bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the expression of the invasion-suppressor CRMP-1 by cyclooxygenase-2 inhibition via reciprocal regulation of Sp1 and C/EBPα
Authors: Wu Cheng-Chung , Lin Jau-Chen , Yang Shuenn-Chen , Lin Chiu-Wen , Chen Jeremy J.W. , Shih Jin-Yuan , Hong Tse-Ming , Yang Pan-Chyr 
Published: June 2008

Abstract
Collapsin response mediator protein-1 (CRMP-1) controls neural development and axonal growth but also acts as a cancer invasion suppressor. In this study, we investigated the transcriptional regulation of CRMP-1 expression. Using a serial deletion strategy, we identified a basal promoter region between nucleotides -100 and -180 in the 5′ flanking region of CRMP-1 (nucleotides -1,920 to +50) that contains multiple putative Sp1 and C/EBPα sites. Site-directed mutagenesis and deletion analysis revealed that the two C/EBPα sites, from nucleotides -122 to -133 and from nucleotides -101 to -113, are the most important regulatory elements. Gel-shift and antibody supershift assays showed that Sp1 protein was also present at this C/EBPα site, which overlaps with a Sp1 site. Overexpression of Sp1 decreased CRMP-1 promoter activity and protein expression, whereas overexpression of C/EBPα produced the opposite effect. Chromatin immunoprecipitation assays confirmed that Sp1 and C/EBPα compete for binding at the overlapping C/EBPα and Sp1 sites and reciprocally regulate CRMP-1 expression. Overexpression of cyclooxygenase-2 (COX-2) decreased CRMP-1 mRNA and protein expression. Conversely, the COX-2 inhibitor, celecoxib, induced a dose-dependent increase in CRMP-1 expression. COX-2 inhibition also decreased Sp1-DNA complex formation and inhibited cell invasion. We conclude that transcription of the invasion suppressor, CRMP-1, is reciprocally regulated at the promoter region by C/EBPα and Sp1. COX-2 inhibitors increase CRMP-1 expression by inhibiting Sp1-DNA complex formation and enhancing DNA binding of C/EBPα at the promoter. [Mol Cancer Ther 2008;7(6):1365–75]
Indices for Testing Neural Codes
Authors: Victor Jonathan D. , Nirenberg Sheila 
Published: June 2008

One of the most critical challenges in systems neuroscience is determining the neural code. A principled framework for addressing this can be found in information theory. With this approach, one can determine whether a proposed code can account for the stimulus-response relationship. Specifically, one can compare the transmitted information between the stimulus and the hypothesized neural code with the transmitted information between the stimulus and the behavioral response. If the former is smaller than the latter (i.e., if the code cannot account for the behavior), the code can be ruled out. The information-theoretic index most widely used in this context is Shannon's mutual information. The Shannon test, however, is not ideal for this purpose: while the codes it will rule out are truly nonviable, there will be some nonviable codes that it will fail to rule out. Here we describe a wide range of alternative indices that can be used for ruling codes out. The range includes a continuum from Shannon information to measures of the performance of a Bayesian decoder. We analyze the relationship of these indices to each other and their complementary strengths and weaknesses for addressing this problem.
Improved Daytime Column-Integrated Precipitable Water Vapor from Vaisala Radiosonde Humidity Sensors
Authors: Cady-Pereira K. E. , Shephard M. W. , Turner D. D. , Mlawer E. J. , Clough S. A. , Wagner T. J. 
Published: June 2008

Abstract
Accurate water vapor profiles from radiosondes are essential for long-term climate prediction, weather prediction, validation of remote sensing retrievals, and other applications. The Vaisala RS80, RS90, and RS92 radiosondes are among the more commonly deployed radiosondes in the world. However, numerous investigators have shown that the daytime water vapor profiles measured by these instruments present a significant dry bias due to the solar heating of the humidity sensor. This bias in the column-integrated precipitable water vapor (PWV), along with variability due to calibration, can be removed by scaling the humidity profile to agree with the PWV retrieved from a microwave radiometer (MWR), as has been demonstrated by several previous studies. Infrared radiative closure analyses have shown that the MWR PWV does not present daytime versus nighttime differences; thus, scaling by the MWR is a possible approach for removing the daytime dry bias. However, MWR measurements are not routinely available at all radiosonde launch sites. Starting from a long-term series of sonde and MWR PWV measurements from the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site, the authors have developed a simple correction to the column-integrated sonde PWV, derived from an analysis of the ratio of the MWR and sonde measurements; this correction is a function of the atmospheric transmittance as determined by the solar zenith angle, and it effectively removes the daytime dry bias at all solar zenith angles. The correction was validated by successfully applying it to an independent dataset from the ARM tropical western Pacific (TWP) site.
Representation Error of Oceanic Observations for Data Assimilation
Authors: Oke Peter R. , Sakov Pavel 
Published: June 2008

