bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proinflammatory CD4+CD45RBhi Lymphocytes Promote Mammary and Intestinal Carcinogenesis in Apc
Min/+ Mice
Authors: Rao Varada P. , Poutahidis Theofilos , Ge Zhongming , Nambiar Prashant R. , Horwitz Bruce H. , Fox James G. , Erdman Susan E. 
Published: January 2006

Abstract
Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to be a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4+CD45RBhi (TE) cells to induce inflammatory bowel disease (IBD) in mice, to investigate roles of inflammation on carcinogenesis in the ApcMin/+ mouse model of intestinal polyposis. We find that transfer of TE cells significantly increases adenoma multiplicity and features of malignancy in recipient ApcMin/+ mice. Surprisingly, we find that female ApcMin/+ recipients of TE cells also rapidly develop mammary tumors. Both intestinal polyposis and mammary adenocarcinoma are abolished by cotransfer of anti-inflammatory CD4+CD45RBlo regulatory lymphocytes or by neutralization of key proinflammatory cytokine tumor necrosis factor-α. Lastly, down-regulation of cyclooxygenase-2 and c-Myc expression is observed coincident with tumor regression. These findings define a novel mouse model of inflammation-driven mammary carcinoma and suggest that epithelial carcinogenesis can be mitigated by anti-inflammatory cells and cytokines known to regulate IBD in humans and mice. (Cancer Res 2006; 66(1): 57-61)
Eco‐efficiency Trends in the UK Steel and Aluminum Industries
Authors: Dahlström Kristina , Ekins Paul 
Published: January 2006

SummaryMeasures of eco‐efficiency—broadly understood as “getting more from less”—often include an economic and an environmental variable. The latter is often seen as the more problematic variable, particularly when used in relation to impacts of public concern. But an analysis of resource and value trends in the U.K. steel and aluminum industries over the last 30 yr showed that there are significant problems associated with using economic variables in measures of eco‐efficiency at the sectoral level.The research found that the U.K. steel and aluminum industries have improved the effectiveness with which they use natural resources, but that this has been accompanied by a decline in the economic output (value added) per unit of material or energy consumed. These seemingly contradictory results can be explained by the fall in the price of metals in real terms, and by the competitive pressures that necessitate the cutting of production costs and indirectly lead to a fall in the measure of economic output of the relevant industry.The research also suggests a logical terminology to bring consistency and coherence to the broad field of eco‐efficiency indicators, with an important distinction made between measures that examine the value output per unit of physical input, and measures that examine the physical output per unit of physical input. Both these types of indicators are important, as they highlight different aspects of eco‐efficiency.
Eulerian Available Energetics in Moist Atmospheres
Authors: Bannon Peter R. 
Published: January 2006

Abstract
A new derivation of local available energy for a compressible, multicomponent fluid that allows for frictional, diabatic, and chemical (e.g., phase changes) processes is presented. The available energy is defined relative to an arbitrary isothermal atmosphere in hydrostatic balance with uniform total chemical potentials. It is shown that the available energy can be divided into available potential, available elastic, and available chemical energies. Each is shown to be positive definite.
The general formulation is applied to the specific case of an idealized, moist, atmospheric sounding with liquid water and ice. The available energy is dominated by available potential energy in the troposphere but available elastic energy dominates in the upper stratosphere. The available chemical energy is significant in the lower troposphere where it dominates the available elastic energy. The total available energy increases with increasing water content.
Variability in the Southerly Flow into the Eastern Pacific ITCZ*
Authors: de Szoeke Simon P. , Bretherton Christopher S. 
Published: January 2006

