the mechanisms involved in the shift from phantasy to reality. Taking a Freudian standpoint, the analysis brings the Futurists' theoretical contribution into the discussion. The study demonstrates how the artist reconnects the self, on a public ground, with the legacy of childhood which endures within us.
Price Competitiveness of India's Exports to Asean
Authors: Sarkar Amal 
Published: July 2017

India emphasized the look east policy since early nineties. As a part of its export promotion strategy, it is essential to know the key determinants of export of these products to ASEAN. In this direction, the present paper has made an attempt to find the main determinants of India's exports of the major commodity groups to ASEAN. The top ten commodity groups, which have been found in this study, are gems & jewellery, machinery & instruments, dyes & intermediates, primary & semi-finished iron & steel, oil meal, drugs/pharmaceuticals & fine chemicals, transport equipment, electronic goods, inorganic/organic/agro-based chemicals, and manufactures of metals in recent years. Among these items, gems & jewellery, machinery & instruments, dyes & intermediates and transport equipment have registered higher growth in last five years. To explore the determinants, an export demand function has been formulated at the commodity level. As regards to results, it has performed very well in terms of sign and significance of the explanatory variables. It can be said that all the commodities under study, except oil-meal, are not only price competitive in the ASEAN market but also very much elastic in demand. These elasticities are indicative of the fact that real devaluation of Indian rupee against dollar has high impact on India's export of these products to ASEAN market. Further, economic growth in ASEAN region would also be helpful for expanding India's exports of these products to that region. This study reveals valuable insight for policymakers in formulating either a commercial or exchange rate policy.
Simultaneous Interpretation: Temporal and Quantitative Data
Authors: Barik Henri C. 
Published: July 2017

Simultaneous interpretation represents a complex form of activity, about which there is very little in the way of experimental data. In an exploratory study, two professional, two student and two amateur interpreters (one English-dominant and one French-dominant in each case) were required to do the interpretation of several texts from either their weaker into their dominant language or vice-versa. The texts represented four types of material: spontaneous speech, semi-prepared material, prepared " oral " material, and prepared " written " material. Presentation of texts and recording of translations was on tape. The temporal characteristics of the speaker (S) and interpreter or translator (T) delivery patterns and their interrelationship were analysed by computer. Translated speech per se is found to generally present the same patterns and relationships among speech parameters as natural speech, but to be less rhythmical. In omission-free translation T tends to be engaged in speaking for a greater proportion of time than S, largely because of slower articulation. Proportionally more of the T's utterance is delivered while the S is pausing than would be expected were the two delivery patterns independent; thus the T tries to take advantage of the S's pauses and thereby reduce the extent of time during which he must be both speaking and listening at the same time. Characteristically, the T lags behind the S in his delivery by 2 to 3 sec. The temporal data do not in general reveal striking differences in relation to the different categories of T, the various types of material, or the two directions of translation.
Schizophrenic Speech : a Factor-Analytic Approach
Authors: Gerver D. , Lawson J.S. , Gerver M.E. 
Published: July 2017

Verbal responses were obtained to two questions from the Wechsler Adult Intelligence Scale Comprehension Sub-test from three groups of subjects matched for age and verbal I.Q.: schizoprhenic patients, non-schizophrenic psychiatric hospital patients, normal controls. These responses were rated by 11 graduate clinical psychology students on 15 four point scales based mainly on adjectives used in the psychiatric literature to describe " schizophrenic language ". Varimax rotations of principal components analyses of the ratings revealed two main factors accounting for approximately 93% of the total variance for all ratings: a structural (syntactic) factor and a semantic factor. This finding is discussed in terms of its implications for diagnosis and for the clinical description of the language of schizophrenics.
Sentence Comprehension and Short-Term Memory : Some Developmental Considerations
Authors: Scholes Robert J. , Rasbury Wiley C. , Scholes Irene B. , Dowling Katy 
Published: July 2017

Four types of stimuli—digit strings, noun phrases plus digit strings, intransitive sentences plus digit strings, and transitive sentences plus digit strings—were presented to subjects for immediate recall. Three groups of subjects were tested: 20 seven-year olds, 20 ten-year olds, and 20 adults. Sentence recall errors and digit spans for each condition are considered in terms of the age of the subjects. Analyses indicate that while digit span for the digit only condition shows a steadily rising function across ages, digit spans for the verbal conditions show irregular slopes, the conditions changing relative positions across ages. Discussion of the results centres on the separate aspects of the maturational increase in short-term memory and the acquisition of linguistic mediational strategies (i.e., " chunking ").