Abstract
A simple approach to the estimation of representation error (RE) of sea level (η), temperature (T), and salinity (S) observations for ocean data assimilation is described. It is assumed that the main source of RE is due to unresolved processes and scales in the model. Therefore, RE is calculated as a function of model resolution. The methods described here exploit the availability of mapped sea level anomalies (mSLAs) and along-track sea level anomalies (atSLAs). The mSLA fields or atSLA observations are regarded as the true ocean state. Here, they are averaged according to the resolution of the model grid, and the averaged field is taken as a representation of the true state on the given grid. The difference between the original data and the averaged field is then regarded as the RE for η. Subsequently, the RE is projected for η over depth using a standard technique, giving an estimate of the RE for T and S. Examples of RE estimates for an intermediate- and high-resolution global grid are presented. It is found that there is significant spatial variability in the RE for η, T, and S, with values that are typically greater than or comparable to measurement error, particularly in regions of strong mesoscale variability.
The use and effectiveness of granulocyte colony-stimulating factor in primary prophylaxis for febrile neutropenia in the outpatient setting
Authors: Tuffaha Haitham W , Treish Imad M , Zaru Luna 
Published: June 2008

Objectives. To conduct a drug utilization review (DUR) on the use of granulocyte colony-stimulating factor (G-CSF) and to study the effectiveness of this agent in preventing the incidence of febrile neutropenia (FN). Methods. Outpatients to whom G-CSF was dispensed were identified and their actual medical records were reviewed to verify patients who received G-CSF for primary prophylaxis. Literature was reviewed to determine the expected incidence and risk of FN for chemotherapy regimens used, and the compliance of prescribers with the institutional guidelines was evaluated. After that, the proportion of patients who developed FN was identified and compared to the expected incidence from literature. Data analysis was performed on the outcome of patient-cycle. Results. Of the 99 patient-cycles, 53 (53%) were compliant with guidelines whereas 46 (47%) were not. FN developed in 12 (12.1%, 95% CI = 5.7, 18.5) while the expected average incidence of FN was 32.7%. Eleven (21%, 95% CI = 10.1, 32.2) of the 53 patient-cycles that were compliant with guidelines developed FN, whereas one patient among the non-compliant group developed FN (2%, 95% CI = 0.0, 6.2). The expected incidence of FN was 42.9 and 21.5%, in the compliant group, and noncompliant group, respectively. Based on expected FN rates, the respective reduction in the incidence of FN was 51, and 90%. Conclusions. Lack of adherence to institutional guidelines was noticed in G-CSF prescribing. Reasons behind poor compliance with the guidelines must be verified and resolved. Prophylactic G-CSF is effective in reducing the incidence of FN; however, further research in a larger population is warranted to confirm these findings. J Oncol Pharm Practice (2008) 14: 131—138.
Up-regulation of WRN and DNA ligase IIIα in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks
Authors: Sallmyr Annahita , Tomkinson Alan E. , Rassool Feyruz V. 
Published: June 2008

