bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Noncanonically Transcribed Subgenomic mRNA of Infectious Bronchitis Virus and Other Gammacoronaviruses
Authors: Bentley Kirsten , Keep Sarah May , Armesto Maria , Britton Paul 
Published: December 2012

ABSTRACT

Coronavirus subgenomic mRNA (sgmRNA) synthesis occurs via a process of discontinuous transcription involving transcription regulatory sequences (TRSs) located in the 5′ leader sequence (TRS-L) and upstream of each structural and group-specific gene (TRS-B). Several gammacoronaviruses including infectious bronchitis virus (IBV) contain a putative open reading frame (ORF), localized between the M gene and gene 5, which is controversial due to the perceived absence of a TRS. We have studied the transcription of a novel sgmRNA associated with this potential ORF and found it to be transcribed via a previously unidentified noncanonical TRS-B. Using an IBV reverse genetics system, we demonstrated that the template-switching event during intergenic region (IR) sgmRNA synthesis occurs at the 5′ end of the noncanonical TRS-B and recombines between nucleotides 5 and 6 of the 8-nucleotide consensus TRS-L. Introduction of a complete TRS-B showed that higher transcription levels are achieved by increasing the number of nucleotide matches between TRS-L and TRS-B. Translation of a protein from the sgmRNA was demonstrated using enhanced green fluorescent protein, suggesting the translation of a fifth, novel, group-specific protein for IBV. This study has resolved an issue concerning the number of ORFs expressed by members of the
Gammacoronavirus
genus and proposes the existence of a fifth IBV accessory protein. We confirmed previous reports that coronaviruses can produce sgmRNAs from noncanonical TRS-Bs, which may expand their repertoire of proteins. We also demonstrated that noncanonical TRS-Bs may provide a mechanism by which coronaviruses can control protein expression levels by reducing sgmRNA synthesis.
Childlessness, parental mortality and psychiatric illness: a natural experiment based on in vitro fertility treatment and adoption
Authors: Agerbo Esben , Mortensen Preben Bo , Munk-Olsen Trine 
Published: December 2012

BackgroundChildlessness increases the risk of premature mortality and psychiatric illness. These results might, however, be confounded by factors that affect both the chance of parenthood as well as the risk of premature death and psychiatric illness.MethodsUsing population-based health and social registers, we conducted a follow-up study of 21 276 childless couples in in vitro fertility treatment.ResultsThe crude death rate ratio in women who become mothers to a biological child is 0.25 (95% CI 0.16 to 0.39). In other words, childless women experience a fourfold higher rate of death, that is, 4.02 (2.56 to 6.31). The analogous death rate in fathers is approximately halved: 0.51 (0.39 to 0.68) and 0.55 (0.32 to 0.96) associated with having a biological child and an adopted child, respectively. With substance use disorders being the exception, none of the crude rates of psychiatric illness in parents of a biological child were statistically distinguishable from the rates in the childless. These findings were slightly confounded by age, calendar year, income, education, somatic comorbidity and marital breakup.ConclusionsMindful that association is not causation, our results suggest that the mortality rates are higher in the childless. Rates of psychiatric illness do not appear to vary with childlessness, but the rate of psychiatric illness in parents who adopt is decreased.
Proinflammatory Homeobox Gene, ISX, Regulates Tumor Growth and Survival in Hepatocellular Carcinoma
Authors: Hsu Shih-Hsien , Wang Li-Ting , Lee King-Teh , Chen Yao-Li , Liu Kwei-Yan , Suen Jau-Ling , Chai Chee-Yin , Wang Shen-Nien 
Published: December 2012

Abstract
Chronic inflammation drives initiation of hepatocellular carcinoma (HCC), but the underlying mechanisms linking inflammation and tumor formation remain obscure. In this study, we compared the expression of interleukin (IL)-6 and cyclin D1 (CCND1) with the IL-6–induced homeobox gene ISX (intestine-specific homeobox) in 119 paired specimens of HCCs and adjacent normal tissues and also in paired specimens from 11 patients with non-HCCs. In pathologic analysis, ISX exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number, and progression stage. Enforced expression of ISX accelerated cell proliferation and tumorigenic activity in hepatoma cells through CCND1 induction. In contrast, short hairpin RNA–mediated attenuation of ISX in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. A high positive correlation existed in human hepatoma tumors between ISX and CCND1 expression. Together, our results highlight ISX as an important regulator in hepatoma progression with significant potential as a prognostic and therapeutic target in HCCs. Cancer Res; 73(2); 508–18. ©2012 AACR.
Dual Blockade of HER2 in HER2-Overexpressing Tumor Cells Does Not Completely Eliminate HER3 Function
Authors: Garrett Joan T. , Sutton Cammie R. , Kuba María Gabriela , Cook Rebecca S. , Arteaga Carlos L. 
Published: December 2012

