bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caveolin 1 Is Overexpressed and Amplified in a Subset of Basal-like and Metaplastic Breast Carcinomas: A Morphologic, Ultrastructural, Immunohistochemical, and In situ Hybridization Analysis
Authors: Savage Kay , Lambros Maryou B.K. , Robertson David , Jones Robin L. , Jones Chris , Mackay Alan , James Michelle , Hornick Jason L. , Pereira Emilio M. , Milanezi Fernanda , Fletcher Christopher D.M. , Schmitt Fernando C. , Ashworth Alan , Reis-Filho Jorge S. 
Published: January 2007

Abstract
Purpose: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas.
Experimental Design: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization.
Results: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with ‘basal-like’ immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression.
Conclusions: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.
Pathologic and Molecular Heterogeneity in Imatinib-Stable or Imatinib-Responsive Gastrointestinal Stromal Tumors
Authors: Agaram Narasimhan P. , Besmer Peter , Wong Grace C. , Guo Tianhua , Socci Nicholas D. , Maki Robert G. , DeSantis Diann , Brennan Murray F. , Singer Samuel , DeMatteo Ronald P. , Antonescu Cristina R. 
Published: January 2007

Abstract
Purpose: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. Nearly all tumors express KIT protein, and most have an activating mutation in either KIT or PDGFRA. Therapy with selective tyrosine kinase inhibitors achieves a partial response or stable disease in ∼80% of patients with advanced GIST. However, after an initial clinical response, some patients develop imatinib resistance. Our goal was to investigate the spectrum of pathologic response and molecular alterations in a group of GIST patients, clinically defined as having imatinib-stable/imatinib-responsive lesions, who underwent surgical resection.
Experimental Design: Forty-three tumor nodules from 28 patients were available for pathologic and molecular analysis, which included genotyping for primary and secondary KIT/PDGFRA-mutations, cell cycle alterations, and biochemical activation status of KIT and downstream targets. The transcriptional changes of a subset of these tumors were compared with a group of imatinib-naive GISTs on a U133A Affymetrix expression platform.
Results: The histologic response did not correlate with imatinib therapy duration or with proliferative activity. Second-site KIT mutation was identified in only one tumor nodule. Activation of KIT and downstream targets was consistent in all tumors analyzed. Ultrastructurally, a subset of tumors showed a smooth muscle phenotype, which correlated with overexpression of genes involved in muscle differentiation and function.
Conclusions: The histologic response to imatinib is heterogeneous and does not correlate well with clinical response. Second-site KIT mutations are rare in imatinib-responsive GISTs compared with imatinib-resistant tumors. The gene signature of imatinib-response in GISTs showed alterations of cell cycle control as well as up-regulation of genes involved in muscle differentiation and function.
Constructing a Developmental Nation: The Challenges of Science, Technology, and Innovation in the Socioeconomic Transformation of Africa
Authors: Forje John 
Published: December 2006

AbstractThe major challenge facing Africa's socioeconomic transformation pivots on the gross absence of added value to its abundant natural resources. The continent is suffering from low human resources development, poor innovative capacity, and low productivity. This paper argues that, until the continent is able to develop its innovative, competitive, productive, and competence capacity, it will remain an underdeveloped polity exploited by the countries that master the driving forces of science, technology, research, innovation, and globalization in the development process.
Aid and Economic Growth in Pacific Island Countries: An Empirical Study of Aid Effectiveness in Fiji
Authors: Jayaraman  , Choong Chee-Keong 
Published: December 2006

AbstractPacific island countries (PICs), ever since their independence during the second half of the last century, have been among the world's top ten recipients of official development assistance (ODA) on a per capita basis. Until the mid 1990s, most of them were receiving aid from their erstwhile colonial masters for budgetary support. With the introduction of reforms in ODA delivery in the late 1990s with focus on program and project-tied aid, it was expected that aid would directly facilitate creation of much-needed growth enhancing infrastructures, physical as well as social, since domestic savings were found to be insufficient to finance them. However, continued stagnation in some PICs and deterioration in some others have been causing concerns. This paper seeks to examine the effectiveness of aid by undertaking a case study of Fiji, which has a longer time series data needed for econometric investigation. Based on the study's findings, the paper lists some policy conclusions relevant to the region.
International Training and the Digital Divide: Computer and Email Use in the Philippines
Authors: Ynalvez Marcus , Shrum Wesley 
Published: December 2006