Abstract
During boreal summer and fall, there is a strong southerly boundary layer flow across the equator into the east Pacific intertropical convergence zone (ITCZ). The modulation of this flow on synoptic to seasonal time scales is studied using an index of meridional pressure difference between the equator and the ITCZ along 95°W. Two complementary datasets from the East Pacific Investigation of Climate (EPIC) are used to study eastern Pacific variability. Daily measurements of sea level pressure (SLP) from Tropical Atmosphere Ocean (TOA) array buoys from May to November 2001 provide temporal coverage, and eight flights by a C-130 aircraft during September to October 2001 document the associated modulation of lower tropospheric vertical structure.
The principal mode of variability of the perturbation SLP along 95°W from 1°S to 12°N, derived by principal component analysis from either the eight flights (PC1C-130) or from daily TAO buoy observations (PC1), explains 77% of the meridional pressure gradient variability. The pressure anomalies at 1.6 km are similar to those at the surface. The time series of the first mode of the TAO observations shows that most of the variance is in the 2–7-day range. Low pressure at 12°N is associated with southerly and westerly surface wind anomalies, and enhanced precipitation in the ITCZ. The depth of ITCZ convection is more strongly correlated to meridional wind above the planetary boundary layer (PBL) than to meridional wind within the PBL. There is little correlation of PBL meridional flow across the equator with ITCZ convection.
Regression of PC1C-130 against the 95°W cross sections observed by dropwinsondes released during the eight C-130 flights shows correlations of westerlies to positive PC1C-130 (low pressure at 12°N). Between the equator and 4°N, statistically significant northerlies just above the PBL at 1–2-km height and southerlies at 4 km are correlated with negative PC1C-130, having high SLP at 12°N, an anomalously weak meridional SLP gradient, and suppressed convection in the ITCZ.
PC1 is bandpass filtered and correlated with reanalysis fields to identify the structures that modulate meridional pressure gradients along 95°W. Most of the variability at periods less than 15 days is related to easterly waves. Seasonal trends in PC1 during May–October 2001 reflect the seasonal evolution of the sea and land surface temperatures. After the seasonal trend is removed, a geostrophic westerly jet at 12°N—probably related to the Madden–Julian oscillation—dominates PC1 variability on time scales longer than 15 days.
Fetomaternal cross talk in the placental vascular bed: control of coagulation by trophoblast cells
Authors: Sood Rashmi , Kalloway Shawn , Mast Alan E. , Hillard Cecilia J. , Weiler Hartmut 
Published: December 2005

AbstractHumans and rodents exhibit a peculiar type of placentation in which zygote-derived trophoblast cells, rather than endothelial cells, line the terminal maternal vascular space. This peculiar aspect of the placental vasculature raises important questions about the relative contribution of fetal and maternal factors in the local control of hemostasis in the placenta and how these might determine the phenotypic expression of thrombophilia-associated complications of pregnancy. Using genomewide expression analysis, we identify a panel of genes that determine the ability of fetal trophoblast cells to regulate hemostasis at the fetomaternal interface. We show that spontaneous differentiation of trophoblast stem cells is associated with the acquisition of an endothelial cell–like thromboregulatory gene expression program. This program is developmentally regulated and conserved between mice and humans. We further show that trophoblast cells sense, via the expression of protease activated receptors, the presence of activated coagulation factors. Engagement of these receptors results in cell-type specific changes in gene expression. Our observations define candidate fetal genes that are potential risk modifiers of maternal thrombophilia-associated pregnancy complications and provide evidence that coagulation activation at the fetomaternal interface can affect trophoblast physiology altering placental function in the absence of frank thrombosis.
Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT)
Authors: Dhabuwala Atul , Lamerton Prue , Stubbs Richard S 
Published: December 2005

Abstract

Background
SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of 90Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of 90Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response.

Methods
58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT.

Results
Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r2 = 0.004). CT responses after 3 months were not different in the 2 Groups.

Conclusion
The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of 90Y microspheres used may be greater than is necessary.
HIV Prevalence among Aboriginal British Columbians
Authors: Hogg Robert S , Strathdee Steffanie , Kerr Thomas , Wood Evan , Remis Robert 
Published: December 2005

Abstract

Context
There is considerable concern about the spread of HIV disease among Aboriginal peoples in British Columbia.

Objective
To estimate the number of Aboriginal British Columbians infected with HIV.

Design and setting
A population-based analysis of Aboriginal men and women in British Columbia, Canada from 1980 to 2001.

Participants
Epidemic curves were fit for gay and bisexual men, injection drug users, men and women aged 15 to 49 years and persons over 50 years of age.

Main outcome measures
HIV prevalence for the total Aboriginal population was modeled using the UNAIDS/WHO Estimation and Projection Package (EPP). Monte Carlo simulation was used to estimate potential number infected for select transmission group in 2001.

