bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Apparent Tumor Vascular Permeability from Multiphoton Fluorescence Microscopic Images of P22 Rat Sarcomas In Vivo
Authors: Reyes‐Aldasoro Constantino Carlos , Wilson Ian , Prise Vivien E. , Barber Paul R. , Ameer‐Beg M. , Vojnovic Borivoj , Cunningham Vincent J. , Tozer Gillian M. 
Published: January 2008

ABSTRACTObjective: To develop an image processing‐based method to quantify the rate of extravasation of fluorescent contrast agents from tumor microvessels, and to investigate the effect of the tumor vascular disrupting agent combretastatin A‐4‐P (CA‐4‐P) on apparent tumor vascular permeability to 40 kDa fluorescein isothiocyanate (FITC) labeled dextran.Methods: Extravasation of FITC‐dextran was imaged in 3 dimensions over time within P22 sarcomas growing in dorsal skin flap “window chambers” in BDIX rats using multiphoton fluorescence microscopy. Image processing techniques were used to segment the data into intra‐ and extravascular regions or classes. Quantitative estimates of the tissue influx (vascular leakage) rate constant, Ki, were obtained from the time courses of the fluorescence intensities in the two classes. Apparent permeability, P, was calculated, assuming Ki = PS/V, where S is vascular surface area in tumor volume V.Results: Combining image processing and kinetic analysis algorithms with multiphoton fluorescence microscopy enabled quantification of the rate of tumor vascular leakage, averaged over a large number of vessels. Treatment with CA‐4‐P caused a significant increase in Ki from 1.13 ± 0.33 to 2.59 ± 0.20 (s−1× 10−4; mean ± SEM), equivalent to an increase in P from 12.76 ± 3.36 to 30.94 ± 2.64 (cm s−1× 10−7).Conclusions: A methodology was developed that provided evidence for a CA‐4‐P‐induced increase in tumor macromolecular vascular permeability, likely to be central to its anti‐cancer activity.
Effect of spatial distribution of T-Cells and HIV load on HIV progression
Authors: Graziano Frank M. , Kettoola Samira Y. , Munshower Judy M. , Stapleton Jack T. , Towfic George J. 
Published: January 2008

Abstract
Motivation: We present a spatial-temporal (ST) human immunodeficiency virus (HIV) simulation model to investigate the spatial distribution of viral load and T-cells during HIV progression. The proposed model uses the Finite Element (FE) method to divide a considered infected region into interconnected subregions each containing viral population and T-cells. HIV T-cells and viral load are traced and counted within and between subregions to estimate their effect upon neighboring regions. The objective is to estimate overall ST changes of HIV progression and to study the ST therapeutic effect upon HIV dynamics in spatial and temporal domains. We introduce sub-regional (spatial) parameters of T-cells and viral load production and elimination to estimate the spatial propagation and interaction of HIV dynamics under the influence of a 3TC D4T Reverse Transcriptase Inhibitors (RTI) drug regimen.
Results: In terms of percentage change standard deviation, we show that the average rate per 10 weeks (throughout a 10-year clinical trial) of the ST CD4+ change is 5.35% 1.3 different than that of the CD4+ rate of change in laboratory datasets, and the average rate of change of the ST CD8+ is 4.98% 1.93 different than that of the CD8+ rate of change. The half-life of the ST CD4+ count is 1.68% 3.381 different than the actual half-life of the CD4+ count obtained from laboratory datasets. The distribution of the viral load and T-cells in a considered region tends to cluster during the HIV progression once a threshold of 86–89% viral accumulation is reached.
Availability: Executable code and data libraries are available by contacting the corresponding author.
Implementation: C++ and Java have been used to simulate the suggested model. A Pentium III or higher platform is recommended.
Contact: george.towfic@clarke.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
OutlierD: an R package for outlier detection using quantile regression on mass spectrometry data
Authors: Cho HyungJun , Kim Yang-jin , Jung Hee Jung , Lee Sang-Won , Lee Jae Won 
Published: January 2008

Abstract
Summary: It is important to preprocess high-throughput data generated from mass spectrometry experiments in order to obtain a successful proteomics analysis. Outlier detection is an important preprocessing step. A naive outlier detection approach may miss many true outliers and instead select many non-outliers because of the heterogeneity of the variability observed commonly in high-throughput data. Because of this issue, we developed a outlier detection software program accounting for the heterogeneous variability by utilizing linear, non-linear and non-parametric quantile regression techniques. Our program was developed using the R computer language. As a consequence, it can be used interactively and conveniently in the R environment.
Availability: An R package, OutlierD, is available at the Bioconductor project at http://www.bioconductor.org
Contact: jael@korea.ac.kr
Supplementary information: Supplementary Data are available at Bioinformatics online.
Ontogeny of body size and shape of Antarctic and subantarctic fur seals
Authors: Luque Sebastián P. , Miller Edward H. , Arnould John P.Y. , Chambellant Magaly , Guinet Christophe 
Published: January 2008

