bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Decade of the Moderate Resolution Imaging Spectroradiometer: Is a Solar–Cloud Link Detectable?
Authors: Laken Benjamin , Pallé Enric , Miyahara Hiroko 
Published: January 2012

Abstract
Based on the results of decadal correlation studies between the International Satellite Cloud Climatology Project–detected cloud anomalies and the galactic cosmic ray (GCR) flux, it has been suggested that a relationship exists between solar activity and cloud cover. If valid, such a relationship could have important implications for scientists’ understanding of recent climate change. In this work, an analysis of the first decade of Moderate Resolution Imaging Spectroradiometer (MODIS)–detected cloud anomalies are presented, and the data at global and local geographical resolutions to total solar irradiance (TSI), GCR variations, and the multivariate El Niño–Southern Oscillation index are compared. The study identifies no statistically significant correlations between cloud anomalies and TSI/GCR variations, and concludes that solar-related variability is not a primary driver of monthly to annual MODIS cloud variability. The authors observe a net increase in cloud detected by MODIS over the past decade of ~0.58%, arising from a combination of a reduction in high- to midlevel cloud (−0.31%) and an increase in low-level cloud (0.89%); these long-term changes may be largely attributed to ENSO-induced cloud variability.
A Method for Estimating Planetary Boundary Layer Heights and Its Application over the ARM Southern Great Plains Site
Authors: Schmid Paul , Niyogi Dev 
Published: January 2012

Abstract
A new objective method to determine the height of the planetary boundary layer (PBL) is presented here. PBL heights are computed using the statistical variance and kurtosis of dewpoint and virtual potential temperature differences measured from radio soundings at the U.S. Department of Energy’s Atmospheric Radiation Measurement (ARM) program at the Southern Great Plains (SGP) site. These heights are compared with those derived from lidar, also on the site, and with gridded model data from the North American Regional Reanalysis (NARR). A climatology of mean heights in the early (1800 UTC) and late (0000 UTC) afternoon from 2002 to 2010 is presented to show the effectiveness of the method. Future work using the new method include producing an observational climatology of PBL heights and understanding the aerosol loading within the PBL as well as a better understanding of the coupling between the surface and free atmosphere.
Organizational change
Authors: Goodman Elisabeth , Loh Lucy 
Published: January 2012

Change is again in the spotlight. Much of the current debate about organizational change is focusing on large scale changes, e.g. public sector reshaping or the role of the third sector, for example, and many private sector organizations are working hard on internal efficiencies. All of these bring huge challenges. But what about the people and the teams within these organizations, who must continue to deliver today as well as achieve changes to their own roles and services for delivery tomorrow? This article describes some of the current drivers of change, and the challenges for teams. It highlights a number of models and approaches which describe the cycle of change and the elements of team effectiveness, and gives practical advice on how to use those to develop and support teams in a time of change. Our advice is grounded in good practice gained through real life experience, with practical tips and suggestions. These will help readers to build and rebuild teams so that they remain effective and the people in them motivated and aligned to the organization’s goals.
Platelet-Rich Plasma or Hyaluronate in the Management of Osteochondral Lesions of the Talus
Authors: Mei-Dan Omer , Carmont Michael R. , Laver Lior , Mann Gideon , Maffulli Nicola , Nyska Meir 
Published: January 2012

Background: Nonoperative options for osteochondral lesions (OCLs) of the talar dome are limited, and currently, there is a lack of scientific evidence to guide management. Purpose: To evaluate the short-term efficacy and safety of platelet-rich plasma (PRP) compared with hyaluronic acid (HA) in reducing pain and disability caused by OCLs of the ankle. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Thirty-two patients aged 18 to 60 years were allocated to a treatment by intra-articular injections of either HA (group 1) or PRP (plasma rich in growth factors [PRGF] technique, group 2) for OCLs of the talus. Thirty OCLs, 15 per arm, received 3 consecutive intra-articular therapeutic injections and were followed for 28 weeks. The efficacy of the injections in reducing pain and improving function was assessed at each visit using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS); a visual analog scale (VAS) for pain, stiffness, and function; and the subjective global function score. Results: The majority of patients were men (n = 23; 79%). The AHFS score improved from 66 and 68 to 78 and 92 in groups 1 and 2, respectively, from baseline to week 28 ( P < .0001), favoring PRP ( P < .05). Mean VAS scores (1 = asymptomatic, 10 = severe symptoms) decreased for pain (group 1: 5.6 to 3.1; group 2: 4.1 to 0.9), stiffness (group 1: 5.1 to 2.9; group 2: 5.0 to 0.8), and function (group 1: 5.8 to 3.5; group 2: 4.7 to 0.8) from baseline to week 28 ( P < .0001), favoring PRP ( P < .05 for stiffness, P < .01 for function, P > .05 for pain). Subjective global function scores, reported on a scale from 0 to 100 (with 100 representing healthy, preinjury function) improved from 56 and 58 at baseline to 73 and 91 by week 28 for groups 1 and 2, respectively ( P < .01 in favor of PRP). Conclusion: Osteochondral lesions of the ankle treated with intra-articular injections of PRP and HA resulted in a decrease in pain scores and an increase in function for at least 6 months, with minimal adverse events. Platelet-rich plasma treatment led to a significantly better outcome than HA.
Qualitative exploration of psychological factors associated with spinal cord stimulation outcome
Authors: Sparkes Elizabeth , Duarte Rui V , Raphael Jon H , Denny Elaine , Ashford Robert L 
Published: January 2012

