bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 Overexpression Renders Human Breast Cancers Sensitive to PARP Inhibition Independently of Any Defect in Homologous Recombination DNA Repair
Authors: Nowsheen Somaira , Cooper Tiffiny , Bonner James A. , LoBuglio Albert F. , Yang Eddy S. 
Published: September 2012

Abstract
HER2 overexpression in breast cancer confers increased tumor aggressiveness. Although anti-HER2 therapies have improved patient outcome, resistance ultimately occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we show that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR deficiency. HER2 overexpression in HER2 negative breast cancer cells was sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD-2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In addition, ABT-888 significantly inhibited NF-κB (p65/RelA) transcriptional activity in HER2+ but not HER2 negative breast cancer cells. This corresponded with a reduction in phosphorylated p65 and total IKKα levels, with a concomitant increase in IκBα. Overexpression of p65 abrogated cellular sensitivity to ABT-888, whereas IκBα overexpression reduced cell viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+ breast cancer cells to PARP inhibition may be because of inhibition of NF-κB signaling driven by HER2. Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2+ breast cancer patients. Cancer Res; 72(18); 4796–806. ©2012 AACR.
Interaction between the MJO and Polar Circulations
Authors: Flatau Maria , Kim Young-Joon 
Published: September 2012

Abstract
A tropical–polar connection and its seasonal dependence are examined using the real-time multivariate Madden–Julian oscillation (MJO) (RMM) index and daily indices for the annular modes, the Arctic Oscillation (AO) and the Antarctic Oscillation (AAO). On the intraseasonal time scale, the MJO appears to force the annular modes in both hemispheres. On this scale, during the cold season, the convection in the Indian Ocean precedes the increase of the AO/AAO. Interestingly, during the boreal winter (Southern Hemisphere warm season), strong MJOs in the Indian Ocean are related to a decrease of the AAO index, and AO/AAO tendencies are out of phase. On the longer time scales, a persistent AO/AAO anomaly appears to influence the convection in the tropical belt and impact the distribution of MJO-preferred phases. It is shown that this may be a result of the sea surface temperature (SST) changes related to a persistent AO, with cooling over the Indian Ocean and warming over Indonesia. In the Southern Hemisphere, the SST anomalies are to some extent also related to a persistent AAO pattern, but this relationship is much weaker and appears only during the Southern Hemisphere cold season. On the basis of these results, a mechanism involving the air–sea interaction in the tropics is suggested as a possible link between persistent AO and convective activity in the Indian Ocean and western Pacific.
Transient Climate Response in a Two-Layer Energy-Balance Model. Part II: Representation of the Efficacy of Deep-Ocean Heat Uptake and Validation for CMIP5 AOGCMs
Authors: Geoffroy O. , Saint-Martin D. , Bellon G. , Voldoire A. , Olivié D. J. L. , Tytéca S. 
Published: September 2012

AbstractIn this second part of a series of two articles analyzing the global thermal properties of atmosphere–ocean coupled general circulation models (AOGCMs) within the framework of a two-layer energy-balance model (EBM), the role of the efficacy of deep-ocean heat uptake is investigated. Taking into account such an efficacy factor is shown to amount to representing the effect of deep-ocean heat uptake on the local strength of the radiative feedback in the transient regime. It involves an additional term in the formulation of the radiative imbalance at the top of the atmosphere (TOA), which explains the nonlinearity between radiative imbalance and the mean surface temperature observed in some AOGCMs. An analytical solution of this system is given and this simple linear EBM is calibrated for the set of 16 AOGCMs of phase 5 of the Coupled Model Intercomparison Project (CMIP5) studied in Part I. It is shown that both the net radiative fluxes at TOA and the global surface temperature transient response are well represented by the simple EBM over the available period of simulations. Differences between this two-layer EBM and the previous version without an efficacy factor are analyzed and relationships between parameters are discussed. The simple model calibration applied to AOGCMs constitutes a new method for estimating their respective equilibrium climate sensitivity and adjusted radiative forcing amplitude from short-term step-forcing simulations and more generally a method to compute their global thermal properties.
The Life Cycle of Northern Hemisphere Downward Wave Coupling between the Stratosphere and Troposphere
Authors: Shaw Tiffany A. , Perlwitz Judith 
Published: September 2012