Abstract
Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 which, in turn, counteracts the antitumor action of the HER2-directed therapies. We hypothesized that suppression of HER3 would synergize with dual blockade of HER2 in breast cancer cells sensitive and refractory to HER2 antagonists.
Experimental Design: Inhibition of HER2/HER3 in HER2+ breast cancer cell lines was evaluated by Western blotting. We analyzed drug-induced apoptosis and two- and three-dimensional growth in vitro. Growth inhibition of PI3K was examined in vivo in xenografts treated with combinations of trastuzumab, lapatinib, and the HER3-neutralizing monoclonal antibody U3-1287.
Results: Treatment with U3-1287 blocked the upregulation of total and phosphorylated HER3 that followed treatment with lapatinib and trastuzumab and, in turn, enhanced the antitumor action of the combination against trastuzumab-sensitive and -resistant cells. Mice bearing HER2+ xenografts treated with lapatinib, trastuzumab, and U3-1287 exhibited fewer recurrences and better survival than mice treated with lapatinib and trastuzumab.
Conclusions: Dual blockade of HER2 with trastuzumab and lapatinib does not eliminate the compensatory upregulation of HER3. Therapeutic inhibitors of HER3 should be considered as part of multidrug combinations aimed at completely and rapidly disabling the HER2 network in HER2-overexpressing breast cancers. Clin Cancer Res; 19(3); 610–9. ©2012 AACR.
CREB-Binding Protein Regulates Ku70 Acetylation in Response to Ionization Radiation in Neuroblastoma
Authors: Subramanian Chitra , Hada Manila , Opipari Anthony W. , Castle Valerie P. , Kwok Roland P.S. 
Published: December 2012

Abstract
Ku70 was originally described as an autoantigen, but it also functions as a DNA repair protein in the nucleus and as an antiapoptotic protein by binding to Bax in the cytoplasm, blocking Bax-mediated cell death. In neuroblastoma (NB) cells, Ku70′s binding with Bax is regulated by Ku70 acetylation such that increasing Ku70 acetylation results in Bax release, triggering cell death. Although regulating cytoplasmic Ku70 acetylation is important for cell survival, the role of nuclear Ku70 acetylation in DNA repair is unclear. Here, we showed that Ku70 acetylation in the nucleus is regulated by the CREB-binding protein (CBP), and that Ku70 acetylation plays an important role in DNA repair in NB cells. We treated NB cells with ionization radiation and measured DNA repair activity as well as Ku70 acetylation status. Cytoplasmic and nuclear Ku70 were acetylated after ionization radiation in NB cells. Interestingly, cytoplasmic Ku70 was redistributed to the nucleus following irradiation. Depleting CBP in NB cells results in reducing Ku70 acetylation and enhancing DNA repair activity in NB cells, suggesting nuclear Ku70 acetylation may have an inhibitory role in DNA repair. These results provide support for the hypothesis that enhancing Ku70 acetylation, through deacetylase inhibition, may potentiate the effect of ionization radiation in NB cells. Mol Cancer Res; 11(2); 173–81. ©2012 AACR.
Talking while Chewing: Speaker Response to Natural Perturbation of Speech
Authors: Mayer Connor , Gick Bryan 
Published: December 2012

Abstract
This study looks at how the conflicting goals of chewing and speech production are reconciled by examining the acoustic and articulatory output of talking while chewing. We consider chewing to be a type of perturbation with regard to speech production, but with some important differences. Ultrasound and acoustic measurements were made while participants chewed gum and produced various utterances containing the sounds /s/, /ʃ/, and /r/. Results show a great deal of individual variation in articulation and acoustics between speakers, but consistent productions and maintenance of relative acoustic distances within speakers. Although chewing interfered with speech production, and this interference manifested itself in a variety of ways across speakers, the objectives of speech production were indirectly achieved within the constraints and variability introduced by individual chewing strategies.
Weakening of Intervocalic /s/ in the Nijmegen Corpus of Casual Spanish
Authors: Torreira Francisco , Ernestus Mirjam 
Published: December 2012