Background and aim: Spinal cord stimulation (SCS) is a last resort treatment for chronic pain consisting of an implantable pulse generator connected to leads placed in the epidural space of the spinal cord. Effective in reducing chronic pain, however, efficacy has been found to decrease over time. Psychological factors affecting outcome of SCS have been investigated through quantitative methods, but these have failed to provide confident predictors. We aimed to investigate via a qualitative approach, the experience of SCS following 1 year of therapy. Methods: Thirteen chronic non-cancer pain participants were interviewed. All participants had been trialled with SCS. The majority had gone on to full implantation with varying degrees of pain relief. Thematic analysis was employed to analyse the data from the interviews. Results: Interviews resulted in findings that previous quantitative studies had failed to uncover. Two emergent core themes surfaced: ‘coping with pain’ and ‘SCS treatment’. The effect of emotion upon coping was recurrent. Participants divided the SCS experience into information provision, independence and unexpected experiences. Conclusion: The findings provide context for the patients’ experience of SCS. This research suggests that improved preparation prior to SCS including information provision, CBT and contact with expert patients may be of value.
Delineation of antigen-specific and antigen-nonspecific CD8+ memory T-cell responses after cytokine-based cancer immunotherapy
Authors: Tietze Julia K. , Wilkins Danice E. C. , Sckisel Gail D. , Bouchlaka Myriam N. , Alderson Kory L. , Weiss Jonathan M. , Ames Erik , Bruhn Kevin W. , Craft Noah , Wiltrout Robert H. , Longo Dan L. , Lanier Lewis L. , Blazar Bruce R. , Redelman Doug , Murphy William J. 
Published: January 2012

AbstractMemory T cells exhibit tremendous antigen specificity within the immune system and accumulate with age. Our studies reveal an antigen-independent expansion of memory, but not naive, CD8+ T cells after several immunotherapeutic regimens for cancer resulting in a distinctive phenotype. Signaling through T-cell receptors (TCRs) or CD3 in both mouse and human memory CD8+ T cells markedly up-regulated programmed death-1 (PD-1) and CD25 (IL-2 receptor α chain), and led to antigen-specific tumor cell killing. In contrast, exposure to cytokine alone in vitro or with immunotherapy in vivo did not up-regulate these markers but resulted in expanded memory CD8+ T cells expressing NKG2D, granzyme B, and possessing broadly lytic capabilities. Blockade of NKG2D in mice also resulted in significantly diminished antitumor effects after immunotherapy. Treatment of TCR-transgenic mice bearing nonantigen expressing tumors with immunotherapy still resulted in significant antitumor effects. Human melanoma tissue biopsies obtained from patients after topically applied immunodulatory treatment resulted in increased numbers of these CD8+ CD25− cells within the tumor site. These findings demonstrate that memory CD8+ T cells can express differential phenotypes indicative of adaptive or innate effectors based on the nature of the stimuli in a process conserved across species.
The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies
Authors: Dennis Jessica , Johnson Candice Y. , Adediran Adeniyi Samuel , de Andrade Mariza , Heit John A. , Morange Pierre-Emmanuel , Trégouët David-Alexandre , Gagnon France 
Published: January 2012

AbstractThe endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation of the protein C anticoagulant pathway, and therefore may play a role in the etiology of thrombotic disorders. The rs867186 single-nucleotide polymorphism in the PROCR gene (g.6936A > G, c.4600A > G), resulting in a serine-to-glycine substitution at codon 219, has been associated with reduced activation of the protein C pathway, although its association with thrombosis risk remains unclear. The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous thromboembolism (VTE) and myocardial infarction (MI), which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2011 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Twelve candidate genes and 13 genome-wide association studies were analyzed (11 VTE and 14 MI, including 37 415 cases and 84 406 noncases). Under the additive genetic model, the odds of VTE increased by a factor of 1.22 (95% confidence interval, 1.11-1.33, P < .001) for every additional copy of the G allele. No evidence for association with MI was observed.
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML
Authors: Li Zejuan , Huang Hao , Li Yuanyuan , Jiang Xi , Chen Ping , Arnovitz Stephen , Radmacher Michael D. , Maharry Kati , Elkahloun Abdel , Yang Xinan , He Chunjiang , He Miao , Zhang Zhiyu , Dohner Konstanze , Neilly Mary Beth , Price Colles , Lussier Yves A. , Zhang Yanming , Larson Richard A. , Le Beau Michelle M. , Caligiuri Michael A. , Bullinger Lars , Valk Peter J. M. , Delwel Ruud , Lowenberg Bob , Liu Paul P. , Marcucci Guido , Bloomfield Clara D. , Rowley Janet D. , Chen Jianjun 
Published: January 2012

