bluuebunny/crossref_metadata_2025_split huggingface dataset:
EWS/FLI1 Regulates EYA3 in Ewing Sarcoma via Modulation of miRNA-708, Resulting in Increased Cell Survival and Chemoresistance
Authors: Robin Tyler P. , Smith Anna , McKinsey Erin , Reaves Lisa , Jedlicka Paul , Ford Heide L. 
Published: June 2012

AbstractEwing sarcoma is an aggressive pediatric cancer of the bone and soft tissue, in which patients whose tumors have a poor histologic response to initial chemotherapy have a poor overall prognosis. Therefore, it is important to identify molecules involved in resistance to chemotherapy. Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor. We further show that EWS/FLI1 mediates upregulation of EYA3 via repression of miR-708, a miRNA that targets the EYA3 3′-untranslated region, rather than by binding the EYA3 promoter directly. Importantly, we show that high levels of EYA3 significantly correlate with low levels of miR-708 in Ewing sarcoma samples, suggesting that this miR-mediated mechanism of EYA3 regulation holds true in human cancers. Because EYA proteins are important for cell survival during development, we examine, and show, that loss of EYA3 decreases survival of Ewing sarcoma cells. Most importantly, knockdown of EYA3 in Ewing sarcoma cells leads to sensitization to DNA-damaging chemotherapeutics used in the treatment of Ewing sarcoma, and as expected, after chemotherapeutic treatment, EYA3 knockdown cells repair DNA damage less effectively than their control counterparts. These studies identify EYA3 as a novel mediator of chemoresistance in Ewing sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance. Mol Cancer Res; 10(8); 1098–108. ©2012 AACR.
Insulin Activation of Plasma Nonesterified Fatty Acid Uptake in Metabolic Syndrome
Authors: Ramos-Roman Maria A. , Lapidot Smadar A. , Phair Robert D. , Parks Elizabeth J. 
Published: June 2012

Objective—
Insulin control of fatty acid metabolism has long been deemed dominated by suppression of adipose lipolysis. The goal of the present study was to test the hypothesis that this single role of insulin is insufficient to explain observed fatty acid dynamics.

Methods and Results—

Fatty acid kinetics were measured during a meal tolerance test and insulin sensitivity assessed by intravenous glucose tolerance test in overweight human subjects (n=15; body mass index, 35.8±7.1 kg/m
2
). Non–steady state tracer kinetic models were formulated and tested using ProcessDB software. Suppression of adipose fatty acid release, by itself, could not account for postprandial nonesterified fatty acid concentration changes, but adipose suppression combined with insulin activation of fatty acid uptake was consistent with the measured data. The observed insulin
K

m

for nonesterified fatty acid uptake was inversely correlated with both insulin sensitivity of glucose uptake (intravenous glucose tolerance test insulin sensitivity;
r
=−0.626;
P
=0.01) and whole body fat oxidation after the meal (
r
=−0.538;
P
=0.05).

Conclusion—
These results support insulin regulation of fatty acid turnover by both release and uptake mechanisms. Activation of fatty acid uptake is consistent with the human data, has mechanistic precedent in cell culture, and highlights a new potential target for therapies aimed at improving the control of fatty acid metabolism in insulin–resistant disease states.
Thin-Slice Reconstructions of Nonenhanced CT Images Allow for Detection of Thrombus in Acute Stroke
Authors: Riedel Christian H. , Zoubie Julia , Ulmer Stephan , Gierthmuehlen Janne , Jansen Olav 
Published: June 2012

Background and Purpose—
The purpose of this study was to investigate whether thin-slice image reconstructions of cranial nonenhanced CT scans could be used to significantly increase sensitivity for detecting intraluminal thrombus in patients with acute ischemic stroke due to proximal occlusion of the middle cerebral artery.

Methods—
In a prospective case series, the raw data of nonenhanced CT scans from 54 patients presenting with acute ischemic stroke and proven vascular obliteration of the middle cerebral artery were collected along with the same data from patients not having a stroke but the same sex and age. All raw data were reconstructed with a slice thickness of 5 mm and as thin slices with a thickness of 0.625 mm. Three observers independently evaluated the 5-mm nonenhanced CT reconstructions and 5-mm maximum intensity projections of the thin slices and rated the likelihood of a clot obliterating the middle cerebral artery trunk or first-order branches using a 5-point scale. The results were evaluated in comparison with base data using receiver operating curve analysis. Interobserver agreement was measured using Cohen κ for every pair of observers.

