bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search for a Gene Expression Signature of Breast Cancer Local Recurrence in Young Women
Authors: Servant Nicolas , Bollet Marc A. , Halfwerk Hans , Bleakley Kevin , Kreike Bas , Jacob Laurent , Sie Daoud , Kerkhoven Ron M. , Hupé Philippe , Hadhri Rim , Fourquet Alain , Bartelink Harry , Barillot Emmanuel , Sigal-Zafrani Brigitte , van de Vijver Marc J. 
Published: January 2012

Abstract
Purpose: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.
Experimental Design: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.
Results: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.
Conclusions: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment. Clin Cancer Res; 18(6); 1704–15. ©2012 AACR.
Assessing Tracer Transport Algorithms and the Impact of Vertical Resolution in a Finite-Volume Dynamical Core
Authors: Kent James , Jablonowski Christiane , Whitehead Jared P. , Rood Richard B. 
Published: January 2012

Abstract
Modeling the transport of trace gases is an essential part of any atmospheric model. The tracer transport scheme in the Community Atmosphere Model finite-volume dynamical core (CAM-FV), which is part of the National Center for Atmospheric Research’s (NCAR’s) Community Earth System Model (CESM1), is investigated using multidimensional idealized advection tests. CAM-FV’s tracer transport algorithm makes use of one-dimensional monotonic limiters. The Colella–Sekora limiter, which is applied to increase accuracy where the data are smooth, is implemented into the CAM-FV framework, and compared with the more traditional monotonic limiter of the piecewise parabolic method (the default limiter). For 2D flow, CAM-FV splits dimensions, allowing overshoots and undershoots, with the Colella–Sekora limiter producing larger overshoots than the default limiter.
The impact of vertical resolution is also explored. A vertical Lagrangian coordinate is used in CAM-FV, and is periodically remapped back to a fixed Eulerian grid. For purely vertical motion, it is found that less-frequent remapping of the Lagrangian coordinate in CAM-FV improves results. For full 3D tests, the vertical component of the tracer transport dominates the error and limits the overall accuracy. If the vertical resolution is inadequate, increasing the horizontal resolution has almost no effect on accuracy. This is because the vertical resolution currently used in CAM version 5 may not be sufficiently fine enough to resolve some atmospheric tracers and provide accurate vertical advection. Idealized tests using tracers in a gravity wave agree with these results.
Thermal Injury Activates the eEF2K‐Dependent eEF2 Pathway in Pediatric Patients
Authors: Song Juquan , Finnerty Celeste C. , Herndon David N. , Kraft Robert , Boehning Darren , Brooks Natasha C. , Tompkins Ronald G. , Jeschke Marc G. 
Published: January 2012

Background:Burn induces a hypermetabolic state characterized by alterations in protein metabolism, which is associated with increased morbidity and mortality. Eukaryotic elongation factor 2 (eEF2) plays a crucial role in regulating protein synthesis in many diseases, but whether it participates in burn‐induced hypermetabolism is unclear. The aim of this study was to determine the expression of eEF2 and the upstream eEF2‐inactivating kinase, eEF2K, in severely burned pediatric patients.Methods:Eight pediatric patients (> 40% total body surface area) and 3 nonburned pediatric volunteers were enrolled. Muscle and skin biopsies were collected at early (0–10 days postburn [dpb]), middle (11–49 dpb), and late (50–365 dpb) time points. Resting energy expenditure (REE), body composition, and muscle protein fractional synthesis rate (FSR) were measured. Proteins were extracted and analyzed by Western blotting. To further investigate the protein synthesis pathway, microarray data from muscle and skin were examined from 22 nonburned and 20 burned children.Results:Burn patients exhibited a profound hypermetabolic response, as seen by a significant increase in REE (P < .05) and loss of lean body mass without altered muscle FSR, indicating a shift to catabolism after thermal injury. In muscle, the phosphorylation of eEF2K‐dependent eEF2 was down regulated early and middle postburn. Similar changes in eEF2K and eEF2 levels occurred in skin at the early time point. Total amounts of eEF2 and eEF2K were not altered.Conclusion:Burn induces prolonged activation of eEF2K and eEF2. Alterations in these mediators may contribute to profound hypermetabolism in severely burned patients.
Infrastructure, Economic Growth and Poverty Reduction in Africa
Authors: Jerome Afeikhena 
Published: January 2012