Abstract
This study describes the weakening of intervocalic /s/ in the Nijmegen Corpus of Casual Spanish and investigates the role of several potential conditioning factors, including morphological, lexical and probabilistic variables. Three acoustic parameters were examined: voicing, the difference in high-band (4–8 kHz) intensity between /s/ and the following vowel, and the duration of the dip in low-band (0–1.5 kHz) intensity in /s/. Over a third of the /s/ consonants exhibited uninterrupted voicing. All three parameters were highly sensitive to speech rate and, less consistently, to prosodic factors such as word position and stress. We also found that /s/ suffixes in redundant morphosyntactic contexts were more prone to weakening than other word-final /s/ segments. Several high-frequency words were particularly prone to weakening, but no general probabilistic effects were observed for factors claimed to favor reduction such as word frequency, contextual predictability or grammatical class. These findings demonstrate the complex variability characteristic of reduction phenomena in spontaneous speech.
Dialectal Differences in Spanish Voiced Obstruent Allophony: Costa Rican versus Iberian Spanish
Authors: Carrasco Patricio , Hualde José I. , Simonet Miquel 
Published: December 2012

Abstract
The Spanish voiced obstruents /b d g/ are traditionally described as having each two allophones: stop and fricative (approximant) in complementary distribution. Several researchers have noted that some Central American and Highland Colombian varieties deviate from the general allophonic distribution in showing a preference for stop realizations in all contexts, except for the intervocalic position. In this paper we report on a large-scale acoustic investigation of /b d g/ in postconsonantal (after a liquid, sibilant or glide) and postvocalic (after /a/) contexts in Costa Rica Spanish, establishing a comparison with the variety of Madrid, Spain, which we take as representative of a variety with the general pattern of allophony. Our study, based on a continuous measurement of intensity, confirms previous descriptions in that Costa Rica Spanish does indeed show a different pattern of allophony from that found in the Madrid variety. The analysis shows that in Costa Rica Spanish postconsonantal realizations of /b/ and /d/ are very different from postvocalic ones, with a clear separation in the degree of constriction between these two contexts. In Madrid, on the other hand, we find a continuum of constriction degrees, depending on the nature of the specific preceding segment, and without a clear separation between postvocalic and postconsonantal realizations. The question that naturally arises is that of the historical connection between these two patterns of allophony, for which we offer some speculation, based in historical parallels and comparison with other varieties.
Prospective Comparison of Valve Regurgitation Quantitation by Cardiac Magnetic Resonance Imaging and Transthoracic Echocardiography
Authors: Cawley Peter J. , Hamilton-Craig Christian , Owens David S. , Krieger Eric V. , Strugnell Wendy E. , Mitsumori Lee , D’Jang Caryn L. , Schwaegler Rebecca G. , Nguyen Khanh Q. , Nguyen Bianca , Maki Jeffrey H. , Otto Catherine M. 
Published: December 2012

Background—
Both transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging allow quantification of chronic aortic regurgitation (AR) and mitral regurgitation (MR). We hypothesized that CMR measurement of regurgitant volume (RVol) is more reproducible than TTE.

Methods and Results—

TTE and CMR performed on the same day in 57 prospectively enrolled adults (31 with AR, 26 with MR) were measured by 2 independent physicians. TTE RVol
AR
was calculated as Doppler left ventricular outflow minus inflow stroke volume. RVol
MR
was calculated by both the proximal isovelocity surface area method and Doppler volume flow at 2 sites. CMR RVol
AR
was calculated by phase-contrast velocity mapping at the aortic sinuses and RVol
MR
as total left ventricular minus forward stroke volume. Intraobserver and interobserver variabilities were similar. For AR, the Bland–Altman mean interobserver difference in RVol was −0.7 mL (95% confidence interval [CI], −5 to 4) for CMR and −9 mL (95% CI, −53 to −36) for TTE. The Pearson correlation was higher (
P
=0.001) between CMR (0.99) than TTE readers (0.89). For MR, the Bland–Altman mean difference in RVol between observers was −4 mL (95% CI, −21 to 13) for CMR compared with 0.7 mL (95% CI, −30 to 32) for the proximal isovelocity surface area and −10 mL (95% CI, −76 to 56) for TTE volume flow at 2 sites. Correlation was similar for CMR (0.94) versus TTE readers (0.90 for the proximal isovelocity surface area).