AbstractExpression of oncogenic BCR-ABL in chronic myeloid leukemia (CML) results in increased reactive oxygen species (ROS) that in turn cause increased DNA damage, including DNA double-strand breaks (DSBs). We have previously shown increased error-prone repair of DSBs by nonhomologous end-joining (NHEJ) in CML cells. Recent reports have identified alternative NHEJ pathways that are highly error prone, prompting us to examine the role of the alternative NHEJ pathways in BCR-ABL–positive CML. Importantly, we show that key proteins in the major NHEJ pathway, Artemis and DNA ligase IV, are down-regulated, whereas DNA ligase IIIα, and the protein deleted in Werner syndrome, WRN, are up-regulated. DNA ligase IIIα and WRN form a complex that is recruited to DSBs in CML cells. Furthermore, “knockdown” of either DNA ligase IIIα or WRN leads to increased accumulation of unrepaired DSBs, demonstrating that they contribute to the repair of DSBs. These results indicate that altered DSB repair in CML cells is caused by the increased activity of an alternative NHEJ repair pathway, involving DNA ligase IIIα and WRN. We suggest that, although the repair of ROS-induced DSBs by this pathway contributes to the survival of CML cells, the resultant genomic instability drives disease progression.
Validation of PDGFRβ and c-Src tyrosine kinases as tumor/vessel targets in patients with multiple myeloma: preclinical efficacy of the novel, orally available inhibitor dasatinib
Authors: Coluccia Addolorata Maria Luce , Cirulli Teresa , Neri Paola , Mangieri Domenica , Colanardi Maria Cristina , Gnoni Antonio , Di Renzo Nicola , Dammacco Franco , Tassone Pierfrancesco , Ribatti Domenico , Gambacorti-Passerini Carlo , Vacca Angelo 
Published: June 2008

AbstractInhibition of multiple myeloma (MM) plasma cells in their permissive bone marrow microenvironment represents an attractive strategy for blocking the tumor/vessel growth associated with the disease progression. However, target specificity is an essential aim of this approach. Here, we identified platelet-derived growth factor (PDGF)–receptor beta (PDGFRβ) and pp60c-Src as shared constitutively activated tyrosine-kinases (TKs) in plasma cells and endothelial cells (ECs) isolated from MM patients (MMECs). Our cellular and molecular dissection showed that the PDGF-BB/PDGFRβ kinase axis promoted MM tumor growth and vessel sprouting by activating ERK1/2, AKT, and the transcription of MMEC-released proangiogenic factors, such as vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). Interestingly, pp60c-Src TK-activity was selectively induced by VEGF in MM tumor and ECs, and the use of small-interfering (si)RNAs validated pp60c-Src as a key signaling effector of VEGF loop required for MMEC survival, migration, and angiogenesis. We also assessed the antitumor/vessel activity of dasatinib, a novel orally bioactive PDGFRβ/Src TK-inhibitor that significantly delayed MM tumor growth and angiogenesis in vivo, showing a synergistic cytotoxicity with conventional and novel antimyeloma drugs (ie, melphalan, prednisone, bor-tezomib, and thalidomide). Overall data highlight the biologic and therapeutic relevance of the combined targeting of PDGFRβ/c-Src TKs in MM, providing a framework for future clinical trials.
Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2
Authors: Fang Jing , Menon Madhu , Zhang Diya , Torbett Bruce , Oxburgh Leif , Tschan Mario , Houde Estelle , Wojchowski Don M. 
Published: June 2008

Abstract
The adult erythron is maintained via dynamic modulation of erythroblast survival potentials. Toward identifying novel regulators of this process, murine splenic erythroblasts at 3 developmental stages were prepared, purified and profiled. Stage-to-stage modulated genes were then functionally categorized, with a focus on apoptotic factors. In parallel with BCL-X and NIX, death-associated protein kinase-2 (DAPK2) was substantially up-modulated during late erythropoiesis. Among hematopoietic lineages, DAPK2 was expressed predominantly in erythroid cells. In a Gata1-IE3.9int-DAPK2 transgenic mouse model, effects on steady-state reticulocyte and red blood cell (RBC) levels were limited. During hemolytic anemia, however, erythropoiesis was markedly deficient. Ex vivo ana-lyses revealed heightened apoptosis due to DAPK2 at a Kit−CD71highTer119− stage, together with a subsequent multifold defect in late-stage Kit−CD71highTer119+ cell formation. In UT7epo cells, siRNA knock-down of DAPK2 enhanced survival due to cytokine withdrawal, and DAPK2's phosphorylation and kinase activity also were erythropoietin (EPO)-modulated. DAPK2 therefore comprises a new candidate attenuator of stress erythropoiesis.
Phylogenetic studies of the genus Cebus(Cebidae-Primates) using chromosome painting and G-banding
Authors: Amaral PJS , Finotelo LFM , De Oliveira EHC , Pissinatti A , Nagamachi CY , Pieczarka JC 
Published: June 2008

Abstract

Background
Chromosomal painting, using whole chromosome probes from humans and Saguinus oedipus, was used to establish karyotypic divergence among species of the genus Cebus, including C. olivaceus, C. albifrons, C. apella robustus and C. apella paraguayanus. Cytogenetic studies suggested that the species of this genus have conservative karyotypes, with diploid numbers ranging from 2n = 52 to 2n = 54.

