bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone Methyltransferase hSETD1A Is a Novel Regulator of Metastasis in Breast Cancer
Authors: Salz Tal , Deng Changwang , Pampo Christine , Siemann Dietmar , Qiu Yi , Brown Kevin , Huang Suming 
Published: November 2014

Abstract
Epigenetic alteration is a hallmark of all cancers. Such alterations lead to modulation of fundamental cancer-related functions, such as proliferation, migration, and invasion. In particular, methylation of Histone H3 Lysine 4 (H3K4), a histone mark generally associated with transcriptional activation, is altered during progression of several human cancers. While the depletion of H3K4 demethylases promotes breast cancer metastasis, the effect of H3K4 methyltransferases on metastasis is not clear. Nevertheless, gene duplications in the human SETD1A (hSETD1A) H3K4 methyltransferase are present in almost half of breast cancers. Herein, expression analysis determined that hSETD1A is upregulated in multiple metastatic human breast cancer cell lines and clinical tumor specimens. Ablation of hSETD1A in breast cancer cells led to a decrease in migration and invasion in vitro and to a decrease in metastasis in nude mice. Furthermore, a group of matrix metalloproteinases (including MMP2, MMP9, MMP12, MMP13, and MMP17) were identified which were downregulated upon depletion of hSETD1A and demonstrated a decrease in H3K4me3 at their proximal promoters based on chromatin immunoprecipitation analysis. These results provide evidence for a functional and mechanistic link among hSETD1A, MMPs, and metastasis in breast cancer, thereby supporting an oncogenic role for hSETD1A in cancer.
Implications: This study reveals that hSETD1A controls tumor metastasis by activating MMP expression and provides an epigenetic link among hSETD1A, MMPs, and metastasis of breast cancer. Mol Cancer Res; 13(3); 461–9. ©2014 AACR.
PD-L1 Expression in Melanocytic Lesions Does Not Correlate with the BRAF V600E Mutation
Authors: Rodić Nemanja , Anders Robert A. , Eshleman James R. , Lin Ming-Tseh , Xu Haiying , Kim Jung H. , Beierl Katie , Chen Shuming , Luber Brandon S. , Wang Hao , Topalian Suzanne L , Pardoll Drew M. , Taube Janis M. 
Published: November 2014

Abstract
PD-L1 expression in melanoma correlates with response to PD-1 pathway–blocking antibodies. Aberrant tumor-cell PD-L1 expression may be oncogene driven and/or induced by IFNγ. Melanomas express PD-L1 in association with tumor-infiltrating lymphocytes (TIL), but the potential contribution of the BRAF V600E mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two archival melanocytic lesions were assessed for PD-L1 expression, TIL infiltration, and BRAFmut simultaneously. IFNγ-induced PD-L1 expression in cultured melanomas was assessed in parallel according to BRAF status. Melanocyte PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in 42% of specimens, but no significant concordance was found between these variables. Almost all melanocytes displaying PD-L1 expression were observed to be adjacent to TILs, irrespective of BRAF status. TIL− lesions were not more likely to be associated with BRAFmut, when compared with TIL+ lesions. Baseline expression of PD-L1 by melanoma cell lines was virtually nil, regardless of BRAFmut status, and the intensity of IFN-induced PD-L1 expression in melanoma cell lines likewise did not correlate with BRAF mutational status. PD-L1 expression in melanocytic lesions does not correlate with the BRAFmut. Thus, distinct populations of melanoma patients will likely benefit from BRAF inhibitors versus PD-1 pathway blockade. Cancer Immunol Res; 3(2); 110–5. ©2014 AACR.
α1-A680T Variant in GUCY1A3 as a Candidate Conferring Protection From Pulmonary Hypertension Among Kyrgyz Highlanders
Authors: Wilkins Martin R. , Aldashev Almaz A. , Wharton John , Rhodes Christopher J. , Vandrovcova Jana , Kasperaviciute Dalia , Bhosle Shriram G. , Mueller Michael , Geschka Sandra , Rison Stuart , Kojonazarov Baktybek , Morrell Nicholas W. , Neidhardt Inga , Surmeli Nur Basak , Aitman Tim J. , Stasch Johannes-Peter , Behrends Soenke , Marletta Michael A. 
Published: November 2014

Background—
Human variation in susceptibility to hypoxia-induced pulmonary hypertension is well recognized. High-altitude residents who do not develop pulmonary hypertension may host protective gene mutations.

