bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma
Authors: Ria Roberto , Todoerti Katia , Berardi Simona , Coluccia Addolorata Maria Luce , De Luisi Annunziata , Mattioli Michela , Ronchetti Domenica , Morabito Fortunato , Guarini Attilio , Petrucci Maria Teresa , Dammacco Franco , Ribatti Domenico , Neri Antonino , Vacca Angelo 
Published: August 2009

Abstract
Purpose: To determine a “gene/molecular fingerprint” of multiple myeloma endothelial cells and identify vascular mechanisms governing the malignant progression from quiescent monoclonal gammopathy of undetermined significance.
Experimental Design: Comparative gene expression profiling of multiple myeloma endothelial cells and monoclonal gammopathy of undetermined significance endothelial cells with the Affymetrix U133A Arrays was carried out in patients at diagnosis; expression and function of selective vascular markers was validated by real-time reverse transcriptase-PCR, Western blot, and small interfering RNA analyses.
Results: Twenty-two genes were found differentially expressed (14 down-regulated and eight up-regulated) at relatively high stringency in multiple myeloma endothelial cells compared with monoclonal gammopathy of undetermined significance endothelial cells. Functional annotation revealed a role of these genes in the regulation of extracellular matrix formation and bone remodeling, cell adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Validation was focused on six genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3, and SEPW1) not previously found to be functionally correlated to the overangiogenic phenotype of multiple myeloma endothelial cells in active disease. The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype.
Conclusions: The distinct endothelial cell gene expression profiles and vascular phenotypes detected in this study may influence remodeling of the bone marrow microenvironment in patients with active multiple myeloma. A better understanding of the linkage between plasma cells and endothelial cells in multiple myeloma could contribute to the molecular classification of the disease and thus pinpoint selective gene targets for more effective antiangiogenic treatments. (Clin Cancer Res 2009;15(17):5369–78)
Tissue Biomarker Development in a Multicentre Trial Context: a Feasibility Study on the PETACC3 Stage II and III Colon Cancer Adjuvant Treatment Trial
Authors: Bosman Fred T. , Yan Pu , Tejpar Sabine , Fiocca Roberto , Van Cutsem Eric , Kennedy Richard D. , Dietrich Daniel , Roth Arnaud 
Published: August 2009

Abstract
Purpose: We evaluated the feasibility of biomarker development in the context of multicenter clinical trials.
Experimental Design: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments.
Results: Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments.
Conclusions: Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials. (Clin Cancer Res 2009;15(17):5528–33)
Sensitivity of Monthly Convective Precipitation to Environmental Conditions
Authors: Myoung Boksoon , Nielsen-Gammon John W. 
Published: August 2009

Abstract
Identifying dynamical and physical mechanisms controlling variability of convective precipitation is critical for predicting intraseasonal and longer-term changes in warm-season precipitation and convectively driven large-scale circulations. On a monthly basis, the relationship of convective instability with precipitation is examined to investigate the modulation of convective instability on precipitation using the Global Historical Climatology Network (GHCN) and NCEP–NCAR reanalysis for 1948–2003. Three convective parameters—convective inhibition (CIN), precipitable water (PW), and convective available potential energy (CAPE)—are examined. A lifted index and a difference between low-tropospheric temperature and surface dewpoint are used as proxies of CAPE and CIN, respectively.
A simple correlation analysis between the convective parameters and the reanalysis precipitation revealed that the most significant convective parameter in the variability of monthly mean precipitation varies by regions and seasons. With respect to region, CIN is tightly coupled with precipitation over summer continents in the Northern Hemisphere and Australia, while PW or CAPE is tightly coupled with precipitation over tropical oceans. With respect to seasons, the identity of the most significant convective parameter tends to be consistent across seasons over the oceans, while it varies by season in Africa and South America. Results from GHCN precipitation data are broadly consistent with reanalysis data where GHCN data exist, except in some tropical areas where correlations are much stronger (and sometimes signed differently) with reanalysis precipitation than with GHCN precipitation.
Effect of Atlantic Meridional Overturning Circulation Changes on Tropical Atlantic Sea Surface Temperature Variability: A 2½-Layer Reduced-Gravity Ocean Model Study
Authors: Wen Caihong , Chang Ping , Saravanan Ramalingam 
Published: August 2009