Results
Banding studies revealed morphological divergence among some chromosomes, owing to variations in the size of heterochromatic blocks. This analysis demonstrated that Cebus species have five conserved human associations (i.e., 5/7, 2/16, 10/16, 14/15, 8/18 and 3/21) when compared with the putative ancestral Platyrrhini karyotype.

Conclusion
The autapomorphies 8/15/8 in C. albifrons and 12/15 in C. olivaceus explain the changes in chromosome number from 54 to 52. The association 5/16/7, which has not previously been reported in Platyrrhini, was also found in C. olivaceus. These data corroborate previous FISH results, suggesting that the genus Cebus has a very similar karyotype to the putative ancestral Platyrrhini.
Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials
Authors: Meyer-Lucht Yvonne , Otten Celine , Püttker Thomas , Sommer Simone 
Published: June 2008

Abstract

Background
Research on the genetic architecture and diversity of the MHC has focused mainly on eutherian mammals, birds and fish. So far, studies on model marsupials used in laboratory investigations indicated very little or even no variation in MHC class II genes. However, natural levels of diversity and selection are unknown in marsupials as studies on wild populations are virtually absent. We used two endemic South American mouse opossums, Gracilinanus microtarsus and Marmosops incanus, to investigate characteristic features of MHC selection. This study is the first investigation of MHC selection in free-ranging Neotropical marsupials. In addition, the evolutionary history of MHC lineages within the group of marsupials was examined.

Results

G. microtarsus showed extensive levels of MHC diversity within and among individuals as 47 MHC-DAB alleles and high levels of sequence divergence were detected at a minimum of four loci. Positively selected codon sites were identified, of which most were congruent with human antigen binding sites. The diversity in M. incanus was rather low with only eight observed alleles at presumably two loci. However, these alleles also revealed high sequence divergence. Again, positive selection was identified on specific codon sites, all congruent with human ABS and with positively selected sites observed in G. microtarsus. In a phylogenetic comparison alleles of M. incanus interspersed widely within alleles of G. microtarsus with four alleles being present in both species.

Conclusion
Our investigations revealed extensive MHC class II polymorphism in a natural marsupial population, contrary to previous assumptions. Furthermore, our study confirms for the first time in marsupials the presence of three characteristic features common at MHC loci of eutherian mammals, birds and fish: large allelic sequence divergence, positive selection on specific sites and trans-specific polymorphism.
Transformation of MCF-10A cells by random mutagenesis with frameshift mutagen ICR191: A model for identifying candidate breast-tumor suppressors
Authors: Zientek-Targosz Helena , Kunnev Dimiter , Hawthorn Lesleyann , Venkov Mikhail , Matsui Sei-Ichi , Cheney Richard T , Ionov Yuri 
Published: June 2008

Abstract

Background
Widely accepted somatic mutation theory of carcinogenesis states that mutations in oncogenes and tumor suppressor genes in genomes of somatic cells is the cause of neoplastic transformation. Identifying frequent mutations in cancer cells suggests the involvement of mutant genes in carcinogenesis.

Results
To develop an in vitro model for the analysis of genetic alterations associated with breast carcinogenesis, we used random mutagenesis and selection of human non-tumorigenic immortalized breast epithelial cells MCF-10A in tissue-culture conditions that mimic tumor environment. Random mutations were generated in MCF-10A cells by cultivating them in a tissue-culture medium containing the frameshift-inducing agent ICR191. The first selective condition we used to transform MCF1-10A cells was cultivation in a medium containing mutagen at a concentration that allowed cell replication despite p53 protein accumulation induced by mutagen treatment. The second step of selection was either cell cultivation in a medium with reduced growth-factor supply or in a medium that mimics a hypoxia condition or growing in soft agar. Using mutagenesis and selection, we have generated several independently derived cultures with various degrees of transformation. Gene Identification by Nonsense-mediated mRNA decay Inhibition (GINI) analysis has identified the ICR191-induced frameshift mutations in the TP53, smoothelin, Ras association (RalGDS/AF-6) domain family 6 (RASSF6) and other genes in the transformed MCF-10A cells. The TP53 gene mutations resulting in the loss of protein expression had been found in all independently transformed MCF-10A cultures, which form large progressively growing tumors with sustained angiogenesis in nude mice.