Methods and Results—

Exome sequencing was conducted on 24 unrelated Kyrgyz highlanders living 2400 to 3800 m above sea level, 12 (10 men; mean age, 54 years) with an elevated mean pulmonary artery pressure (mean±SD, 38.7±2.7 mm Hg) and 12 (11 men; mean age, 52 years) with a normal mean pulmonary artery pressure (19.2±0.6 mm Hg) to identify candidate genes that may influence the pulmonary vascular response to hypoxia. A total of 140 789 exomic variants were identified and 26 116 (18.5%) were classified as novel or rare. Thirty-three novel or rare potential pathogenic variants (frameshift, essential splice-site, and nonsynonymous) were found exclusively in either ≥3 subjects with high-altitude pulmonary hypertension or ≥3 highlanders with a normal mean pulmonary artery pressure. A novel missense mutation in
GUCY1A3
in 3 subjects with a normal mean pulmonary artery pressure encodes an α
1
-A680T soluble guanylate cyclase (sGC) variant. Expression of the α
1
-A680T sGC variant in reporter cells resulted in higher cyclic guanosine monophosphate production compared with the wild-type enzyme and the purified α
1
-A680T sGC exhibited enhanced sensitivity to nitric oxide in vitro.

Conclusions—

The α
1
-A680T sGC variant may contribute to protection against high-altitude pulmonary hypertension and supports sGC as a pharmacological target for reducing pulmonary artery pressure in humans at altitude.
In Vivo Imaging of the Mouse Neurovascular Unit Under Chronic Cerebral Hypoperfusion
Authors: Yata Kenichiro , Nishimura Yuhei , Unekawa Miyuki , Tomita Yutaka , Suzuki Norihiro , Tanaka Toshio , Mizoguchi Akira , Tomimoto Hidekazu 
Published: November 2014

Background and Purpose—
Proper brain function is maintained by an integrated system called the neurovascular unit (NVU) comprised cellular and acellular elements. Although the individual features of specific neurovascular components are understood, it is unknown how they respond to ischemic stress as a functional unit. Therefore, we established an in vivo imaging method and clarified the NVU response to chronic cerebral hypoperfusion.

Methods—
Green mice (b-act-EGFP) with SR101 plasma labeling were used in this experiment. A closed cranial window was made over the left somatosensory cortex. To mimic chronic cerebral hypoperfusion, mice were subjected to bilateral common carotid artery stenosis operations using microcoils. In vivo real-time imaging was performed using 2-photon laser-scanning microscopy during the preoperative period, and after 1 day and 1 and 2 weeks of bilateral common carotid artery stenosis or sham operations.

Results—
Our method allowed 3-dimensional observation of most of the components of the NVU, as well as dynamic capillary microcirculation. Under chronic cerebral hypoperfusion, we did not detect any structural changes of each cellular component in the NVU; however, impairment of microcirculation was detected over a prolonged period. In the pial small arteries and veins, rolling and adhesion of leukocyte were detected, more prominently in the latter. In the deep cortical capillaries, flow stagnation because of leukocyte plugging was frequently observed.