AbstractWe describe digital technology utilization among knowledge producers who have experienced the alternative training structures. Using data from a face-to-face survey of Filipino scientists, we measure email utilization by scientists in terms of five aspects of access and use, and examine how they vary across place of graduate education. Our questions are: (1) How can we characterize peripheral scientists in terms of their contextual, personal, professional, and educational attributes? (2) How can we characterize their utilization of digital technology? (3) Are there indications that core-based graduate training translates into yet another significant dimension in digital inequality? Our finding suggests that the Philippine scientific system largely reflects the perspective of core-trained male scientists. Filipino scientists are able to utilize digital technology—personal computers, email, and the World Wide Web—but with important qualifications. While scientists at the core have the luxury of architectural, digital, and personal privacy in hardware-software-user interaction, such is not the case for Filipino scientists, who in general have to share digital resources in public spaces within formal organizations. Finally, place of graduation emerges as a new form shaping digital utilization and inequality. The diffusion of digital technology into peripheral scientific systems has been uneven along this newly emerging dimension. Digital inequality construed as simple hardware-software access and use is diminishing, but inequality at the level of advanced hardware-software interaction skills is fast emerging as a new dimension that encapsulates postcolonial relations in science.
On the Use of Quasi-crystal and Fractal Concepts in the Design of Affordable Rural/Urban Landscapes
Authors: Niang  , Soboyejo  
Published: December 2006

AbstractThis paper describes the use of quasi-crystal and fractal concepts in the design of rural and urban landscapes for affordable housing. These are shown to provide a framework for the efficient design of communities in which affordable homes are organized. In contrast to classical urban planning with single centers, distributed centers are integrated into the rural and urban landscapes using crystallographic and fractal concepts. These provide a framework for the dispersion of human traffic into well-identified regions. The combination of quasi-crystal and fractal theory is also used to provide a framework for the organic growth of communities around new distributed centers. These basic ideas are discussed within the context of a holistic framework for affordable housing.
On the Nature of Zonal Jet EOFs
Authors: Monahan Adam H. , Fyfe John C. 
Published: December 2006

Abstract
Analytic results are obtained for the mean and covariance structure of an idealized zonal jet that fluctuates in strength, position, and width. Through a systematic perturbation analysis, the leading empirical orthogonal functions (EOFs) and principal component (PC) time series are obtained. These EOFs are built of linear combinations of basic patterns corresponding to monopole, dipole, and tripole structures. The analytic results demonstrate that in general the individual EOF modes cannot be interpreted in terms of individual physical processes. In particular, while the dipole EOF (similar to the leading EOF of the midlatitude zonal mean zonal wind) describes fluctuations in jet position to leading order, its time series also contains contributions from fluctuations in strength and width. No simple interpretations of the other EOFs in terms of strength, position, or width fluctuations are possible. Implications of these results for the use of EOF analysis to diagnose physical processes of variability are discussed.
Comparison of Five Satellite-Derived Latent Heat Flux Products to Moored Buoy Data
Authors: Bourras Denis 
Published: December 2006