Results—
The area under the curve for the receiver operating curve analysis for the thick slices ranged from 0.63 to 0.67, whereas for the maximum intensity projection images of the thin slice reconstructions, receiver operating curve analysis revealed areas under the curve between 0.94 and 0.97. Interobserver agreement was higher for thin-slice (κ, 0.69–0.83) versus thick-slice nonenhanced CT reconstructions (κ, 0.38–0.45).

Conclusions—
Thin-slice reconstructions of standard cranial nonenhanced CT raw data allow for more sensitive and reliable detection of clots occluding the proximal middle cerebral artery.
Influences of ENSO Teleconnection on the Persistence of Sea Surface Temperature in the Tropical Indian Ocean
Authors: Ding Ruiqiang , Li Jianping 
Published: June 2012

Abstract
This study confirms a weak spring persistence barrier (SPB) of sea surface temperature anomalies (SSTAs) in the western tropical Indian Ocean (WIO), a strong fall persistence barrier (FPB) in the South China Sea (SCS), and the strongest winter persistence barrier (WPB) in the southeastern tropical Indian Ocean (SEIO). During El Niño events, a less abrupt sign reversal of SSTAs occurs in the WIO during spring, an abrupt reversal occurs in the SCS during fall, and the most abrupt reversal occurs in the SEIO during winter. The sign reversal of SSTA implies a rapid decrease in SSTA persistence, which is favorable for the occurrence of a persistence barrier. The present results indicate that a more abrupt reversal of SSTA sign generally corresponds to a more prominent persistence barrier. El Niño–induced changes in atmospheric circulation result in reduced evaporation and suppressed convection. This in turn leads to the warming over much of the TIO basin, which is an important mechanism for the abrupt switch in SSTA, from negative to positive, in the northern SCS and SEIO. The seasonal cycle of the prevailing surface winds has a strong influence on the timing of the persistence barriers in the TIO.
The Indian Ocean dipole (IOD) alone can cause a weak WPB in the SEIO. El Niño events co-occurring with positive IOD further strengthen the SEIO WPB. The SEIO WPB appears to be more strongly influenced by ENSO than by the IOD. In contrast, the WIO SPB and the SCS FPB are relatively independent of the IOD.
Does Net E − P Set a Preference for North Atlantic Sinking?
Authors: Huisman Selma E. , Dijkstra Henk A. , von der Heydt A. S. , de Ruijter W. P. M. 
Published: June 2012

Abstract
The present-day global meridional overturning circulation (MOC) with formation of North Atlantic Deep Water (NADW) and the absence of a deep-water formation in the North Pacific is often considered to be caused by the fact that the North Pacific basin is a net precipitative, while the North Atlantic is a net evaporative basin. In this paper, the authors study the effect of asymmetries in continent geometry and freshwater fluxes on the MOC both in an idealized two-dimensional model and in a global ocean model. This study approaches the problem from a multiple equilibria perspective, where asymmetries in external factors constrain the existence of steady MOC patterns. Both this multiple equilibria perspective and the fact that a realistic global geometry is used add new aspects to the problem. In the global model, it is shown that the Atlantic forced by net precipitation can have a meridional overturning circulation with northern sinking and a sea surface salinity that resembles the present-day salinity field. The model results are suggestive of the importance of factors other than the freshwater flux asymmetries, in particular continental asymmetries, in producing the meridional overturning asymmetry.
Velocity Imprecision in Finite-Beamwidth Shipboard Doppler Sonar: A First-Generation Correction Algorithm
Authors: Pinkel Robert 
Published: June 2012

Abstract
The finite angular width of Doppler sonar beams introduces errors into the measurement of ocean velocity from moving ships. These errors are exacerbated as ship speed increases and as the acoustic scatter field becomes more inhomogeneous in space. Zooplanktonic scatters often reside in distinct quasi-isopycnal scattering layers. When measured from a moving ship, such layers appear to have a distinct velocity signature, even if the ocean is quiescent. Here, this effect is explored in a simple analytic model and a least squares algorithm is presented for remediating its signature. The algorithm corrects the measured velocity at any given depth, with the correction being a weighted sum of the depth gradient of log acoustic intensity at surrounding depths. The correction weights are a property of the specific sonar beam pattern. Once determined, they can be considered constant. The algorithm, when applied to a 50-kHz sonar on the Research Vessel (R/V) Roger Revelle, is found to remove roughly 90% of the error in vertical wavenumber spectra of shear. More sophisticated algorithms can be developed as experience with the present approach is gained.
Displaying Economic Value
Authors: Marzban Caren 
Published: June 2012