Conclusions—
We established an in vivo imaging method for real-time visualization of the NVU. It seems that under chronic cerebral hypoperfusion, leukocyte activation has a critical role in microcirculation disturbance.
Quantitative Measurement of Physical Activity in Acute Ischemic Stroke and Transient Ischemic Attack
Authors: Strømmen Anna Maria , Christensen Thomas , Jensen Kai 
Published: November 2014

Background and Purpose—
The purpose of this study was to quantitatively measure and describe the amount and pattern of physical activity in patients within the first week after acute ischemic stroke and transient ischemic attack using accelerometers.

Methods—
A total of 100 patients with acute ischemic stroke or transient ischemic attack admitted to our acute stroke unit wore Actical accelerometers attached to both wrists and ankles and the hip for ≤7 days. Patients were included within 72 hours of symptom onset. Accelerometer output was measured in activity counts (AC). Patients were tested daily with Scandinavian Stroke Scale.

Results—
Physical activity peaked in the morning and declined during the rest of the day. In patients with stroke, total AC were 71% lower than in patients with transient ischemic attack. AC were 80% lower in the paretic compared with those in the nonparetic arm in patients with ischemic stroke. For the legs AC were 44% lower on the paretic side and an overall increase in AC with time was found. There was a significant increase in AC with increasing Scandinavian Stroke Scale and a decrease in AC with increasing age.

Conclusions—
This study demonstrates the feasibility of using accelerometers to quantitatively and continuously measure physical activity simultaneously from all 4 extremities and the hip in patients with acute ischemic stroke and transient ischemic attack. Our study provides quantitative evidence of physical inactivity in patients with acute ischemic stroke. The method offers a low cost and noninvasive tool for future clinical interventional physiotherapeutic and early mobilization studies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01560520.
Frequency and Predictors of Stroke After Acute Myocardial Infarction
Authors: Hachet Olivier , Guenancia Charles , Stamboul Karim , Daubail Benoit , Richard Carole , Béjot Yannick , Yameogo Valentin , Gudjoncik Aurélie , Cottin Yves , Giroud Maurice , Lorgis Luc 
Published: November 2014

Background and Purpose—
Stroke is a serious complication after acute myocardial infarction (AMI) and is closely associated with decreased survival. This study aimed to investigate the frequency, characteristics, and factors associated with in-hospital and postdischarge stroke in patients with AMI.

Methods—
Eight thousand four hundred eighty-five consecutive patients admitted to a cardiology intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient ischemic attack were collected during 1-year follow-up.

Results—
One hundred twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first day after admission for AMI, and 108 (87%) within the first 5 days. One hundred six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in-hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed that only 2 types of stroke were identified more frequently. As expected, the leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64, 60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After multivariable backward regression analysis, female sex, previous transient ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular ejection fraction (odds ratio per point of left ventricular ejection fraction), and C-reactive protein were independently associated with in-hospital ischemic stroke. When antiplatelet and anticoagulation therapy within the first 48 hours was introduced into the multivariable model, we found that implementing these treatments (≥1) was an independent protective factor of in-hospital stroke. In-hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis was prescribed as the reperfusion treatment. However, the different parenteral anticoagulants were not predictors of risk in univariable analysis. Finally, only 45 postdischarge strokes were recorded. Postdischarge stroke subtypes showed a more heterogeneous distribution of mechanisms. The annual rate of stroke post-AMI remained stable throughout the 10-year study period.

Conclusions—
The present study describes specific predictors of in-hospital and postdischarge stroke in patients with AMI. It showed a marked increase in the risk of death, both during hospitalization and in the year after AMI. After hospital discharge, stroke remains a rare event and is mostly associated with high cardiovascular risk.
White Matter Edema at the Early Stage of Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: De Guio François , Mangin Jean-François , Duering Marco , Ropele Stefan , Chabriat Hugues , Jouvent Eric 
Published: November 2014

Background and Purpose—
Recently, in a mouse model of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a monogenic cerebral small vessel disease, intramyelinic edema was detected in the white matter (WM) early during the course of the disease. We hypothesized that if this mechanism holds true in patients, it would translate in larger WM volume. We aimed to measure WM volume in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy in comparison with age- and sex-matched controls, along with the ratio of cortical surface area to the volume of brain hemispheres as an indirect measure that should be reduced in patients.