Abstract
Previous coupled climate model simulations reveal that a dipole-like SST pattern with cooler (warmer) temperature over the north (south) tropical Atlantic emerges in response to a slowdown of the Atlantic meridional overturning circulation (AMOC). Using a 2½-layer reduced-gravity ocean model, a systematic investigation into oceanic processes controlling the tropical Atlantic sea surface temperature (SST) response to AMOC changes by varying the strength of northward mass transport at the open boundaries was conducted. It is found that the North Brazil Current (NBC) reverses its direction in response to a shutdown of the AMOC. Such a circulation change causes a decrease in upper equatorial ocean stratification and warming in the Gulf of Guinea and off the coast of Africa. These findings point to the importance of oceanic dynamics in the equatorial SST response to AMOC changes. Sensitivity experiments further show that the SST response relates nonlinearly to AMOC changes. The strength of the SST response increases dramatically when the AMOC strength falls below a threshold value. This nonlinear threshold behavior depends on the position of a subsurface temperature gradient forming along the boundary between the northern subtropical gyre and the tropical gyre that interacts with the western boundary current. The analysis suggests that, in order for the oceanic dynamics to have a dominant influence on tropical Atlantic SST in response to AMOC changes, two conditions must be satisfied: 1) the AMOC must weaken substantially so that the NBC flows equatorward, permitting water mass exchange between the northern subtropical and tropical gyres, and 2) the subsurface temperature front must be located in an optimal location where subsurface temperature anomalies induced by AMOC change are able to enter the equatorial zone.
Effects of Convective Processes on GCM Simulations of the Madden–Julian Oscillation
Authors: Deng Liping , Wu Xiaoqing 
Published: August 2009

Abstract
Weak temporal variability in tropical climates such as the Madden–Julian oscillation (MJO) is one of major deficiencies in general circulation models (GCMs). The uncertainties in the representation of convection and cloud processes are responsible for these deficiencies. With the improvement made to the convection scheme, the Iowa State University (ISU) GCM, which is based on a version of the NCAR Community Climate Model, is able to simulate many features of MJO as revealed by observations. In this study, four 10-yr (1979–88) ISU GCM simulations with observed sea surface temperatures are analyzed and compared to examine the effects of the revised convection closure, convection trigger condition, and convective momentum transport (CMT) on the MJO simulations. The modifications made in the convection scheme improve the simulations of amplitude, spatial distribution, eastward propagation, and horizontal and vertical structures, especially for the coherent feature of eastward-propagating convection and the precursor sign of convective center. The revised convection closure plays a key role in the improvement of the eastward propagation of MJO. The convection trigger helps produce less frequent but more vigorous moist convection and enhance the amplitude of the MJO signal. The inclusion of CMT results in a more coherent structure for the MJO deep convective center and its corresponding atmospheric variances.
Vertical Covariance Localization for Satellite Radiances in Ensemble Kalman Filters
Authors: Campbell William F. , Bishop Craig H. , Hodyss Daniel 
Published: August 2009

AbstractA widely used observation space covariance localization method is shown to adversely affect satellite radiance assimilation in ensemble Kalman filters (EnKFs) when compared to model space covariance localization. The two principal problems are that distance and location are not well defined for integrated measurements, and that neighboring satellite channels typically have broad, overlapping weighting functions, which produce true, nonzero correlations that localization in radiance space can incorrectly eliminate. The limitations of the method are illustrated in a 1D conceptual model, consisting of three vertical levels and a two-channel satellite instrument. A more realistic 1D model is subsequently tested, using the 30 vertical levels from the Navy Operational Global Atmospheric Prediction System (NOGAPS), the Advanced Microwave Sounding Unit A (AMSU-A) weighting functions for channels 6–11, and the observation error variance and forecast error covariance from the NRL Atmospheric Variational Data Assimilation System (NAVDAS). Analyses from EnKFs using radiance space localization are compared with analyses from raw EnKFs, EnKFs using model space localization, and the optimal analyses using the NAVDAS forecast error covariance as a proxy for the true forecast error covariance. As measured by mean analysis error variance reduction, radiance space localization is inferior to model space localization for every ensemble size and meaningful observation error variance tested. Furthermore, given as many satellite channels as vertical levels, radiance space localization cannot recover the true temperature state with perfect observations, whereas model space localization can.
Multiple sclerosis and neurofibromatosis type 1: report of seven patients from Iran
Authors: Etemadifar M , Fatehi F , Sahraian MA , Borhanihaghighi A , Ardestani PM , Kaji-Esfahani M , Maghzi AH 
Published: August 2009