The relationship between infrastructure, growth and poverty is empirically robust in the macro- economic and microeconomic literature as well as in the rapidly evolving randomised field evaluation studies. This article appraises the role of infrastructure in economic growth and poverty alleviation in Africa. It notes that Africa’s infrastructure is still much below international standards in terms of quantity and quality. Access, affordability and quality of service continue to be key issues in all infrastructure sectors. Poverty was also not carefully addressed as part of the regulatory and other reform packages implemented during the 1990s. Not surprisingly, the infrastructure needs of the poor, the majority of who reside in rural and peri-urban areas have not been met and they continue to rely on unsafe, unreliable and often overpriced alternatives to compensate for the policy failures. Unlike the reforms of the 1990s which were shaped by ideological cleavages and blame game, there is gradually a coalescing of opinions on the reform agenda in the twenty-first century. The choice is no longer between a segregation of public and private provision but mutual collaboration between both actors. The public sector is now expected to play a much more important role in financing infrastructure than previously acknow-ledged, while the private sector should assist in meeting the significant needs associated with infrastructure construction, operation, and to some extent, financing in sectors such as telecommunications, energy generation, and transport services in which commercial and political risks are much lower. JEL Classification: F3, L3, L9, N17, 055
Self-reported panic attacks in adulthood: Relationship with injury, location and disclosure of childhood sexual abuse
Authors: Renner Lynette M , Coohey Carol , Ruch Gillian , O’Leary Patrick 
Published: January 2012

• Summary: Children’s long-term response to sexual abuse is likely to be influenced by its context, such as the location of the abuse, the severity of the abuse, their relationship to the abuser, and whether they disclose the abuse. In this study, we examine whether these factors increase the likelihood that children will experience panic attacks during adulthood. • Findings: This secondary analysis relied on a convenience sample of 92 participants who were recruited through community advertisements. In the multivariate model, adults who were injured during the sexual abuse, were sexually abused outside their home, who reported the sexual abuse was incest, and who were in midlife were more likely to experience panic attacks. Disclosing abuse and wanting to disclose abuse, but being unable to, were not related to panic attacks. • Applications: The results of this exploratory study need to be verified by other researchers using a larger sample. For children, discussing the location of the abuse could lead to a conversation about safe spaces and protective strategies.
Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer
Authors: Buchlis George , Podsakoff Gregory M. , Radu Antonetta , Hawk Sarah M. , Flake Alan W. , Mingozzi Federico , High Katherine A. 
Published: January 2012

AbstractIn previous work we transferred a human factor IX–encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.
IMWG consensus on maintenance therapy in multiple myeloma
Authors: Ludwig Heinz , Durie Brian G. M. , McCarthy Philip , Palumbo Antonio , San Miguel Jésus , Barlogie Bart , Morgan Gareth , Sonneveld Pieter , Spencer Andrew , Andersen Kenneth C. , Facon Thierry , Stewart Keith A. , Einsele Hermann , Mateos Maria-Victoria , Wijermans Pierre , Waage Anders , Beksac Meral , Richardson Paul G. , Hulin Cyrille , Niesvizky Ruben , Lokhorst Henk , Landgren Ola , Bergsagel P. Leif , Orlowski Robert , Hinke Axel , Cavo Michele , Attal Michel 
Published: January 2012

Abstract
Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.
Developing a powerful In Silico tool for the discovery of novel caspase-3 substrates: a preliminary screening of the human proteome
Authors: Ayyash Muneef , Tamimi Hashem , Ashhab Yaqoub 
Published: January 2012

Abstract

Background
Caspases are a family of cysteinyl proteases that regulate apoptosis and other biological processes. Caspase-3 is considered the central executioner member of this family with a wide range of substrates. Identification of caspase-3 cellular targets is crucial to gain further insights into the cellular mechanisms that have been implicated in various diseases including: cancer, neurodegenerative, and immunodeficiency diseases. To date, over 200 caspase-3 substrates have been identified experimentally. However, many are still awaiting discovery.