Methods—
Twenty patients at the early stage of the disease (Mini Mental State Examination >24 and modified Rankin scale ≤1) and 27 age- and sex-matched controls had high-quality 3-Tesla 3DT1 MRI acquisitions. Volumes of brain hemispheres and of WM were determined. The ratio of cortical surface area to the volume of brain hemispheres was evaluated as a proxy of underlying WM volume.

Results—

Patients had larger volumes of WM than controls (patients: 479.4±71.7; controls: 463.9±44.2;
P
=0.03). They presented a lower cortical surface area and cortical volume leading to a lower ratio of cortical surface area to the volume of brain hemispheres (patients: 15.7±0.7; controls: 16.1±0.5;
P
=0.004). Volume of WM tended to be associated with that of WM hyperintensities (
P
=0.06).

Conclusions—
Patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy have larger WM volume than age- and sex-matched controls, a finding compatible with the hypothesis of intramyelinic edema as observed recently in mice.
The Magic Jar and Other Devices from 9th Century Persia
Authors: Yassi Yousef 
Published: November 2014

After the advent of Islam the interest of scientists was drawn towards “ingenious devices.” Ahmad ibn Müsä ibn Shäkir Khuräsäni was one of the greatest Iranian scientists of the 9th century AD. He worked on many mechanical, hydraulic and pneumatic devices and presented his inventions in a book entitled Kitäb Al-Hiyal. A combined historical and experimental research project was undertaken by the Iranian Research Organization for Science and Technology (IROST). One part of the project consisted of designing and reproducing the mechanisms for separating liquids described in Al-Hiyal. This paper provides details of the design of four of these devices, which function on the basis of the relative viscosities or densities of the liquids being separated. They were recreated and tested in accordance with the indications provided in ibn Shäkir Khuräsäni’s text. This paper provides the historical background and a technical analysis of these remarkable inventions.
Extreme Rainfall of the South American Monsoon System: A Dataset Comparison Using Complex Networks
Authors: Boers Niklas , Bookhagen Bodo , Marengo José , Marwan Norbert , von Storch Jin-Song , Kurths Jürgen 
Published: November 2014

Abstract
In this study, the authors compare six different rainfall datasets for South America with a focus on their representation of extreme rainfall during the monsoon season (December–February): the gauge-calibrated TRMM 3B42 V7 satellite product; the near-real-time TRMM 3B42 V7 RT, the GPCP 1° daily (1DD) V1.2 satellite–gauge combination product, the Interim ECMWF Re-Analysis (ERA-Interim) product; output of a high-spatial-resolution run of the ECHAM6 global circulation model; and output of the regional climate model Eta. For the latter three, this study can be understood as a model evaluation. In addition to statistical values of local rainfall distributions, the authors focus on the spatial characteristics of extreme rainfall covariability. Since traditional approaches based on principal component analysis are not applicable in the context of extreme events, they apply and further develop methods based on complex network theory. This way, the authors uncover substantial differences in extreme rainfall patterns between the different datasets: (i) The three model-derived datasets yield very different results than the satellite–gauge combinations regarding the main climatological propagation pathways of extreme events as well as the main convergence zones of the monsoon system. (ii) Large discrepancies are found for the development of mesoscale convective systems in southeastern South America. (iii) Both TRMM datasets and ECHAM6 indicate a linkage of extreme rainfall events between the central Amazon basin and the eastern slopes of the central Andes, but this pattern is not reproduced by the remaining datasets. The authors’ study suggests that none of the three model-derived datasets adequately captures extreme rainfall patterns in South America.
Parameter Estimation Using Ensemble-Based Data Assimilation in the Presence of Model Error
Authors: Ruiz Juan , Pulido Manuel 
Published: November 2014