Conclusion
Identifying genes containing bi-allelic ICR191-induced frameshift mutations in the transformed MCF-10A cells generated by random mutagenesis and selection indicates putative breast-tumor suppressors. This can provide a model for studying the role of mutant genes in breast carcinogenesis.
Burkitt's lymphoma of the colon and bronchi: three case reports
Authors: Musallam Khaled M , Taher Ali T , Shamseddine Ali I 
Published: June 2008

Abstract

Introduction
Burkitt's lymphoma is a form of non-Hodgkin's B-cell lymphoma with more than one identifiable variant. The sporadic form most commonly presents with abdominal lymph node involvement.

Case reports
We herein report on three patients from our experience that presented with either endobronchial or colonic Burkitt's lymphoma. Their clinical presentation mimicked that of other syndromes. After confirmatory pathological diagnosis, the patients had complete remission through the use of an optimal treatment protocol.

Conclusion
Our review of the cases and comparable reports warrants careful workup of such presentations to ensure early diagnosis and therapeutic planning of this highly aggressive disease.
Iridium-catalyzed Vinylic C–H Borylation of Cyclic Vinyl Ethers by Bis(pinacolato)diboron
Authors: Kikuchi Takao , Takagi Jun , Ishiyama Tatsuo , Miyaura Norio 
Published: June 2008

Abstract
Vinylic C–H borylation of cyclic vinyl ethers by bis(pinacolato)diboron was effectively catalyzed by iridium complexes comprised of 1/2[Ir(OMe)(cod)]2 and 4,4′-di-tert-butyl-2,2′-bipyridine in hexane or octane to give the corresponding vinylboron compounds in good yields. The reaction of 1,4-dioxene occurred even at room temperature, whereas the reactions of dihydropyran and dihydrofuran derivatives required a temperature above 80 °C. Although dihydropyran and dihydrofuran themselves produced regioisomeric mixtures of α- and β-borylated products, similar substrates possessing substituents at the γ-position selectively underwent borylation at the α-position.
Relative Comparison Method of Rolling Contact Fatigue Performance of Silicon Nitrides by Stepwise Loading Balls-on-Flat Test—A Candidate for Standard Practice for Comparison of RCF Performance
Authors: Kanematsu Wataru 
Published: June 2008

Abstract
We have demonstrated a simple comparison method for rolling contact fatigue (RCF) performance of silicon nitrides using the balls-on-flat RCF test under stepwise loading. The RCF performance was evaluated by the mean effective mechanical input (Min)m which is the product of the mean effective load Pm, calculated from test loads and revolutions during the dwell time for each load, and the number of load cycles. The test materials were six kinds of commercially available silicon nitride, four of bearing-grade silicon nitrides (BG) and two general purpose ones (GP). The minimum test loads were 1 and 0.5 kN for BG and GP, respectively. The load was increased stepwise with each step 107 contact cycles unless failure of the specimen was detected by the acceleration pickup mounted on the loading arm of the testing machine. The balls and test specimen were immersed in mineral oil with kinematic viscosities of 8 mm2/s for BG and 68 mm2/s for GP. A clear distinction in (Min)m was made among the BG, and the GP have lower (Min)m compared to BG, despite small differences in conventional mechanical properties such as Vickers hardness, fracture toughness, and elastic modulus. The results of the balls-on-flat RCF test under constant load for one BG lend support to the hypothesis that the loading history in stepwise loading can be converted to the mean effective load Pm. It is also supported by the fact that classification of failure mechanisms in stepwise loading is similar to that for a constant load of 4 kN, which is close to the mean of Pm of the material. These results imply the viability of a standardized comparison method for RCF performance of bearing-grade silicon nitrides as well as screening for poor performance materials.