Abstract
The distinction between forecast quality and economic value in a cost–loss formulation is well known. Also well known is their complex relationship, even with some instances of a reversal between the two, where higher quality is associated with lower economic value, and vice versa. It is reasonable to expect such counterintuitive results when forecast quality and economic value—both, multifaceted quantities—are summarized by single scalar measures. Diagrams are often used to display forecast quality in order to better represent the multidimensional nature of forecast quality. Here, it is proposed that economic value be displayed as a region on a plot of hit rate versus false-alarm rate. Such a display obviates any need to summarize economic value by a scalar measure. The choice of the axes is motivated by the relative operating characteristic (ROC) diagram, and, so, this manner of displaying economic value is useful for deterministic as well as probabilistic forecasts.
Ward features and stigma experiences of mental health service users in Belgium and England: A replication study
Authors: Schneider Justine , Beeley Chris , Scales Kezia , Bailey Simon , Verhaeghe Mieke , Bracke Piet 
Published: June 2012

Background: Stigmatizing attitudes can impair the quality of life of people with mental health problems. Psychiatric hospitalization can generate stigma. Are some approaches to care less stigmatizing than others? Aims: This study was designed to replicate findings from Flanders, Belgium in an English context, investigating how ward size and treatment approach affected service users’ expectations and experiences of stigma. Methods: The translated Belgian questionnaire was administered to 70 service users in 15 inpatient adult mental health settings in central England. Adjustments were made to the multivariate analysis in light of the smaller sample size, in order to replicate the original equation as closely as possible. Results: Neither ward size nor individualized care proved significant in the smaller English sample, which was subject to the risk of type II error. Across two models, self-rejection correlated with age (negatively), social rejection and stigma expectations. Conclusions: This analysis shows that attempts to translate evidence about psychiatric inpatient services must take into account differences between the settings, populations and models of care. Expectations as well as outcomes of stigma may be relevant when assessing the impact of psychiatric hospital treatment on individual patients.
Effectiveness of a Culturally Tailored Diabetes Self-Management Program for Chinese Americans
Authors: Sun Angela C. , Tsoh Janice Y. , Saw Anne , Chan Joanne L. , Cheng Joyce W. 
Published: June 2012

Purpose The purpose of the study was to test the feasibility and efficacy of a diabetes self-management and education program for Chinese Americans in a support group format. The rationale for the study was to create culturally appropriate diabetes education and management programs in response to the growing diabetes prevalence among Chinese Americans. The investigators hypothesized that participants will have improved diabetes knowledge and practices, hemoglobin A1C, and social support. The study objectives were at least: 50% will have significant improvements in diabetes knowledge and practice activities, 30% of participants will have significant improvements in A1C, and 50% will report a gain in emotional support. Methods The program consisted of 12 90-minute diabetes education and support group sessions offered in a medical office setting. The sample included 23 Chinese Americans with either type 1 or type 2 diabetes. Using a single-group, pre-post test design, A1C and diabetes knowledge were assessed at baseline and 6 months. Data were collected through clinical assessments and written questionnaires. Results The results indicated high attendance and statistically significant increases in glycemic control and diabetes knowledge. Statistically insignificant differences were shown in diabetes management practices. Secondary outcomes assessed participants’ perceived diabetes management and emotional and social support. Conclusions Diabetes Self-Management: A Cultural Approach (DSMCA) support group model demonstrates that a culturally tailored support group utilizing a community-based participatory research approach is an effective format to improve diabetes self-management skills among Chinese Americans. The program can be adapted for other ethnic populations. The efficacy of the intervention can be further tested in larger randomized trials.
ASK1 promotes apoptosis of normal and malignant plasma cells
Authors: Lin Fan-Ru , Huang Shang-Yi , Hung Kuo-Hsuan , Su Shin-Tang , Chung Cheng-Han , Matsuzawa Atsushi , Hsiao Michael , Ichijo Hidenori , Lin Kuo-I 
Published: June 2012