Pre- and post-weaning functional demands on body size and shape of mammals are often in conflict, especially in species where weaning involves a change of habitat. Compared with long lactations, brief lactations are expected to be associated with fast rates of development and attainment of adult traits. We describe allometry and growth for several morphological traits in two closely related fur seal species with large differences in lactation duration at a sympatric site. Longitudinal data were collected from Antarctic ( Arctocephalus gazella (Peters, 1875); 120 d lactation) and subantarctic ( Arctocephalus tropicalis (Gray, 1872); 300 d lactation) fur seals. Body mass was similar in neonates of both species, but A. gazella neonates were longer, less voluminous, and had larger foreflippers. The species were similar in rate of preweaning growth in body mass, but growth rates of linear variables were faster for A. gazella pups. Consequently, neonatal differences in body shape increased over lactation, and A. gazella pups approached adult body shape faster than did A. tropicalis pups. Our results indicate that preweaning growth is associated with significant changes in body shape, involving the acquisition of a longer, more slender body with larger foreflippers in A. gazella. These differences suggest that A. gazella pups are physically more mature at approximately 100 d of age (close to weaning age) than A. tropicalis pups of the same age.
Experimental determination of dietary carbon turnover in bovine hair and hoof
Authors: Zazzo A. , Harrison S. M. , Bahar B. , Moloney A. P. , Monahan F. J. , Scrimgeour C. M. , Schmidt O. 
Published: January 2008

Stable isotopes measured in keratinized tissues like hair or hoof have proven to be a useful tool for reconstructing the dietary history of animals with a weekly to daily resolution. Quantitative reconstruction of dietary preferences requires a precise estimate of tissue turnover by means of controlled feeding experiments. We determined the turnover rates of carbon in hoof and tail hair of growing steers ( Bos taurus L., 1758) fed a C3-based diet, followed by a C4-based diet, for 168 d. As with horses, turnover in steer hair was successfully described by a three-pool modelling approach, with apparent half-lives of 1.7, 7.7, and 69.1 d for each of the pools, each contributing 53%, 20%, and 28% of the total signal, respectively. Two pools only were identified in bovine hoof, which recorded the diet switch more slowly than hair with a reduction in the amplitude of short-term isotope changes. We interpreted this result as a sampling artefact and found that the hooves reflected the same pools as the hair if growth geometry is taken into account. The model parameters defined in this study allowed us to quantitatively reconstruct previous diets of steers of different breeds and individual history with a precision of ±1‰.
Niemann-Pick C1-Like 1 Is Required for an LXR Agonist to Raise Plasma HDL Cholesterol in Mice
Authors: Tang Weiqing , Ma Yinyan , Jia Lin , Ioannou Yiannis A. , Davies Joanna P. , Yu Liqing 
Published: January 2008

Objectives—Activation of liver x receptor (LXR) raises plasma HDL-cholesterol (HDL-C) in mice. Interestingly, the LXR agonist GW3965 fails to raise plasma HDL-C in mice lacking intestinal ABCA1, indicating that intestinal ABCA1 plays a predominant role in GW3965-mediated HDL production. How this is coupled to intestinal function remains elusive. Because cholesterol is essential for HDL assembly and directly regulates intestinal ABCA1 expression via activating LXR, we hypothesized that cholesterol absorption, a major function of intestine, modulates LXR-dependent HDL formation.Methods and Results—Mice lacking Niemann-Pick C1-Like 1 (NPC1L1) (L1-KO mice), a gene that is essential for cholesterol absorption, were treated with LXR agonist T0901317 for 7 days. Intriguingly, this treatment failed to significantly raise plasma HDL-C but caused a much greater fecal cholesterol excretion in L1-KO mice. The intestinal ABCA1 mRNA level was about 4-fold lower in L1-KO versus wild-type mice, and increased 3.9-fold and 8.8-fold after T0901317 treatment in wild-type and L1-KO mice, respectively. Hepatic ABCA1 failed to respond to T0901317 in mice of both genotypes, although hepatic mRNAs for many LXR target genes were higher in the T0901317-treated versus untreated wild-type animals.Conclusions—NPC1L1 is required for an LXR agonist to increase plasma HDL-C in mice.
Dongus Tapa – An Iron Age Settlement in the Udabno-Steppe, Eastern Kakheti
Authors: Nieling Jens 
Published: January 2008