Abstract
The life cycle of Northern Hemisphere downward wave coupling between the stratosphere and troposphere via wave reflection is analyzed. Downward wave coupling events are defined by extreme negative values of a wave coupling index based on the leading principal component of the daily wave-1 heat flux at 30 hPa. The life cycle occurs over a 28-day period. In the stratosphere there is a transition from positive to negative total wave-1 heat flux and westward to eastward phase tilt with height of the wave-1 geopotential height field. In addition, the zonal-mean zonal wind in the upper stratosphere weakens leading to negative vertical shear.
Following the evolution in the stratosphere there is a shift toward the positive phase of the North Atlantic Oscillation (NAO) in the troposphere. The pattern develops from a large westward-propagating wave-1 anomaly in the high-latitude North Atlantic sector. The subsequent equatorward propagation leads to a positive anomaly in midlatitudes. The near-surface temperature and circulation anomalies are consistent with a positive NAO phase. The results suggest that wave reflection events can directly influence tropospheric weather.
Finally, winter seasons dominated by extreme wave coupling and stratospheric vortex events are compared. The largest impacts in the troposphere occur during the extreme negative seasons for both indices, namely seasons with multiple wave reflection events leading to a positive NAO phase or seasons with major sudden stratospheric warmings (weak vortex) leading to a negative NAO phase. The results reveal that the dynamical coupling between the stratosphere and NAO involves distinct dynamical mechanisms that can only be characterized by separate wave coupling and vortex indices.
Stress in adults with congenital deafblindness and an intellectual disability: Information from their cortisol curves
Authors: Bloeming-Wolbrink Kitty A , Janssen Marleen J , de Weerth Carolina , Ruijssenaars Wied AJJM , Sweep Fred CGJ , Eijsbouts Agnes , Riksen-Walraven J Marianne A 
Published: September 2012

Adults with congenital deafblindness and an intellectual disability are at high risk for exposure to chronic and severe stress. Sensory deprivation, separations from primary caregivers, and difficulties in communication, from birth on, make daily life stressful for them. Chronic and high stress can lead to deviancies in the cortisol curve. This, in turn, can have negative effects on mental and physical health. Nothing is known yet about the cortisol curve of adults with congenital deafblindness and an intellectual disability, but our hypothesis is that it will be deviant. In this study, the cortisol curve of six participants with congenital deafblindness was compared to the curve of 40 typical controls. Remarkably, in spite of all past and present stress factors, the cortisol curve of the participants was rather normal. Possible explanations for this finding are discussed, amongst others individual differences in experiencing stress. Implications for further research are discussed.
A pipeline for automated annotation of yeast genome sequences by a conserved-synteny approach
Authors: Proux-Wéra Estelle , Armisén David , Byrne Kevin P , Wolfe Kenneth H 
Published: September 2012

Abstract

Background
Yeasts are a model system for exploring eukaryotic genome evolution. Next-generation sequencing technologies are poised to vastly increase the number of yeast genome sequences, both from resequencing projects (population studies) and from de novo sequencing projects (new species). However, the annotation of genomes presents a major bottleneck for de novo projects, because it still relies on a process that is largely manual.

Results
Here we present the Yeast Genome Annotation Pipeline (YGAP), an automated system designed specifically for new yeast genome sequences lacking transcriptome data. YGAP does automatic de novo annotation, exploiting homology and synteny information from other yeast species stored in the Yeast Gene Order Browser (YGOB) database. The basic premises underlying YGAP's approach are that data from other species already tells us what genes we should expect to find in any particular genomic region and that we should also expect that orthologous genes are likely to have similar intron/exon structures. Additionally, it is able to detect probable frameshift sequencing errors and can propose corrections for them. YGAP searches intelligently for introns, and detects tRNA genes and Ty-like elements.