Abstract
Although the overproduction of immunoglobulins by short-lived plasma cells accompanying an immune response links with their apoptosis, how long-lived plasma cells adapt to ensure their longevity in this context is obscure. Here, we show that apoptosis signal–regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells because ASK1 activity was induced during differentiation of short-lived plasma cells, and, when produced by ASK1-deficient mice, these cells survived better than those of control mice. Moreover, antigen-specific long-lived plasma cells generated by immunization accumulated in ASK1-deficient mice, suggesting ASK1 also plays a negative role in survival of long-lived plasma cells. In malignant plasma cells, ASK1 transcription was directly suppressed by B lymphocyte–induced maturation protein-1 (Blimp-1). The expression of ASK1 and Blimp-1 showed an inverse correlation between normal human mature B cells and bone marrow plasma cells from patients with multiple myeloma (MM). Suppression of ASK1 is crucial for cell survival because its enforced expression in MM cells caused apoptosis in vitro and lowered MM load in a xenograft animal model; furthermore, alteration of ASK1 activity affected MM cell survival. Our findings indicate a novel mechanism underlying the regulation of survival in normal and malignant plasma cells by ASK1.
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS
Authors: Barreyro Laura , Will Britta , Bartholdy Boris , Zhou Li , Todorova Tihomira I. , Stanley Robert F. , Ben-Neriah Susana , Montagna Cristina , Parekh Samir , Pellagatti Andrea , Boultwood Jacqueline , Paietta Elisabeth , Ketterling Rhett P. , Cripe Larry , Fernandez Hugo F. , Greenberg Peter L. , Tallman Martin S. , Steidl Christian , Mitsiades Constantine S. , Verma Amit , Steidl Ulrich 
Published: June 2012

AbstractCellular and interpatient heterogeneity and the involvement of different stem and progenitor compartments in leukemogenesis are challenges for the identification of common pathways contributing to the initiation and maintenance of acute myeloid leukemia (AML). Here we used a strategy of parallel transcriptional analysis of phenotypic long-term hematopoietic stem cells (HSCs), short-term HSCs, and granulocyte-monocyte progenitors from individuals with high-risk (−7/7q−) AML and compared them with the corresponding cell populations from healthy controls. This analysis revealed dysregulated expression of 11 genes, including IL-1 receptor accessory protein (IL1RAP), in all leukemic stem and progenitor cell compartments. IL1RAP protein was found to be overexpressed on the surface of HSCs of AML patients, and marked cells with the −7/7q− anomaly. IL1RAP was also overexpressed on HSCs of patients with normal karyotype AML and high-risk myelodysplastic syndrome, suggesting a pervasive role in different disease subtypes. High IL1RAP expression was independently associated with poor overall survival in 3 independent cohorts of AML patients (P = 2.2 × 10−7). Knockdown of IL1RAP decreased clonogenicity and increased cell death of AML cells. Our study identified genes dysregulated in stem and progenitor cells in −7/7q− AML, and suggests that IL1RAP may be a promising therapeutic and prognostic target in AML and high-risk myelodysplastic syndrome.
Preservation of Renal Function by Thyroid Hormone Replacement Therapy in Chronic Kidney Disease Patients with Subclinical Hypothyroidism
Authors: Shin Dong Ho , Lee Mi Jung , Kim Seung Jun , Oh Hyung Jung , Kim Hyoung Rae , Han Jae Hyun , Koo Hyang Mo , Doh Fa Mee , Park Jung Tak , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook 
Published: June 2012

Abstract

Context:
Subclinical hypothyroidism is not a rare condition, but the use of thyroid hormone to treat subclinical hypothyroidism is an issue of debate.

Objective:
This study was undertaken to investigate the impact of thyroid hormone therapy on the changes in estimated glomerular filtration rate (eGFR) in subclinical hypothyroidism patients with stage 2–4 chronic kidney disease.

Patients:
A total of 309 patients were included in the final analysis.

Main Outcome Measure:
The changes in eGFR over time were compared between patients with and without thyroid hormone replacement therapy using a linear mixed model. Kaplan-Meier curves were constructed to determine the effect of thyroid hormone on renal outcome, a reduction of eGFR by 50%, or end-stage renal disease. The independent prognostic value of subclinical hypothyroidism treatment for renal outcome was ascertained by multivariate Cox regression analysis.