Results
Here, we describe a powerful bioinformatics tool that can predict the presence of caspase-3 cleavage sites in a given protein sequence using a Position-Specific Scoring Matrix (PSSM) approach. The present tool, which we call CAT3, was built using 227 confirmed caspase-3 substrates that were carefully extracted from the literature. Assessing prediction accuracy using 10 fold cross validation, our method shows AUC (area under the ROC curve) of 0.94, sensitivity of 88.83%, and specificity of 89.50%. The ability of CAT3 in predicting the precise cleavage site was demonstrated in comparison to existing state-of-the-art tools. In contrast to other tools which were trained on cleavage sites of various caspases as well as other similar proteases, CAT3 showed a significant decrease in the false positive rate. This cost effective and powerful feature makes CAT3 an ideal tool for high-throughput screening to identify novel caspase-3 substrates.
The developed tool, CAT3, was used to screen 13,066 human proteins with assigned gene ontology terms. The analyses revealed the presence of many potential caspase-3 substrates that are not yet described. The majority of these proteins are involved in signal transduction, regulation of cell adhesion, cytoskeleton organization, integrity of the nucleus, and development of nerve cells.

Conclusions
CAT3 is a powerful tool that is a clear improvement over existing similar tools, especially in reducing the false positive rate. Human proteome screening, using CAT3, indicate the presence of a large number of possible caspase-3 substrates that exceed the anticipated figure. In addition to their involvement in various expected functions such as cytoskeleton organization, nuclear integrity and adhesion, a large number of the predicted substrates are remarkably associated with the development of nerve tissues.
Characterization of the C. elegans erlin homologue
Authors: Hoegg Maja B , Robbins Stephen M , McGhee James D 
Published: January 2012

Abstract

Background
Erlins are highly conserved proteins associated with lipid rafts within the endoplasmic reticulum (ER). Biochemical studies in mammalian cell lines have shown that erlins are required for ER associated protein degradation (ERAD) of activated inositol-1,4,5-trisphosphate receptors (IP3Rs), implying that erlin proteins might negatively regulate IP3R signalling. In humans, loss of erlin function appears to cause progressive intellectual disability, motor dysfunction and joint contractures. However, it is unknown if defects in IP3R ERAD are the underlying cause of this disease phenotype, whether ERAD of activated IP3Rs is the only function of erlin proteins, and what role ERAD plays in regulating IP3R-dependent processes in the context of an intact animal or embryo. In this study, we characterize the erlin homologue of the nematode Caenorhabditis elegans and examine erlin function in vivo. We specifically set out to test whether C. elegans erlin modulates IP3R-dependent processes, such as egg laying, embryonic development and defecation rates. We also explore the possibility that erlin might play a more general role in the ERAD pathway of C. elegans.

Results
We first show that the C. elegans erlin homologue, ERL-1, is highly similar to mammalian erlins with respect to amino acid sequence, domain structure, biochemical properties and subcellular location. ERL-1 is present throughout the C. elegans embryo; in adult worms, ERL-1 appears restricted to the germline. The expression pattern of ERL-1 thus only partially overlaps with that of ITR-1, eliminating the possibility of ERL-1 being a ubiquitous and necessary regulator of ITR-1. We show that loss of ERL-1 does not affect overall phenotype, or alter brood size, embryonic development or defecation cycle length in either wild type or sensitized itr-1 mutant animals. Moreover we show that ERL-1 deficient worms respond normally to ER stress conditions, suggesting that ERL-1 is not an essential component of the general ERAD pathway.

Conclusions
Although loss of erlin function apparently causes a strong phenotype in humans, no such effect is seen in C. elegans. C. elegans erlin does not appear to be a ubiquitous major modulator of IP3 receptor activity nor does erlin appear to play a major role in ERAD.
An R package "VariABEL" for genome-wide searching of potentially interacting loci by testing genotypic variance heterogeneity
Authors: Struchalin Maksim V , Amin Najaf , Eilers Paul HC , van Duijn Cornelia M , Aulchenko Yurii S 
Published: January 2012

Abstract

Background
Hundreds of new loci have been discovered by genome-wide association studies of human traits. These studies mostly focused on associations between single locus and a trait. Interactions between genes and between genes and environmental factors are of interest as they can improve our understanding of the genetic background underlying complex traits. Genome-wide testing of complex genetic models is a computationally demanding task. Moreover, testing of such models leads to multiple comparison problems that reduce the probability of new findings. Assuming that the genetic model underlying a complex trait can include hundreds of genes and environmental factors, testing of these models in genome-wide association studies represent substantial difficulties.
We and Pare with colleagues (2010) developed a method allowing to overcome such difficulties. The method is based on the fact that loci which are involved in interactions can show genotypic variance heterogeneity of a trait. Genome-wide testing of such heterogeneity can be a fast scanning approach which can point to the interacting genetic variants.