AbstractThe article is a preliminary report on an excavation carried out on the Iron Age settlement Dongus Tapa in Kakheti (Eastern Georgia). This fortified settlement existed from the Late Bronze Age till the 7th century BC and lasted longer than the settlements in the Shiraki plain, which end in the same century.
Achaemenian Seals Found in Georgia
Authors: Dzhavakhishvili Ketevan 
Published: January 2008

AbstractIn the article six Achaemenian seals are published, which were found in Georgia. Two of them belong to the seals of the "Oriental Royal Style" according to J. Boardman, the third is an "Occidental Royal Style" seal, one belongs to the "Greco-Oriental" group and two others to the "Bern group". Three of them were found in burials of the Roman period, two in burials of the 4th century BC, while the origin of the last one is unknown.
A dynamic prognostic model to predict survival in post–polycythemia vera myelofibrosis
Authors: Passamonti Francesco , Rumi Elisa , Caramella Marianna , Elena Chiara , Arcaini Luca , Boveri Emanuela , Del Curto Cecilia , Pietra Daniela , Vanelli Laura , Bernasconi Paolo , Pascutto Cristiana , Cazzola Mario , Morra Enrica , Lazzarino Mario 
Published: January 2008

Abstract
Post–polycythemia vera myelofibrosis (post-PV MF) is a late evolution of PV. In 647 patients with PV, we found that leukocytosis leukocyte count > (15 × 109/L) at diagnosis is a risk factor for the evolution of post-PV MF. In a series of 68 patients who developed post-PV MF, median survival was 5.7 years. Hemoglobin level less than 100 g/L (10 g/dL) at diagnosis of post-PV MF was an independent risk factor for survival. The course of post-PV MF, however, is a dynamic process that implies a progressive worsening of clinical parameters. Using a multivariate Cox proportional hazard regression with time-dependent covariates, we found that a dynamic score based on hemoglobin level less than 100 g/L (10 g/dL), platelet count less than 100 × 109/L, and leukocyte count more than 30 × 109/L is useful to predict survival at any time from diagnosis of post-PV MF. The resulting hazard ratio of the score was 4.2 (95% CI: 2.4-7.7; P < .001), meaning a 4.2-fold worsening of survival for each risk factor acquired during follow up. In conclusion, leukocytosis at diagnosis of PV is a risk factor for evolution in post-PV MF. A dynamic score based on hemoglobin level, and platelet and leukocyte count predicts survival at any time from diagnosis of post-PV MF.
Prediction of enzyme function based on 3D templates of evolutionarily important amino acids
Authors: Kristensen David M , Ward R Matthew , Lisewski Andreas Martin , Erdin Serkan , Chen Brian Y , Fofanov Viacheslav Y , Kimmel Marek , Kavraki Lydia E , Lichtarge Olivier 
Published: January 2008

AbstractBackgroundStructural genomics projects such as the Protein Structure Initiative (PSI) yield many new structures, but often these have no known molecular functions. One approach to recover this information is to use3D templates– structure-function motifs that consist of a few functionally critical amino acids and may suggest functional similarity when geometrically matched to other structures. Since experimentally determined functional sites are not common enough to define 3D templates on a large scale, this work tests a computational strategy to select relevant residues for 3D templates.ResultsBased on evolutionary information and heuristics, an Evolutionary Trace Annotation (ETA) pipeline built templates for 98 enzymes, half taken from the PSI, and sought matches in a non-redundant structure database. On average each template matched 2.7 distinct proteins, of which 2.0 share the first three Enzyme Commission digits as the template's enzyme of origin. In many cases (61%) a single most likely function could be predicted as the annotation with the most matches, and in these cases such a plurality vote identified the correct function with 87% accuracy. ETA was also found to be complementary to sequence homology-based annotations. When matches are required to both geometrically match the 3D template and to be sequence homologs found by BLAST or PSI-BLAST, the annotation accuracy is greater than either method alone, especially in the region of lower sequence identity where homology-based annotations are least reliable.ConclusionThese data suggest that knowledge of evolutionarily important residues improves functional annotation among distant enzyme homologs. Since, unlike other 3D template approaches, the ETA method bypasses the need for experimental knowledge of the catalytic mechanism, it should prove a useful, large scale, and general adjunct to combine with other methods to decipher protein function in the structural proteome.
The CMV early enhancer/chicken β actin (CAG) promoter can be used to drive transgene expression during the differentiation of murine embryonic stem cells into vascular progenitors
Authors: Alexopoulou Annika N , Couchman John R , Whiteford James R 
Published: January 2008

Abstract

Background
Mouse embryonic stem cells cultured in vitro have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult.