Abstract
Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
A neuronal death model: overexpression of neuronal intermediate filament protein peripherin in PC12 cells
Authors: Lee Wen-Ching , Chen Yun-Yu , Kan Daphne , Chien Chung-Liang 
Published: January 2012

AbstractBackgroundAbnormal accumulation of neuronal intermediate filament (IF) is a pathological indicator of some neurodegenerative disorders. However, the underlying neuropathological mechanisms of neuronal IF accumulation remain unclear. A stable clone established from PC12 cells overexpressing a GFP-Peripherin fusion protein (pEGFP-Peripherin) was constructed for determining the pathway involved in neurodegeneration by biochemical, cell biology, and electronic microscopy approaches. In addition, pharmacological approaches to preventing neuronal death were also examined.ResultsResults of this study showed that TUNEL positive reaction could be detected in pEGFP-Peripherin cells. Swollen mitochondria and endoplasmic reticulum (ER) were seen by electron microscopy in pEGFP-Peripherin cells on day 8 of nerve growth factor (NGF) treatment. Peripherin overexpression not only led to the formation of neuronal IF aggregate but also causes aberrant neuronal IF phosphorylation and mislocation. Western blots showed that calpain, caspase-12, caspase-9, and caspase-3 activity was upregulated. Furthermore, treatment with calpain inhibitor significantly inhibited cell death.ConclusionsThese results suggested that the cytoplasmic neuronal IF aggregate caused by peripherin overexpression may induce aberrant neuronal IF phosphorylation and mislocation subsequently trapped and indirectly damaged mitochondria and ER. We suggested that the activation of calpain, caspase-12, caspase-9, and caspase-3 were correlated to the dysfunction of the ER and mitochondria in our pEGFP-Peripherin cell model. The present study suggested that pEGFP-Peripherin cell clones could be a neuronal death model for future studies in neuronal IFs aggregate associated neurodegeneration.
Core module biomarker identification with network exploration for breast cancer metastasis
Authors: Yang Ruoting , Daigle Bernie J , Petzold Linda R , Doyle Francis J 
Published: January 2012

Abstract

Background
In a complex disease, the expression of many genes can be significantly altered, leading to the appearance of a differentially expressed "disease module". Some of these genes directly correspond to the disease phenotype, (i.e. "driver" genes), while others represent closely-related first-degree neighbours in gene interaction space. The remaining genes consist of further removed "passenger" genes, which are often not directly related to the original cause of the disease. For prognostic and diagnostic purposes, it is crucial to be able to separate the group of "driver" genes and their first-degree neighbours, (i.e. "core module") from the general "disease module".

Results
We have developed COMBINER: COre Module Biomarker Identification with Network ExploRation. COMBINER is a novel pathway-based approach for selecting highly reproducible discriminative biomarkers. We applied COMBINER to three benchmark breast cancer datasets for identifying prognostic biomarkers. COMBINER-derived biomarkers exhibited 10-fold higher reproducibility than other methods, with up to 30-fold greater enrichment for known cancer-related genes, and 4-fold enrichment for known breast cancer susceptible genes. More than 50% and 40% of the resulting biomarkers were cancer and breast cancer specific, respectively. The identified modules were overlaid onto a map of intracellular pathways that comprehensively highlighted the hallmarks of cancer. Furthermore, we constructed a global regulatory network intertwining several functional clusters and uncovered 13 confident "driver" genes of breast cancer metastasis.

Conclusions
COMBINER can efficiently and robustly identify disease core module genes and construct their associated regulatory network. In the same way, it is potentially applicable in the characterization of any disease that can be probed with microarrays.
Fine scale analysis of gene expression in Drosophila melanogaster gonads reveals Programmed cell death 4 promotes the differentiation of female germline stem cells
Authors: Cash Amy C , Andrews Justen 
Published: January 2012

Abstract
Background
Germline stem cells (GSCs) are present in the gonads of Drosophila females and males, and their proper maintenance, as well as their correct differentiation, is essential for fertility and fecundity. The molecular characterization of factors involved in maintenance and differentiation is a major goal both in Drosophila and stem cell research. While genetic studies have identified many of these key factors, the use of genome-wide expression studies holds the potential to greatly increase our knowledge of these pathways.