Abstract
This work explores the potential of online parameter estimation as a technique for model error treatment under an imperfect model scenario, in an ensemble-based data assimilation system, using a simple atmospheric general circulation model, and an observing system simulation experiment (OSSE) approach. Model error is introduced in the imperfect model scenario by changing the value of the parameters associated with different schemes. The parameters of the moist convection scheme are the only ones to be estimated in the data assimilation system. In this work, parameter estimation is compared and combined with techniques that account for the lack of ensemble spread and for the systematic model error. The OSSEs show that when parameter estimation is combined with model error treatment techniques, multiplicative and additive inflation or a bias correction technique, parameter estimation produces a further improvement of analysis quality and medium-range forecast skill with respect to the OSSEs with model error treatment techniques without parameter estimation. The improvement produced by parameter estimation is mainly a consequence of the optimization of the parameter values. The estimated parameters do not converge to the value used to generate the observations in the imperfect model scenario; however, the analysis error is reduced and the forecast skill is improved.
The Diurnal Cycle of Precipitation in Regional Spectral Model Simulations over West Africa: Sensitivities to Resolution and Cumulus Schemes
Authors: He Xiaogang , Kim Hyungjun , Kirstetter Pierre-Emmanuel , Yoshimura Kei , Chang Eun-Chul , Ferguson Craig R. , Erlingis Jessica M. , Hong Yang , Oki Taikan 
Published: November 2014

Abstract
As a basic form of climate patterns, the diurnal cycle of precipitation (DCP) can provide a key test bed for model reliability and development. In this study, the DCP over West Africa was simulated by the National Centers for Environmental Prediction (NCEP) Regional Spectral Model (RSM) during the monsoon season (April–September) of 2005. Three convective parameterization schemes (CPSs), single-layer simplified Arakawa–Schubert (SAS), multilayer relaxed Arakawa–Schubert (RAS), and new Kain–Fritsch (KF2), were evaluated at two horizontal resolutions (20 and 10 km). The Benin mesoscale site was singled out for additional investigation of resolution effects. Harmonic analysis was used to characterize the phase and amplitude of the DCP. Compared to satellite observations, the overall spatial distributions of amplitude were well captured at regional scales. The RSM properly reproduced the observed late afternoon peak over land and the early morning peak over ocean. Nevertheless, the peak time was early. Sensitivity experiments of CPSs showed similar spatial patterns of rainfall totals among the schemes; CPSs mainly affected the amplitude of the diurnal cycle, while the phase was not significantly shifted. There is no clear optimal pairing of resolution and CPS. However, it is found that the sensitivity of DCP to CPSs and resolution varies with the partitioning between convective and stratiform, which implies that appropriate partitioning needs to be considered for future development of CPSs in global or regional climate models.
Aging by moisture and/or temperature of epoxy/SiC composites: Thermal and mechanical properties
Authors: Abenojar Juana , Pantoja Mariola , Martínez Miguel Angel , del Real Juan Carlos 
Published: November 2014

The present work focuses on investigating the effects of moisture absorption on the mechanical and thermal properties of epoxy reinforced with percentage (by wt.) silicon carbide (nano and micro-metric) composites. In order to quantify the effect of moisture and temperature on aging, the specimens were exposed to three aging conditions for 30 days. Variations of Tg (glass transition temperature), water absorption, and mechanical properties were determined as a function of exposure time. In composite materials, aging depends on the exposure conditions, such as amount of absorbed water, temperature, and oxygen concentration. All these factors affect the thermal and mechanical properties. At room temperature and 95% relative humidity, plasticizing and swelling occur, with mechanical properties loss. At 60℃ and 5% relative humidity, polymeric chains crosslink resulting in mechanical properties improvement; Tg and thermal conductivity increase. At 60℃ and 95% relative humidity, the time required to reach saturation decreases when compared to room temperature evaluated condition, as the exposure temperature increases.