Conclusions
In tests on Saccharomyces cerevisiae and on the genomes of Naumovozyma castellii and Tetrapisispora blattae newly sequenced with Roche-454 technology, YGAP outperformed another popular annotation program (AUGUSTUS). For S. cerevisiae and N. castellii, 91-93% of YGAP's predicted gene structures were identical to those in previous manually curated gene sets. YGAP has been implemented as a webserver with a user-friendly interface athttp://wolfe.gen.tcd.ie/annotation.
The Drosophila nicotinic acetylcholine receptor subunits Dα5 and Dα7 form functional homomeric and heteromeric ion channels
Authors: Lansdell Stuart J , Collins Toby , Goodchild Jim , Millar Neil S 
Published: September 2012

Abstract

Background
Nicotinic acetylcholine receptors (nAChRs) play an important role as excitatory neurotransmitters in vertebrate and invertebrate species. In insects, nAChRs are the site of action of commercially important insecticides and, as a consequence, there is considerable interest in examining their functional properties. However, problems have been encountered in the successful functional expression of insect nAChRs, although a number of strategies have been developed in an attempt to overcome such difficulties. Ten nAChR subunits have been identified in the model insect Drosophila melanogaster (Dα1-Dα7 and Dβ1-Dβ3) and a similar number have been identified in other insect species. The focus of the present study is the Dα5, Dα6 and Dα7 subunits, which are distinguished by their sequence similarity to one another and also by their close similarity to the vertebrate α7 nAChR subunit.

Results
A full-length cDNA clone encoding the Drosophila nAChR Dα5 subunit has been isolated and the properties of Dα5-, Dα6- and Dα7-containing nAChRs examined in a variety of cell expression systems. We have demonstrated the functional expression, as homomeric nAChRs, of the Dα5 and Dα7 subunits in Xenopus oocytes by their co-expression with the molecular chaperone RIC-3. Also, using a similar approach, we have demonstrated the functional expression of a heteromeric ‘triplet’ nAChR (Dα5 + Dα6 + Dα7) with substantially higher apparent affinity for acetylcholine than is seen with other subunit combinations. In addition, specific cell-surface binding of [125I]-α-bungarotoxin was detected in both Drosophila and mammalian cell lines when Dα5 was co-expressed with Dα6 and RIC-3. In contrast, co-expression of additional subunits (including Dα7) with Dα5 and Dα6 prevented specific binding of [125I]-α-bungarotoxin in cell lines, suggesting that co-assembly with other nAChR subunits can block maturation of correctly folded nAChRs in some cellular environments.

Conclusion
Data are presented demonstrating the ability of the Drosophila Dα5 and Dα7 subunits to generate functional homomeric and also heteromeric nAChRs.
High-throughput sequencing of black pepper root transcriptome
Authors: Gordo Sheila MC , Pinheiro Daniel G , Moreira Edith CO , Rodrigues Simone M , Poltronieri Marli C , de Lemos Oriel F , da Silva Israel Tojal , Ramos Rommel TJ , Silva Artur , Schneider Horacio , Silva Wilson A , Sampaio Iracilda , Darnet Sylvain 
Published: September 2012

Abstract

Background
Black pepper (Piper nigrum L.) is one of the most popular spices in the world. It is used in cooking and the preservation of food and even has medicinal properties. Losses in production from disease are a major limitation in the culture of this crop. The major diseases are root rot and foot rot, which are results of root infection by Fusarium solani and Phytophtora capsici, respectively. Understanding the molecular interaction between the pathogens and the host’s root region is important for obtaining resistant cultivars by biotechnological breeding. Genetic and molecular data for this species, though, are limited. In this paper, RNA-Seq technology has been employed, for the first time, to describe the root transcriptome of black pepper.

Results
The root transcriptome of black pepper was sequenced by the NGS SOLiD platform and assembled using the multiple-k method. Blast2Go and orthoMCL methods were used to annotate 10338 unigenes. The 4472 predicted proteins showed about 52% homology with the Arabidopsis proteome. Two root proteomes identified 615 proteins, which seem to define the plant’s root pattern. Simple-sequence repeats were identified that may be useful in studies of genetic diversity and may have applications in biotechnology and ecology.

Conclusions
This dataset of 10338 unigenes is crucially important for the biotechnological breeding of black pepper and the ecogenomics of the Magnoliids, a major group of basal angiosperms.
Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns
Authors: Kotowski Maciej , Safranow Krzysztof , Kawa Miłosz P , Lewandowska Joanna , Kłos Patrycja , Dziedziejko Violetta , Paczkowska Edyta , Czajka Ryszard , Celewicz Zbigniew , Rudnicki Jacek , Machaliński Bogusław 
Published: September 2012

Abstract

Background
The frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity.

Methods
The study groups consisted of 90 preterm (23–36 weeks of gestational age) and 52 full-term (37–41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (β-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables.