Results
A total of 170,025 Aboriginals resided in British Columbia in 2001, of whom 69% were 15 years and older. Of these 1,691 (range 1,479 – 1,955) men and women aged 15 years and over were living with HIV with overall prevalence ranging from 1.26% to 1.66%. The majority of the persons infected were men. Injection drug users (range 1,202 – 1,744) and gay and bisexual men (range 145, 232) contributed the greatest number of infections. Few persons infected were from low risk populations.

Conclusion
More than 1 in every 100 Aboriginals aged 15 years and over was living with HIV in 2001. Culturally appropriate approaches are needed to tailor effective HIV interventions to this community.
SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling
Authors: Souza Vinicius , Dong Yan Bin , Zhou H Sam , Zacharias Wolfgang , McMasters Kelly M 
Published: December 2005

Abstract

Background
The goal of this study was to evaluate changes in gene expression in SW-620 cells in response to SN-38 in order to further elucidate the mechanisms by which SN-38 causes apoptosis and cell cycle arrest.

Methods
We used a quantitative gene expression microarray assay to identify the genes regulated by SN-38 treatment in colon cancer cells and confirmed our results with RT-PCR. By gene expression profiling, we first screened a proprietary list of about 22,000 genes.

Results
Treatment with SN-38 cells resulted in two-fold or greater alteration in the level of expression of 192 genes compared to control treatment. Most of the affected genes were not known to be responsive to SN-38 prior to this study. SN-38 treatment of these cells was found to affect the expression of various genes involved in DNA replication, transcription, signal transduction, growth factors, cell cycle regulation, and apoptosis, as well as other genes with unknown function. Changes in expression of 14 genes were confirmed by quantitative real-time polymerase chain reaction (RT-PCR).

Conclusion
This study leads to an increased understanding of the biochemical pathways involved in SN-38-induced apoptosis and possibly to the identification of new therapeutic targets.
Characterization of a monoclonal antibody with specificity for holo-transcobalamin
Authors: Orning Lars , Rian Anne , Campbell Andrew , Brady Jeff , Fedosov Sergey N , Bramlage Birgit , Thompson Keith , Quadros Edward V 
Published: January 2006

Abstract

Background
Holotranscobalamin, cobalamin-saturated transcobalamin, is the minor fraction of circulating cobalamin (vitamin B12), which is available for cellular uptake and hence is physiologically relevant. Currently, no method allows simple, direct quantification of holotranscobalamin. We now report on the identification and characterization of a monoclonal antibody with a unique specificity for holotranscobalamin.

Methods
The specificity and affinity of the monoclonal antibodies were determined using surface plasmon resonance and recombinant transcobalamin as well as by immobilizing the antibodies on magnetic microspheres and using native transcobalamin in serum. The epitope of the holotranscobalamin specific antibody was identified using phage display and comparison to a de novo generated three-dimensional model of transcobalamin using the program Rosetta. A direct assay for holotrnscobalamin in the ELISA format was developed using the specific antibody and compared to the commercial assay HoloTC RIA.

Results
An antibody exhibiting >100-fold specificity for holotranscobalamin over apotranscobalamin was identified. The affinity but not the specificity varied inversely with ionic strength and pH, indicating importance of electrostatic interactions. The epitope was discontinuous and epitope mapping of the antibody by phage display identified two similar motifs with no direct sequence similarity to transcobalamin. A comparison of the motifs with a de novo generated three-dimensional model of transcobalamin identified two structures in the N-terminal part of transcobalamin that resembled the motif. Using this antibody an ELISA based prototype assay was developed and compared to the only available commercial assay for measuring holotranscobalamin, HoloTC RIA.

Conclusion
The identified antibody possesses a unique specificity for holotranscobalamin and can be used to develop a direct assay for the quantification of holotranscobalamin.
A general formulation for a one-sided group sequential design
Authors: Moser Barry K , George Stephen L 
Published: December 2005