Abstract
Five satellite products of latent heat flux at the sea surface were compared to bulk fluxes calculated with data from 75 moored buoys, on almost 36 successive months from 1998 to 2000. The five products compared are the Hamburg Ocean Atmosphere Parameters and Fluxes from Satellite Dataset (HOAPS-2), the Japanese Ocean Flux Datasets with Use of Remote Sensing Observations (J-OFURO), the Jones dataset, the Goddard Satellite-Based Surface Turbulent Fluxes, version 2 (GSSTF-2), and the Bourras–Eymard–Liu dataset (BEL). The comparisons were performed under tropical and midlatitude environmental conditions, with three datasets based on 66 Tropical Atmosphere–Ocean array (TAO) buoys in the tropical Pacific, nine National Data Buoy Center (NDBC) buoys off the U.S. coasts, and four Met Office/Météo-France (UK–MF) moorings west of the United Kingdom and France, respectively. The satellite products did not all compare well to surface data. However, for each in situ dataset (TAO, NDBC, or UK–MF) at least one satellite product was found that had a good fit to surface data, that is, an rms deviation of 15–30 W m−2. It was found that HOAPS-2, J-OFURO, GSSTF-2, and BEL satellite products had moderate systematic errors with respect to surface data, from −13 to 26 W m−2, and small biases at midlatitudes (6–8 W m−2). Most of the satellite products were able to render the seasonal cycle of the latent heat flux calculated with surface data. The estimation of near-surface specific humidity was found to be problematic in most products, but it was best estimated in the HOAPS-2 product. GSSTF-2 and J-OFURO strongly overestimated the surface flux variations in time and space compared to surface data and to a flux climatology. With respect to TAO data, Jones fluxes yielded good results in terms of rms deviation (27 W m−2) but also presented a large systematic deviation. Overall, for application of the satellite fluxes to the world oceans, it was found that HOAPS-2 was the most appropriate product, whereas for application to the Tropics, BEL fluxes had the best performance in rms with respect to TAO data (24 W m−2).
Interactive Feedback between ENSO and the Indian Ocean in an Interactive Ensemble Coupled Model
Authors: Kug Jong-Seong , Kirtman Ben P. , Kang In-Sik 
Published: December 2006

Abstract
An interactive feedback between ENSO and the Indian Ocean is investigated using a Center for Ocean–Land–Atmosphere Studies (COLA) interactive ensemble coupled model. From a long-term simulation of the coupled GCM, it is shown that El Niño events terminate relatively rapidly when the Indian Ocean SST is anomalously warm. The anomalous Indian Ocean warming induces the anomalous easterlies over the western Pacific by modulating the Walker circulation. In turn, the anomalous easterlies generate oceanic-upwelling Kelvin waves over the western Pacific, which propagate eastward and accelerate the decay of the warm SST in the eastern Pacific. As a result, El Niño terminates relatively quickly, and the phase transition from El Niño to La Niña progresses rapidly. These interactive processes are consistent with those derived from the previous observational analyses.
Cystic fibrosis mortality and survival in the UK: 1947–2003
Authors: Dodge J. A. , Lewis P. A. , Stanton M. , Wilsher J. 
Published: December 2006

Data up to 1995 on the survival of 3-yr cohorts of patients with cystic fibrosis (CF) born in the UK in the period 1968–1992 have previously been published. The present study reports survival data up to the end of 2003 together with a 2003 population estimate.All subjects with CF born in the UK in the period 1968–1992 were identified up to 1997 by active enquiry through recognised CF clinics and other hospital consultants. Information from the death certification authorities up to the end of 2003 was added. Death certificates that could not be matched with UK Cystic Fibrosis Survey records were investigated and the data reconciled.The observed survival up to 2003 of CF patients born in 1978 was 55% for males and 49% for females. For 1988 and 1992 the data were 91 and 88%, and 97 and 96%, respectively. The estimated 2003 mid-year CF population was 8,284.The continuing improvement in survival of cystic fibrosis patients in successive cohorts means that the previous prediction of median survival of >50 yrs of age for individuals born in 2000 continues to look realistic, even in the absence of proven effective therapy aimed at correcting the basic cystic fibrosis defect.
High resolution melting analysis for the rapid and sensitive detection of mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell lung cancer
Authors: Krypuy Michael , Newnham Genni M , Thomas David M , Conron Matthew , Dobrovic Alexander 
Published: December 2006

Abstract

Background
The development of targeted therapies has created a pressing clinical need for the rapid and robust molecular characterisation of cancers. We describe here the application of high-resolution melting analysis (HRM) to screen for KRAS mutations in clinical cancer samples. In non-small cell lung cancer, KRAS mutations have been shown to identify a group of patients that do not respond to EGFR targeted therapies and the identification of these mutations is thus clinically important.