Introduction Co-occurrence of multiple sclerosis (MS) and neurofibromatosis type 1 (NF1) is rare. Case reports In this study, we describe the clinical and neuroimaging features of seven patients with NF1 and MS. In our patients, six patients with MS were women, in all of them history of NF1 existed. Three of our patients had primary progressive, one had secondary progressive MS, and three relapsing–remitting MS. Optic neuritis as presenting symptoms was seen in three patients, and motor manifestation as presenting symptom was observed in three patients. The risk of having both NF1 and MS seemed to be higher than would be expected based on the prevalence rates of the two diseases in the general population. Conclusion The findings of this study suggest a possible casual relationship between MS and NF1, indicating higher risk of MS among patients with NF1.
Sjögren’s syndrome myelopathy: spinal cord involvement in Sjögren’s syndrome might be a manifestation of neuromyelitis optica
Authors: Kim SM , Waters P , Vincent A , Kim SY , Kim HJ , Hong YH , Park KS , Min JH , Sung JJ , Lee KW 
Published: August 2009

Objective To evaluate clinical characteristics, aquaporin (AQP)-4 antibody results, and probability of developing symptoms of neuromyelitis optica (NMO) in patients with Sjögren’s syndrome myelopathy (SSM). Methods We identified eight patients with spinal cord involvement from 112 patients with Sjögren’s syndrome (SS) referred to the neurology department. The clinical characteristics and AQP-4 antibody status, based on immunoprecipitation of EGFP-tagged AQP-4, of the patients with SSM were assessed. Results All patients with SSM had extensive spinal cord lesions, high mean annual relapse rates, and poor response to steroid treatment. Of the eight patients with SSM, seven patients satisfied the revised diagnostic criteria for NMO or showed positive results from AQP-4 antibody testing; one patient had incomplete follow-up. The clinical manifestations and AQP-4 autoantibody status of patients with SSM did not differ significantly from those of NMO patients without SS. Conclusion All patients with SSM had poor prognosis with high mean annual relapse rates, and most seemed to have the clinical and immunological characteristics of NMO. Early aggressive immune therapies should be considered in patients with SSM irrespective of the presence or absence of optic neuritis.
Overexpression of Rheb2 enhances mouse hematopoietic progenitor cell growth while impairing stem cell repopulation
Authors: Campbell Timothy B. , Basu Sunanda , Hangoc Giao , Tao Wen , Broxmeyer Hal E. 
Published: August 2009

Abstract
Molecular mechanisms preserving hematopoietic stem cell (HSC) self-renewal by maintaining a balance between proliferation, differentiation, and other processes are not fully understood. Hyperactivation of the mammalian target of rapamycin (mTOR) pathway, causing sustained proliferative signals, can lead to exhaustion of HSC repopulating ability. We examined the role of the novel ras gene Rheb2, an activator of the mTOR kinase, in colony-forming ability, survival, and repopulation of immature mouse hematopoietic cells. In a cell line model of mouse hematopoietic progenitor cells (HPCs), we found enhanced proliferation and mTOR signaling in cells overexpressing Rheb2. In addition, overexpression of Rheb2 enhanced colony-forming ability and survival of primary mouse bone marrow HPCs. Expansion of phenotypic HSCs in vitro was enhanced by Rheb2 overexpression. Consistent with these findings, Rheb2 overexpression transiently expanded phenotypically defined immature hematopoietic cells after in vivo transplantation; however, these Rheb2-transduced cells were significantly impaired in overall repopulation of primary and secondary congenic transplantation recipients. Our findings suggest that HPCs and HSCs behave differently in response to growth-promoting signals stimulated by Rheb2. These results may have value in elucidating mechanisms controlling the balance between proliferation and repopulating ability, a finding of importance in clinical uses of HPCs/HSCs.
Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells
Authors: Seiler Till , Woelfle Manuela , Yancopoulos Sophia , Catera Rosa , Li Wentian , Hatzi Katerina , Moreno Carol , Torres Marcela , Paul Santanu , Dohner Hartmut , Stilgenbauer Stephan , Kaufman Matthew S. , Kolitz Jonathan E. , Allen Steven L. , Rai Kanti R. , Chu Charles C. , Chiorazzi Nicholas 
Published: August 2009