Results:
Among the 309 patients, 180 (58.3%) took thyroid hormone (treatment group), whereas 129 (41.7%) did not (nontreatment group). During the mean follow-up duration of 34.8 ± 24.3 months, the overall rate of decline in eGFR was significantly greater in the nontreatment group compared to the treatment group (−5.93 ± 1.65 vs. −2.11 ± 1.12 ml/min/yr/1.73 m2; P = 0.04). Moreover, a linear mixed model revealed that there was a significant difference in the rates of eGFR decline over time between the two groups (P &lt; 0.01). Kaplan-Meier analysis also showed that renal event-free survival was significantly lower in the nontreatment group (P &lt; 0.01). In multivariate Cox regression analysis, thyroid hormone replacement therapy was found to be an independent predictor of renal outcome (hazard ratio, 0.28; 95% CI, 0.12–0.68; P = 0.01).

Conclusion:
Thyroid hormone therapy not only preserved renal function better, but was also an independent predictor of renal outcome in chronic kidney disease patients with subclinical hypothyroidism.
Linking Magnetic Clusters: Ferrimagnetic Interactions in a Nonanuclear Nickel(II) Cluster
Authors: Iijima Fumichika , Hasumi Koen , Shiga Takuya , Newton Graham N , Oshio Hiroki 
Published: June 2012

Abstract
A nonanuclear nickel(II) cluster, [Ni9(H4L)2(OMe)6(OAc)10(H2O)4]·14H2O (1·14H2O), was synthesized by the reaction of an amide ligand H5L (= 2-hydroxy-4,6-dimethyl-N1,N3-bis(2-hydroxyethyl)-1,3-benzenedicarboxamide) with nickel acetate in the presence of triethylamine. The cluster molecule consists of two cubane units and a mononuclear central moiety, connected by acetate bridges. In the cubane cores, ferromagnetic interactions between nickel ions were operative, and the total spin ground state was S = 7 due to ferrimagnetic interactions between the two ferromagnetic cubane cores and the mononuclear nickel spacer.
How Does Methanol Assist the Hydrogen Transfer in Pd-catalyzed Cyclocarbonylation of Allylic Alcohols? Insights from a DFT Study
Authors: Hassan Mawia , Zhang Xin , Zhang Wenchao , Guo Xiaojia , Chen Biaohua , Lei Ming 
Published: June 2012

Abstract
The carbonylation mechanisms of allylic alcohol catalyzed by [PdHCl(bppm)] complex were studied using a density functional theory (DFT) method. The results indicate that the catalytic cycle consists of three main steps: alkene insertion, CO insertion, and hydrogen transfer and product elimination. Pathways with a Pd(II) character are more favorable than that with Pd(IV) character. Methanol serves as the proton shuttle in carbonylation and reduces the energy barrier by 15.4 kcal mol−1 below that without methanol assistance.
Charge Transfer at the Interfaces between Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) (PEDOT:PSS) and Pentacene as Investigated by ESR
Authors: Ito Masaaki , Marumoto Kazuhiro 
Published: June 2012

Abstract
Electron spin resonance (ESR) study was performed on organic layered films of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/pentacene that were fabricated with different deposition speed of pentacene on PEDOT:PSS in order to investigate charge formation at the PEDOT:PSS/pentacene interfaces. Clear increases in ESR signals of not only pentacene but also PEDOT were observed, which are caused by the charge transfer at the interfaces. The charge transfer is prominent at high deposition speed of pentacene, which means that slow deposition speed is suitable for solar-cell fabrication without charge formation.
Improvement of Thermal Stability of Gold Nanoparticles by Synergistic Interligand Interactions
Authors: Okumura Atsushi , Tsuchido Yoshitaka , Yamada Kou , Todori Kenji , Machida Shigeru 
Published: June 2012

Abstract
Three types of novel gold nanoparticles containing a different condensed ring in their ligands were prepared. Their thermal stability was found to be much higher than that of typical gold nanoparticles surrounded by long-chain alkanethiols because of strong interligand interaction formed by the condensed rings (π–π stacking). A clear correlation was found between the thermal stability and the strength of π–π stacking.