Results
In this work we present a new method, SVLM, allowing for variance heterogeneity analysis of imputed genetic variation. Type I error and power of this test are investigated and contracted with these of the Levene's test. We also present an R package, VariABEL, implementing existing and newly developed tests.

Conclusions
Variance heterogeneity analysis is a promising method for detection of potentially interacting loci. New method and software package developed in this work will facilitate such analysis in genome-wide context.
Expression profiling reveals Spot 42 small RNA as a key regulator in the central metabolism of Aliivibrio salmonicida
Authors: Hansen Geir Å , Ahmad Rafi , Hjerde Erik , Fenton Christopher G , Willassen Nils-Peder , Haugen Peik 
Published: January 2012

Abstract

Background
Spot 42 was discovered in Escherichia coli nearly 40 years ago as an abundant, small and unstable RNA. Its biological role has remained obscure until recently, and is today implicated in having broader roles in the central and secondary metabolism. Spot 42 is encoded by the spf gene. The gene is ubiquitous in the Vibrionaceae family of gamma-proteobacteria. One member of this family, Aliivibrio salmonicida, causes cold-water vibriosis in farmed Atlantic salmon. Its genome encodes Spot 42 with 84% identity to E. coli Spot 42.

Results
We generated a A. salmonicida spf deletion mutant. We then used microarray and Northern blot analyses to monitor global effects on the transcriptome in order to provide insights into the biological roles of Spot 42 in this bacterium. In the presence of glucose, we found a surprisingly large number of ≥ 2X differentially expressed genes, and several major cellular processes were affected. A gene encoding a pirin-like protein showed an on/off expression pattern in the presence/absence of Spot 42, which suggests that Spot 42 plays a key regulatory role in the central metabolism by regulating the switch between fermentation and respiration. Interestingly, we discovered an sRNA named VSsrna24, which is encoded immediately downstream of spf. This new sRNA has an expression pattern opposite to that of Spot 42, and its expression is repressed by glucose.

Conclusions
We hypothesize that Spot 42 plays a key role in the central metabolism, in part by regulating the pyruvat dehydrogenase enzyme complex via pirin.
Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells
Authors: Lim Do Young , Cho Han Jin , Kim Jongdai , Nho Chu Won , Lee Ki Won , Park Jung Han Yoon 
Published: January 2012

Abstract

Background
Luteolin is a 3',4',5,7-tetrahydroxyflavone found in various fruits and vegetables. We have shown previously that luteolin reduces HT-29 cell growth by inducing apoptosis and cell cycle arrest. The objective of this study was to examine whether luteolin downregulates the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in HT-29 cells.

Methods
In order to assess the effects of luteolin and/or IGF-I on the IGF-IR signaling pathway, cells were cultured with or without 60 μmol/L luteolin and/or 10 nmol/L IGF-I. Cell proliferation, DNA synthesis, and IGF-IR mRNA levels were evaluated by a cell viability assay, [3H]thymidine incorporation assays, and real-time polymerase chain reaction, respectively. Western blot analyses, immunoprecipitation, and in vitro kinase assays were conducted to evaluate the secretion of IGF-II, the protein expression and activation of IGF-IR, and the association of the p85 subunit of phophatidylinositol-3 kinase (PI3K) with IGF-IR, the phosphorylation of Akt and extracellular signal-regulated kinase (ERK)1/2, and cell division cycle 25c (CDC25c), and PI3K activity.

Results
Luteolin (0 - 60 μmol/L) dose-dependently reduced the IGF-II secretion of HT-29 cells. IGF-I stimulated HT-29 cell growth but did not abrogate luteolin-induced growth inhibition. Luteolin reduced the levels of the IGF-IR precursor protein and IGF-IR transcripts. Luteolin reduced the IGF-I-induced tyrosine phosphorylation of IGF-IR and the association of p85 with IGF-IR. Additionally, luteolin inhibited the activity of PI3K activity as well as the phosphorylation of Akt, ERK1/2, and CDC25c in the presence and absence of IGF-I stimulation.

Conclusions
The present results demonstrate that luteolin downregulates the activation of the PI3K/Akt and ERK1/2 pathways via a reduction in IGF-IR signaling in HT-29 cells; this may be one of the mechanisms responsible for the observed luteolin-induced apoptosis and cell cycle arrest.