Conclusions—

Compared with TTE, CMR has lower intraobserver and interobserver variabilities for RVol
AR
, suggesting CMR may be superior for serial measurements. Although RVol
MR
is similar by TTE and CMR, variability in measured RVol by both approaches suggests that caution is needed in clinical practice.
Detection and Grading of Coronary Allograft Vasculopathy in Children With Contrast-Enhanced Magnetic Resonance Imaging of the Coronary Vessel Wall
Authors: Hussain Tarique , Fenton Matthew , Peel Sarah A. , Wiethoff Andrea J. , Taylor Andrew , Muthurangu Vivek , Razavi Reza , Botnar Rene M. , Burch Michael , Greil Gerald F. 
Published: December 2012

Background—
Coronary allograft vasculopathy is the leading cause of late death after heart transplantation in children. It is poorly detected by conventional angiography. Intravascular ultrasound is invasive and costly. This study shows that magnetic resonance imaging (MRI) late gadolinium enhancement (LGE) of the coronary vessel wall can detect and grade coronary allograft vasculopathy.

Methods and Results—

Twenty-four children (10 male; age range, 9–17 years) underwent coronary angiography, intravascular ultrasound, and MRI. Maximal intimal thickness and mean intimal index were recorded. MRI included coronary magnetic resonance angiogram and LGE vessel wall imaging with 1.5 T (n=12) and 3.0 T (n=12). Ten healthy control subjects also underwent LGE MRI. Mean time posttransplantation was 5.5 years (range, 0.25–14 years). Seven patients had Stanford grade IV coronary allograft vasculopathy on intravascular ultrasound, 3 of whom had angiographic disease. Maximal intimal thickness and mean intimal index were 0.73±0.50 mm and 20.9±10.6%, respectively. On MRI, mean diameter of enhancement of vessel wall was 6.57±4.91 mm, and mean enhancement index (indexed to vessel lumen size) was 1.10±1.72. The control group showed little or no LGE. Correlation of LGE with maximal intimal thickness using the Pearson coefficient was 0.80 (
P
<0.001) and with mean intimal index was 0.92 (
P
<0.001). An MRI diameter >7.5 mm gave 86% sensitivity and 93% specificity.

Conclusions—
LGE scores correlate well with traditional intravascular ultrasound measures. These promising early results encourage larger-scale clinical studies to investigate whether LGE MRI will allow closer follow-up and better prevention of coronary allograft vasculopathy in children.
A Simple Framework for the Dynamic Response of Cirrus Clouds to Local Diabatic Radiative Heating
Authors: Schmidt Clinton T. , Garrett Timothy J. 
Published: December 2012

Abstract
This paper presents a simple analytical framework for the dynamic response of cirrus to a local radiative flux convergence, expressible in terms of three independent modes of cloud evolution. Horizontally narrow and tenuous clouds within a stable environment adjust to radiative heating by ascending gradually across isentropes while spreading sufficiently fast that isentropic surfaces stay nearly flat. Alternatively, optically dense clouds experience very concentrated heating, and if they are also very broad, they develop a convecting mixed layer. Along-isentropic spreading still occurs, but in the form of turbulent density currents rather than laminar flows. A third adjustment mode relates to evaporation, which erodes cloudy air as it lofts, regardless of its optical density. The dominant mode is determined from two dimensionless numbers, whose predictive power is shown in comparisons with high-resolution numerical cloud simulations. The power and simplicity of the approach hints that fast, subgrid-scale radiative–dynamic atmospheric interactions might be efficiently parameterized within slower, coarse-grid climate models.
Genesis of the South Asian High and Its Impact on the Asian Summer Monsoon Onset
Authors: Liu Boqi , Wu Guoxiong , Mao Jiangyu , He Jinhai 
Published: December 2012