Methods
We developed a high-resolution melting (HRM) assay to detect somatic mutations in exon 2, notably codons 12 and 13 of the KRAS gene using the intercalating dye SYTO 9. We tested 3 different cell lines with known KRAS mutations and then examined the sensitivity of mutation detection with the cell lines using 189 bp and 92 bp amplicons spanning codons 12 and 13. We then screened for KRAS mutations in 30 non-small cell lung cancer biopsies that had been previously sequenced for mutations in EGFR exons 18–21.

Results
Known KRAS mutations in cell lines (A549, HCT116 and RPMI8226) were readily detectable using HRM. The shorter 92 bp amplicon was more sensitive in detecting mutations than the 189 bp amplicon and was able to reliably detect as little as 5–6% of each cell line DNA diluted in normal DNA. Nine of the 30 non-small cell lung cancer biopsies had KRAS mutations detected by HRM analysis. The results were confirmed by standard sequencing. Mutations in KRAS and EGFR were mutually exclusive.

Conclusion
HRM is a sensitive in-tube methodology to screen for mutations in clinical samples. HRM will enable high-throughput screening of gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer.
Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques
Authors: Metzner Karin J , Binley James M , Gettie Agegnehu , Marx Preston , Nixon Douglas F , Connor Ruth I 
Published: December 2006

Abstract

Background
Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV). Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT) inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir.

Results
Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055.

Conclusion
These results support the concept that anti-viral immunity acts synergistically with ART to augment drug efficacy by suppressing replication of viral variants with reduced drug sensitivity. Treatment strategies that seek to combine immunotherapeutic intervention as an adjunct to antiretroviral drugs may therefore confer added benefit by controlling replication of HIV-1, and reducing the likelihood of treatment failure due to the emergence of drug-resistant virus, thereby preserving treatment options.
Choroid plexus epithelial monolayers – a cell culture model from porcine brain
Authors: Baehr Carsten , Reichel Valeska , Fricker Gert 
Published: December 2006

AbstractBackgroundThe goal of the present study was to develop anin vitrochoroid plexus (CP) epithelial cell culture model for studying transport of protein-mediated drug secretion from blood to cerebrospinal fluid (CSF) andvice versa.MethodsCells were isolated by mechanical and enzymatic treatment of freshly isolated porcine plexus tissue. Epithelial cell monolayers were grown and CSF secretion and transepithelial resistance were determined. The expression of f-actin as well as the choroid plexus marker protein transthyretin (TTR), were assessed. The expression of the export proteins p-glycoprotein (Pgp, Abcb1) and multidrug resistance protein 1 (Mrp1, Abcc1) was studied by RT-PCR, Western-blot and immunofluorescence techniques and their functional activity was assessed by transport and uptake experiments.ResultsChoroid plexus epithelial cells were isolated in high purity and grown to form confluent monolayers. Filter-grown monolayers displayed transendothelial resistance (TEER) values in the range of 100 to 150 Ωcm2. Morphologically, the cells showed the typical net work of f-actin and expressed TTR at a high rate. The cultured cells were able to secrete CSF at a rate of 48.2 ± 4.6 μl/cm2/h over 2–3 hours. The ABC-export protein Mrp1 was expressed in the basolateral (blood-facing) membranes of cell monolayers and intact tissue. P-glycoprotein showed only low expression within the apical (CSF directed) membrane but was located more in sub-apical cell compartments. This finding was paralleled by the lack of directed excretion of p-glycoprotein substrates, verapamil and rhodamine 123.ConclusionIt was demonstrated that CP epithelium can be isolated and cultured, with cells growing into intact monolayers, fully differentiating and with properties resembling the tissuein vivo. Thus, the established primary porcine CP model, allowing investigation of complex transport processes, can be used as a reliable tool for analysis of xenobiotic transport across the blood-cerebrospinal fluid barrier (BCSFB).