Results
We found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p < 0.0001) and extensively decreases in preterm babies during next six weeks after birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of premature neonates is higher than those obtained from CB of full-term infants and strongly correlates with the number of CB-derived CSPCs.

Conclusion
We conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.
Why physicians and nurses ask (or don’t) about partner violence: a qualitative analysis
Authors: Beynon Charlene E , Gutmanis Iris A , Tutty Leslie M , Wathen C Nadine , MacMillan Harriet L 
Published: September 2012

Abstract

Background
Intimate partner violence (IPV) against women is a serious public health issue and is associated with significant adverse health outcomes. The current study was undertaken to: 1) explore physicians’ and nurses’ experiences, both professional and personal, when asking about IPV; 2) determine the variations by discipline; and 3) identify implications for practice, workplace policy and curriculum development.

Methods
Physicians and nurses working in Ontario, Canada were randomly selected from recognized discipline-specific professional directories to complete a 43-item mailed survey about IPV, which included two open-ended questions about barriers and facilitators to asking about IPV. Text from the open-ended questions was transcribed and analyzed using inductive content analysis. In addition, frequencies were calculated for commonly described categories and the Fisher’s Exact Test was performed to determine statistical significance when examining nurse/physician differences.

Results
Of the 931 respondents who completed the survey, 769 (527 nurses, 238 physicians, four whose discipline was not stated) provided written responses to the open-ended questions. Overall, the top barriers to asking about IPV were lack of time, behaviours attributed to women living with abuse, lack of training, language/cultural practices and partner presence. The most frequently reported facilitators were training, community resources and professional tools/protocols/policies. The need for additional training was a concern described by both groups, yet more so by nurses. There were statistically significant differences between nurses and physicians regarding both barriers and facilitators, most likely related to differences in role expectations and work environments.

Conclusions
This research provides new insights into the complexities of IPV inquiry and the inter-relationships among barriers and facilitators faced by physicians and nurses. The experiences of these nurses and physicians suggest that more supports (e.g., supportive work environments, training, mentors, consultations, community resources, etc.) are needed by practitioners. These findings reflect the results of previous research yet offer perspectives on why barriers persist. Multifaceted and intersectoral approaches that address individual, interpersonal, workplace and systemic issues faced by nurses and physicians when inquiring about IPV are required. Comprehensive frameworks are needed to further explore the many issues associated with IPV inquiry and the interplay across these issues.
Suboptimal chemotherapy is an adverse prognostic factor in osteosarcoma
Authors: Yong Bicheng , Tan Pingxian , Yin Junqiang , Zou Changye , Xie Xianbiao , Wang Jin , Huang Gang , Wang Qianyong , Shen Jingnan 
Published: September 2012

AbstractBackgroundWe sought to determine whether suboptimal chemotherapy compromised the prognosis of osteosarcoma patients.MethodsA total of 132 eligible patients who underwent chemotherapy between 1998 and 2008 were identified in our database. Information regarding patient demographics, clinical characteristics, and survival status were extracted for analysis. Optimal chemotherapy was defined as receipt of ≥80% of the planned dose intensity of prescribed agents within the planned durations.ResultsThe use of optimal chemotherapy resulted in an overall survival benefit withP =0.006. Patients who failed to complete the optimal chemotherapy protocol had a dismal prognosis of 30.8% overall survival over five years, whereas those who completed the optimal chemotherapy had an overall survival rate over five years of 65.3%. Based on multivariate analysis, patients who were treated with a suboptimal protocol had a higher risk of relapse, metastasis and mortality. The hazard ratio (HR) of recurrence or death for the suboptimal chemotherapy group was as high as 2.512 over that of the optimal chemotherapy group (HR = 2.512, 95% confidence interval = 1.242 to 3.729).ConclusionsChemotherapy is a significant independent prognostic variable, and suboptimal chemotherapy was found to have a detrimental effect on the outcome of patients with osteosarcoma.
Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management
Authors: Schreinemakers Jennifer MJ , Vriens Menno R , Munoz-Perez Nuria , Guerrero Marlon A , Suh Insoo , Rinkes Inne HM Borel , Gosnell Jessica , Shen Wen T , Clark Orlo H , Duh Quan-Yang 
Published: September 2012

Abstract

Background
To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management.

Methods
From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared.

Results
Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease.

Conclusion
Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.