AbstractThe formation of the South Asian high (SAH) in spring and its impacts on the Asian summer monsoon onset are studied using daily 40-yr ECMWF Re-Analysis (ERA-40) data together with a climate-mean composite technique and potential vorticity–diabatic heating (PV–Q) analysis. Results demonstrate that, about 2 weeks before the Asian summer monsoon onset, a burst of convection over the southern Philippines produces a negative vorticity source to its north. The SAH in the upper troposphere over the South China Sea is then generated as an atmospheric response to this negative vorticity forcing with the streamline field manifesting a Gill-type pattern. Afterward, the persistent rainfall over the northern Indochinese peninsula causes the SAH to move westward toward the peninsula. Consequently, a trumpet-shaped flow field is formed to its southwest, resulting in divergence pumping and atmospheric ascent just over the southeastern Bay of Bengal (BOB).Near the surface, as a surface anticyclone is formed over the northern BOB, an SST warm pool is generated in the central–eastern BOB. This, together with SAH pumping, triggers the formation of a monsoon onset vortex (MOV) with strong surface southwesterly developed over the BOB. Enhanced air–sea interaction promotes the further development and northward migration of the MOV. Consequently, the wintertime zonal-orientated subtropical anticyclone belt in the lower troposphere splits, abundant water vapor is transported directly from the BOB to the subtropical continent, and heavy rainfall ensues; the atmospheric circulation changes from winter to summer conditions over the BOB and Asian summer monsoon onset occurs.
Investigating Variability of Outgoing Longwave Radiation over Peninsular Malaysia Using Wavelet Transform
Authors: Lim E. S. , Das Uma , Pan C. J. , Abdullah K. , Wong C. J. 
Published: December 2012

Abstract
The present study analyzes and quantifies the spatial–temporal variability of outgoing longwave radiation (OLR) over peninsular Malaysia using the continuous wavelet transform (CWT) from 2003 to 2010. The goal is to understand the long-term variability of OLR over Malaysia in terms of time–frequency variations in relation to the monsoon period and other weather phenomena. The study regions selected were the west coast, east coast, and southern part of peninsular Malaysia. The OLR variation characteristics in time and space derived from wavelet transform were found to be distinctly different in these three regions. In these three regions, OLR showed significant periodicities dominated by the annual cycle, followed by a semiannual cycle. The west coast of peninsular Malaysia has a lower annual component compared to the other regions because of the rain-sheltering effect by the mountain range that blocked the heavy rainfall from northeast monsoon winds. Besides that, the results show that the wet and dry spells coincide with local monsoon and intermonsoon periods. Meanwhile, the results also revealed that the semiannual variation is statistically significant during 2004–06. The strong semiannual variation is coincident with several droughts that resulted from the strong El Niño events in 2004–06. In addition, the phase plot of wavelet coefficients shows that the variations at various scales are in phase, which coincided with the sudden variations of OLR, indicating heavy flood occurrences in the southern part of peninsular Malaysia. The results show that CWT is a powerful tool for analysis of phenomena involving multiscale interactions that exhibit localization in both time and frequency.
Effects of Stochastic Ice Strength Perturbation on Arctic Finite Element Sea Ice Modeling
Authors: Juricke Stephan , Lemke Peter , Timmermann Ralph , Rackow Thomas 
Published: December 2012

Abstract
The ice strength parameter P* is a key parameter in dynamic/thermodynamic sea ice models that cannot be measured directly. Stochastically perturbing P* in the Finite Element Sea Ice–Ocean Model (FESOM) of the Alfred Wegener Institute aims at investigating the effect of uncertainty pertaining to this parameterization. Three different approaches using symmetric perturbations have been applied: 1) reassignment of uncorrelated noise fields to perturb P* at every grid point, 2) a Markov chain time correlation, and 3) a Markov chain time correlation with some spatial correlation between nodes. Despite symmetric perturbations, results show an increase of Arctic sea ice volume and a decrease of Arctic sea ice area for all three approaches. In particular, the introduction of spatial correlation leads to a substantial increase in sea ice volume and mean thickness. The strongest response can be seen for multiyear ice north of the Greenland coast. An ensemble of eight perturbed simulations generates a spread in the multiyear ice comparable to the interannual variability of the model. Results cannot be reproduced by a simple constant global modification of P*.