Background A major contribution to the statistical literature on group sequential designs was provided by Pampallona and Tsiatis who developed closed form functions that can be used to iteratively calculate the boundary points of a family of popular group sequential designs [1]. A related area of interest is the use of conditional probability calculations to make interim decisions in stochastic curtailment procedures. Purpose The purpose of the paper is to develop group sequential designs based on conditional probabilities, to compare our results to the general closed form family of designs developed by Pampallona and Tsiatis, and to relate these to commonly used stochastic curtailment procedures. Methods The problem and its solution are formulated and derived mathematically. A graphical interpretation of the results provides the reader with an alternative mechanism to understand the results and their significance. Results One-sided group sequential design boundary points, as closed form functions, are derived from conditional probability statements. These conditional probability statements can be interpreted as the probability, at the final analysis, of reversing the conclusion reached at an interim state. Under mild constraints, these boundary points are identical to the Pampallona and Tsiatis boundary points. At any interim stage when a boundary point is attained or surpassed we suggest a graphical approach to examine the conditional probability of reversing the interim decision at the final stage versus a range of possible parameter values. For stochastic curtailment procedures, we recommend relaxing (increasing) the conditional probability levels to at least 0.50 so that early stopping is at least as likely as for the O'Brien-Fleming procedure. Limitations The results are limited to one-sided group sequential designs. Conclusions Conditional probabilities of reversing interim decisions provides a useful concept to develop group sequential designs and to evaluate stochastic curtailment procedures.
Monitoring event times in early phase clinical trials: some practical issues
Authors: Thall Peter F , Wooten Leiko H , Tannir Nizar M 
Published: December 2005

Background In many early phase clinical trials it is scientifically inappropriate or logistically infeasible to characterize patient outcome as a binary variable. In such settings, it often is more natural to construct early stopping rules based on time-to-event variables. This type of design may involve a variety of complications, however. Purpose The purpose of this paper is to illustrate by example how one may deal with various complications that may arise when monitoring time-to-event outcomes in an early phase clinical trial. Methods We present a series of Bayesian designs for a phase II clinical trial in kidney cancer. Each design includes a procedure for monitoring the times to a severe adverse event, disease progression and death. The first design, which is the simplest, is based on the time to failure, defined as any of the three events, assuming exponentially distributed failure times with an inverse gamma prior on the mean. This design is compared by simulation to the CMAP design (Cheung and Thall, Biometrics, 2002; 58: 89–97). The model and monitoring procedure are then extended successively to accommodate several common practical complications, and we also study the method's robustness. Results Our simulations show that 1) one may apply the monitoring rule periodically, rather than continuously, without a substantive degradation of the design's reliability; 2) it is very important to account for interval censoring due to periodic evaluation of disease status; 3) it is important to account for the effect of disease progression on the subsequent death rate; 4) conducting a randomized trial presents little additional difficulty and provides unbiased comparisons; and 5) the exponential-inverse gamma model is surprisingly robust in most cases. Limitations The methods discussed here do not account for patient heterogeneity. This is an important but complex issue that may be dealt with by extending the models and methods given here to accommodate patient covariates and treatment-covariate interaction. Conclusions Bayesian procedures for monitoring time-to-event outcomes offer a practical way to conduct a variety of early phase trials. Considerable care must be given, however, to modeling the important aspects of the trial at hand, and to calibrating the prior and the design parameters to ensure that the design will have good operating characteristics.
Identifying methodologies in the assessment of treatment effects on the repeated occurrences of hot flashes in postmenopausal women
Authors: He Weili , Deng Weiping 
Published: December 2005

Background Two methods that are commonly used in most clinical trials for evaluating the effect of treatment on hot flashes are frequency only and severity score methods. However, in these crude methods, composite recurrent hot flash data on a patient are reduced to a one-dimensional summary measure, an approach which may not be optimal. In addition, the duration of a hot flash event provides additional information, which is not accounted for in the two methods mentioned above. Purpose We propose two new methods in the analysis of hot flash data in this paper. Methods The first method utilizes a generalization of the continuation ratio model to model the severity of a hot flash event. The model accounts for individual random effects and dependence of recurrent events within an individual. The other method that accounts for the duration of a hot flash event is a 3-Dimensional (3D) score method, which incorporates hot flash information on frequency, severity, and duration. Results Simulation studies were conducted to evaluate the properties of our proposed methods. The results indicate that our proposed generalized continuation ratio model has appreciably high power in detecting small treatment effects on severity compared with the two commonly used methods. The proposed 3D score, on the other hand, is sensitive in detecting treatment effects on both frequency and duration, but has low power in detecting treatment effects on severity alone. Conclusions Our proposed generalized continuation ratio model approach provides a valuable and powerful alternative to the two commonly used methods in the analysis of treatment effects on hot flash severity. Our proposed 3D score method incorporates the additional information hot flash duration provides, and is another analysis option for the practitioners to employ.