AbstractDespite a wealth of information about the structure of surface membrane immunoglobulin (smIg) on chronic lymphocytic leukemia (CLL) cells, little is known about epitopes reacting with their binding sites. Probing phage-displayed peptide libraries, we identified and characterized mimetopes for Igs of 4 patients with IGHV mutated CLL (M-CLL) and 4 with IGHV unmutated CLL (U-CLL). Six of these mAbs were representatives of stereotyped B-cell receptors characteristic of CLL. We found that mimetic epitopes for U- and M-CLL Igs differed significantly. M-CLL–derived peptides exhibited better amino acid motifs, were more similar to each other, aligned more easily, and formed tighter clusters than U-CLL–derived peptides. Mono-, oligo-, and polyreactivity of peptides correlated with structural changes within antigen-binding sites of selecting M-CLL mAbs. Although M-CLL–isolated peptides and certain U-CLL mAbs bound more effectively to the selecting mAb, others were not as specific, reacting with M-CLL and U-CLL mAbs; these data suggest that in vivo structurally diverse epitopes could bind smIgs of distinct CLL clones, thereby altering survival and growth. Finally, an M-CLL–derived peptide inhibited, in a dose-dependent manner, binding of its homologous mAb to human B lymphocytes; therefore peptides that inhibit or alter the consequences of antigen-smIg interactions may represent therapeutic modalities in CLL.
Histone hyperacetylation within the β-globin locus is context-dependent and precedes high-level gene expression
Authors: Fromm George , de Vries Christina , Byron Rachel , Fields Jennifer , Fiering Steven , Groudine Mark , Bender M. A. , Palis James , Bulger Michael 
Published: August 2009

Abstract
Active gene promoters are associated with covalent histone modifications, such as hyperacetylation, which can modulate chromatin structure and stabilize binding of transcription factors that recognize these modifications. At the β-globin locus and several other loci, however, histone hyperacetylation extends beyond the promoter, over tens of kilobases; we term such patterns of histone modifications “hyperacetylated domains.” Little is known of either the mechanism by which these domains form or their function. Here, we show that domain formation within the murine β-globin locus occurs before either high-level gene expression or erythroid commitment. Analysis of β-globin alleles harboring deletions of promoters or the locus control region demonstrates that these sequences are not required for domain formation, suggesting the existence of additional regulatory sequences within the locus. Deletion of embryonic globin gene promoters, however, resulted in the formation of a hyperacetylated domain over these genes in definitive erythroid cells, where they are otherwise inactive. Finally, sequences within β-globin domains exhibit hyperacetylation in a context-dependent manner, and domains are maintained when transcriptional elongation is inhibited. These data narrow the range of possible mechanisms by which hyperacetylated domains form.
Ultra-Structure database design methodology for managing systems biology data and analyses
Authors: Maier Christopher W , Long Jeffrey G , Hemminger Bradley M , Giddings Morgan C 
Published: August 2009

AbstractBackgroundModern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping).ResultsWe transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research.ConclusionWe find Ultra-Structure offers substantial benefits for biological information systems, the largest being the integration of diverse information sources into a common framework. This facilitates systems biology research by integrating data from disparate high-throughput techniques. It also enables us to readily incorporate new data types, sources, and domain knowledge with no change to the database structure or associated computer code. Ultra-Structure may be a significant step towards solving the hard problem of data management and integration in the systems biology era.
Limitations in SELDI-TOF MS whole serum proteomic profiling with IMAC surface to specifically detect colorectal cancer
Authors: Wang Qi , Shen Jing , Li Zhen-fu , Jie Jian-zheng , Wang Wen-yue , Wang Jin , Zhang Zhong-tao , Li Zhi-xia , Yan Li , Gu Jin 
Published: August 2009

Abstract

Background
Surface enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) analysis on serum samples was reported to be able to detect colorectal cancer (CRC) from normal or control patients. We carried out a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify CRC.

Methods
A retrospective cohort of 338 serum samples including 154 CRCs, 67 control cancers and 117 non-cancerous conditions was profiled using SELDI-TOF-MS.

Results
No CRC "specific" classifier was found. However, a classifier consisting of two protein peaks separates cancer from non-cancerous conditions with high accuracy.

Conclusion
In this study, the SELDI-TOF-MS-based protein expression profiling approach did not perform to identify CRC. However, this technique is promising in distinguishing patients with cancer from a non-cancerous population; it may be useful for monitoring recurrence of CRC after treatment.