Results
Here we report a genome-wide expression study that uses laser cutting microdissection to isolate germline stem cells, somatic niche cells, and early differentiating germ cells from female and male gonads. Analysis of this data, in association with two previously published genome-wide GSC data sets, revealed sets of candidate genes as putatively expressed in specific cell populations. Investigation of one of these genes, CG10990 the Drosophila ortholog of mammalian Programmed cell death 4 (Pdcd4), reveals expression in female and male germline stem cells and early differentiating daughter cells. Functional analysis demonstrates that while it is not essential for oogenesis or spermatogenesis, it does function to promote the differentiation of GSCs in females. Furthermore, in females, Pdcd4 genetically interacts with the key differentiation gene bag of marbles (bam) and the stem cell renewal factor eIF4A, suggesting a possible pathway for its function in differentiation.

Conclusions
We propose that Pdcd4 promotes the differentiation of GSC daughter cells by relieving the eIF4A-mediated inhibition of Bam.
Rates of evolution in stress-related genes are associated with habitat preference in two Cardamine lineages
Authors: Ometto Lino , Li Mingai , Bresadola Luisa , Varotto Claudio 
Published: January 2012

Abstract

Background
Elucidating the selective and neutral forces underlying molecular evolution is fundamental to understanding the genetic basis of adaptation. Plants have evolved a suite of adaptive responses to cope with variable environmental conditions, but relatively little is known about which genes are involved in such responses. Here we studied molecular evolution on a genome-wide scale in two species of Cardamine with distinct habitat preferences: C. resedifolia, found at high altitudes, and C. impatiens, found at low altitudes. Our analyses focussed on genes that are involved in stress responses to two factors that differentiate the high- and low-altitude habitats, namely temperature and irradiation.

Results
High-throughput sequencing was used to obtain gene sequences from C. resedifolia and C. impatiens. Using the available A. thaliana gene sequences and annotation, we identified nearly 3,000 triplets of putative orthologues, including genes involved in cold response, photosynthesis or in general stress responses. By comparing estimated rates of molecular substitution, codon usage, and gene expression in these species with those of Arabidopsis, we were able to evaluate the role of positive and relaxed selection in driving the evolution of Cardamine genes. Our analyses revealed a statistically significant higher rate of molecular substitution in C. resedifolia than in C. impatiens, compatible with more efficient positive selection in the former. Conversely, the genome-wide level of selective pressure is compatible with more relaxed selection in C. impatiens. Moreover, levels of selective pressure were heterogeneous between functional classes and between species, with cold responsive genes evolving particularly fast in C. resedifolia, but not in C. impatiens.

Conclusions
Overall, our comparative genomic analyses revealed that differences in effective population size might contribute to the differences in the rate of protein evolution and in the levels of selective pressure between the C. impatiens and C. resedifolia lineages. The within-species analyses also revealed evolutionary patterns associated with habitat preference of two Cardamine species. We conclude that the selective pressures associated with the habitats typical of C. resedifolia may have caused the rapid evolution of genes involved in cold response.
Analysis of genome-wide association study data using the protein knowledge base
Authors: Ballouz Sara , Liu Jason Y , Oti Martin , Gaeta Bruno , Fatkin Diane , Bahlo Melanie , Wouters Merridee A 
Published: January 2012

Abstract

Background
Genome-wide association studies (GWAS) aim to identify causal variants and genes for complex disease by independently testing a large number of SNP markers for disease association. Although genes have been implicated in these studies, few utilise the multiple-hit model of complex disease to identify causal candidates. A major benefit of multi-locus comparison is that it compensates for some shortcomings of current statistical analyses that test the frequency of each SNP in isolation for the phenotype population versus control.

Results
Here we developed and benchmarked several protocols for GWAS data analysis using different in-silico gene prediction and prioritisation methodologies. We adopted a high sensitivity approach to the data, using less conservative statistical SNP associations. Multiple gene search spaces, either of fixed-widths or proximity-based, were generated around each SNP marker. We used the candidate disease gene prediction system Gentrepid to identify candidates based on shared biomolecular pathways or domain-based protein homology. Predictions were made either with phenotype-specific known disease genes as input; or without a priori knowledge, by exhaustive comparison of genes in distinct loci. Because Gentrepid uses biomolecular data to find interactions and common features between genes in distinct loci of the search spaces, it takes advantage of the multi-locus aspect of the data.

Conclusions
Results suggest testing multiple SNP-to-gene search spaces compensates for differences in phenotypes, populations and SNP platforms. Surprisingly, domain-based homology information was more informative when benchmarked against gene candidates reported by GWA studies compared to previously determined disease genes, possibly suggesting a larger contribution of gene homologs to complex diseases than Mendelian diseases.