Results
CCE mouse embryonic stem cells were differentiated on collagen type IV for 4–5 days, Flk1+ mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation of vascular tubes. The activity of the CMV and β-actin promoters was downregulated during selection of stable transfectants and during differentiation to the Flk1 stage, while the CMV immediate enhancer/β-actin promoter in the pCAGIPuro-GFP vector led to 100% of stably transfected undifferentiated and differentiated cells expressing GFP. To further test this system we expressed syndecan-2 and -4 in these cells and demonstrated high levels of transgene expression in both undifferentiated cells and cells differentiated to the Flk1 stage.

Conclusion
Vectors containing the CAG promoter offer a valuable tool for the long term expression of transgenes during stem cell differentiation towards mesoderm, while the CMV and β-actin promoters lead to very poor transgene expression during this process.
A highly sensitive and specific system for large-scale gene expression profiling
Authors: Hu Guohong , Yang Qifeng , Cui Xiangfeng , Yue Gang , Azaro Marco A , Wang Hui-Yun , Li Honghua 
Published: January 2008

Abstract

Background
Rapid progress in the field of gene expression-based molecular network integration has generated strong demand on enhancing the sensitivity and data accuracy of experimental systems. To meet the need, a high-throughput gene profiling system of high specificity and sensitivity has been developed.

Results
By using specially designed primers, the new system amplifies sequences in neighboring exons separated by big introns so that mRNA sequences may be effectively discriminated from other highly related sequences including their genes, unprocessed transcripts, pseudogenes and pseudogene transcripts. Probes used for microarray detection consist of sequences in the two neighboring exons amplified by the primers. In conjunction with a newly developed high-throughput multiplex amplification system and highly simplified experimental procedures, the system can be used to analyze >1,000 mRNA species in a single assay. It may also be used for gene expression profiling of very few (n = 100) or single cells. Highly reproducible results were obtained from duplicate samples with the same number of cells, and from those with a small number (100) and a large number (10,000) of cells. The specificity of the system was demonstrated by comparing results from a breast cancer cell line, MCF-7, and an ovarian cancer cell line, NCI/ADR-RES, and by using genomic DNA as starting material.

Conclusion
Our approach may greatly facilitate the analysis of combinatorial expression of known genes in many important applications, especially when the amount of RNA is limited.
Characterization of a filamentous biofilm community established in a cellulose-fed microbial fuel cell
Authors: Ishii Shun'ichi , Shimoyama Takefumi , Hotta Yasuaki , Watanabe Kazuya 
Published: January 2008

Abstract

Background
Microbial fuel cells (MFCs) are devices that exploit microorganisms to generate electric power from organic matter. Despite the development of efficient MFC reactors, the microbiology of electricity generation remains to be sufficiently understood.

Results
A laboratory-scale two-chamber microbial fuel cell (MFC) was inoculated with rice paddy field soil and fed cellulose as the carbon and energy source. Electricity-generating microorganisms were enriched by subculturing biofilms that attached onto anode electrodes. An electric current of 0.2 mA was generated from the first enrichment culture, and ratios of the major metabolites (e.g., electric current, methane and acetate) became stable after the forth enrichment. In order to investigate the electrogenic microbial community in the anode biofilm, it was morphologically analyzed by electron microscopy, and community members were phylogenetically identified by 16S rRNA gene clone-library analyses. Electron microscopy revealed that filamentous cells and rod-shaped cells with prosthecae-like filamentous appendages were abundantly present in the biofilm. Filamentous cells and appendages were interconnected via thin filaments. The clone library analyses frequently detected phylotypes affiliated with Clostridiales, Chloroflexi, Rhizobiales and Methanobacterium. Fluorescence in-situ hybridization revealed that the Rhizobiales population represented rod-shaped cells with filamentous appendages and constituted over 30% of the total population.

Conclusion
Bacteria affiliated with the Rhizobiales constituted the major population in the cellulose-fed MFC and exhibited unique morphology with filamentous appendages. They are considered to play important roles in the cellulose-degrading electrogenic community.
Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling
Authors: Adam Benoit , Charloteaux Benoit , Beaufays Jerome , Vanhamme Luc , Godfroid Edmond , Brasseur Robert , Lins Laurence 
Published: January 2008

Abstract

Background
Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi.
The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions.

Results
It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein.

Conclusion
By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins.