bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordination of DNA Mismatch Repair and Base Excision Repair Processing of Chemotherapy and Radiation Damage for Targeting Resistant Cancers
Authors: Kinsella Timothy J. 
Published: February 2009

Abstract
DNA damage processing by mismatch repair (MMR) and/or base excision repair (BER) can determine the therapeutic index following treatment of human cancers using radiation therapy and several classes of chemotherapy drugs. Over the last decade, basic and translational cancer research in DNA repair has led to an increased understanding of how these two DNA repair pathways can modify cytotoxicity to chemotherapy and/or ionizing radiation treatments in both normal and malignant tissues. This Molecular Pathways article provides an overview of the current understanding of mechanisms involved in MMR and BER damage processing, including insights into possible coordination of these two DNA repair pathways after chemotherapy and/or ionizing radiation damage. It also introduces principles of systems biology that have been applied to better understand the complexities and coordination of MMR and BER in processing these DNA damages. Finally, it highlights novel therapeutic approaches to target resistant (or DNA damage tolerant) human cancers using chemical and molecular modifiers of chemotherapy and/or ionizing radiation including poly (ADP-ribose) polymerase inhibitors, methoxyamine and iododeoxyuridine (and the prodrug, 5-iodo-2-pyrimidinone-2'-deoxyribose).
Systemic Administration of a Conditionally Replicating Adenovirus, Targeted to Angiogenesis, Reduced Lung Metastases Burden in Cotton Rats
Authors: Peled Michael , Shaish Aviv , Katav Avi , Greenberger Shoshana , Barshack Iris , Tal Reshef , Bangio Livnat , Breitbart Eyal , Harats Dror 
Published: February 2009

AbstractPurpose: Angiogenesis is an essential process for solid tumor development. To interfere with angiogenesis, AdPPE3x-E1, an adenovirus that is transcriptionally targeted to replicate in angiogenic endothelial cells, was constructed, by replacing the E1 promoter with the modified preproendothelin-1 promoter, PPE-1-3x, previously shown to induce specific transcription in angiogenic endothelial cells.Experimental Design: The specificity of AdPPE3x-E1 to endothelial cells was shown by quantitative PCR and immunostaining, and its antiangiogenic effect was evaluated in Matrigel models. The in vivo efficacy of AdPPE3x-E1 was also tested in a cotton rat lung metastases model.Results: The replication rate of AdPPE3x-E1 in endothelial cells was similar to that of AdCMV-E1, a nonselective replicating adenovector, but the replication rate was reduced up to 60-fold in nonendothelial cells. Moreover, AdPPE3x-E1 reduced endothelial cell viability by 90% whereas nonendothelial cells were not affected. In in vitro and in vivo Matrigel models, endothelial cells infected with AdPPE3x-E1 did not develop capillary-like structures. The systemic administration of AdPPE3x-E1 reduced the lung metastases burden in a cotton rat model by 55%, compared with saline-treated rats, without significant evidence of toxicity. Quantitative PCR analysis showed that the viral copy number of AdPPE3x-E1 was increased 3-fold in the lung metastases but not in the liver, compared with a nonreplicating adenovector control.Conclusions: We have shown here for the first time an antimetastatic effect induced by an angiogenesis-transcriptionally targeted adenovirus following systemic administration. Because adenovirus replication is more efficient in humans than in cotton rats, we assume a significant effect for AdPPE3x-E1 treatment in fighting human solid tumors and metastases.
Polymorphisms in the FAS and FASL Genes and Survival of Early Stage Non–small Cell Lung Cancer
Authors: Park Jae Yong , Lee Won-Kee , Jung Duk-Ku , Choi Jin-Eun , Park Tae-In , Lee Eung-Bae , Cho Sukki , Park Ji-Young , Cha Sung-Ick , Kim Chang-Ho , Kam Sin , Jung Tae Hoon , Jheon Sanghoon 
Published: February 2009

Abstract
Purpose: This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non–small cell lung cancer (NSCLC) patients.
Experimental Design: Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G&gt;A (rs2234767) and -670A&gt;G (rs1800682) and FASL -844C&gt;T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.
Results: Patients with the GG and combined AG + GG genotypes of the FAS -670A&gt;G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio = 1.71, 95% confidence interval (95% CI) = 1.06-2.77, and P = 0.03; and adjusted hazard ratio = 1.48, 95% CI = 1.01-2.20, and P = 0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio = 1.87, 95% CI = 1.20-2.91, and P = 0.006; and adjusted hazard ratio = 1.31, 95% CI = 1.05-1.65, P = 0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG + GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P = 0.04).
Conclusion: The FAS -670A&gt;G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A&gt;G polymorphism can help identify patients at high risk for a poor disease outcome.
Treatment of Mammary Carcinomas in HER-2 Transgenic Mice through Combination of Genetic Vaccine and an Agonist of Toll-Like Receptor 9
Authors: Aurisicchio Luigi , Peruzzi Daniela , Conforti Antonella , Dharmapuri Sridhar , Biondo Antonella , Giampaoli Saverio , Fridman Arthur , Bagchi Ansu , Winkelmann Christopher T. , Gibson Raymond , Kandimalla Ekambar R. , Agrawal Sudhir , Ciliberto Gennaro , La Monica Nicola 
Published: February 2009

Abstract
Purpose: Oligodeoxynucleotides containing unmethylated CpG dinucleotides induce innate and adaptive immunity through Toll-like receptor 9 (TLR9). In the present study, we have examined the ability of a novel agonist of TLR9, called immunomodulatory oligonucleotide (IMO), to enhance effects of a HER-2/neu plasmid DNA electroporation/adenovirus (DNA-EP/Ad) vaccine.
Experimental Design: BALB/NeuT mice were treated with DNA-EP vaccine alone, IMO alone, or the combination of two agents starting at week 13, when all mice showed mammary neoplasia. Tumor growth and survival were documented. Antibody and CD8+ T-cell responses were determined. Peptide microarray analysis of sera was carried out to identify immunoreactive epitopes. Additionally, microCT and microPET imaging was carried out in an advanced-stage tumor model starting treatment at week 17 in BALB/NeuT mice.
Results: The combination of DNA-EP and IMO resulted in significant tumor regression or delay to tumor progression. 2-Deoxy-2-[18F]fluoro-d-glucose microPET and microCT imaging of mice showed reduced tumor size in the DNA-EP/IMO combination treatment group. Mice treated with the combination produced greater antibody titers with IgG2a isotype switch and antibody-dependent cellular cytotoxicity activity than did mice treated with DNA-EP vaccine. An immunogenic B-cell linear epitope, r70, within the HER-2 dimerization domain was identified through microarray analysis. Heterologous DNA-EP/Ad vaccination combined with IMO increased mice survival.
Conclusion: The combination of HER-2/neu genetic vaccine and novel agonist of TLR9 had potent antitumor activity associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities. These results support possible clinical trials of the combination of DNA-EP/Ad-based cancer vaccines and IMO.
Hypoxia Enhances Sphingosine Kinase 2 Activity and Provokes Sphingosine-1-Phosphate-Mediated Chemoresistance in A549 Lung Cancer Cells
Authors: Schnitzer Steffen E. , Weigert Andreas , Zhou Jie , Brüne Bernhard 
Published: February 2009

Abstract
Hypoxia and signaling via hypoxia-inducible factor-1 (HIF-1) is a key feature of solid tumors and is related to tumor progression as well as treatment failure. Although it is generally accepted that HIF-1 provokes tumor cell survival and induces chemoresistance under hypoxia, HIF-1-independent mechanisms operate as well. We present evidence that conditioned medium obtained from A549 cells, incubated for 24 h under hypoxia, protected naive A549 cells from etoposide-induced cell death. Lipid extracts generated from hypoxia-conditioned medium still rescued cells from apoptosis induced by etoposide. Specifically, the bioactive lipid sphingosine-1-phosphate (S1P) not only was essential for cell viability of A549 cells but also protected cells from apoptosis. We noticed an increase in sphingosine kinase 2 (SphK2) protein level and enzymatic activity under hypoxia, which correlated with the release of S1P into the medium. Knockdown of SphK2 using specific small interfering RNA relieved chemoresistance of A549 cells under hypoxia and conditioned medium obtained from SphK2 knockdown cells was only partially protective. Coincubations of conditioned medium with VPC23019, a S1P1/S1P3 antagonist, reduced protection of conditioned medium, with the further notion that p42/44 mitogen-activated protein kinase transmits autocrine or paracrine survival signaling downstream of S1P1/S1P3 receptors. Our data suggest that hypoxia activates SphK2 to promote the synthesis and release of S1P, which in turn binds to S1P1/S1P3 receptors, thus activating p42/44 mitogen-activated protein kinase to convey autocrine or paracrine protection of A549 cells. (Mol Cancer Res 2009;7(3):393–401)
Remote Sensing of Cloud-Top Pressure Using Moderately Resolved Measurements within the Oxygen A Band—A Sensitivity Study
Authors: Preusker Rene , Lindstrot Rasmus 
Published: February 2009

AbstractReflected solar radiation measured by the Medium Resolution Imaging Spectrometer (MERIS) on the Environmental Satellite (Envisat) is currently used within the European Space Agency’s ground segment for the retrieval of cloud-top pressure. The algorithm is based on the analysis of the gaseous absorption of solar radiation in the oxygen A band at 761 nm. The strength of absorption is directly related to the average photon pathlength, which is mainly determined by the cloud-top pressure. However, it additionally depends on surface and cloud properties, like cloud thickness and microphysics. The interpretation of the measurements is further complicated by the temperature dependence of the absorption line shapes and the sensitivity to the spectral properties of the spectrometer like spectral position and width. This paper is focused on results of sensitivity studies using the Matrix Operator Model (MOMO) radiative transfer model that examine the most important parameters affecting the measurements of MERIS or similar instruments. The cloud-top pressure retrieval scheme is briefly presented. An analysis of the information content and the degrees of freedom of measurements within the oxygen A band is included in this study.
A Method of Successive Corrections of the Control Subspace in the Reduced-Order Variational Data Assimilation*
Authors: Yaremchuk Max , Nechaev Dmitri , Panteleev Gleb 
Published: February 2009

Abstract
A version of the reduced control space four-dimensional variational method (R4DVAR) of data assimilation into numerical models is proposed. In contrast to the conventional 4DVAR schemes, the method does not require development of the tangent linear and adjoint codes for implementation. The proposed R4DVAR technique is based on minimization of the cost function in a sequence of low-dimensional subspaces of the control space. Performance of the method is demonstrated in a series of twin-data assimilation experiments into a nonlinear quasigeostrophic model utilized as a strong constraint. When the adjoint code is stable, R4DVAR’s convergence rate is comparable to that of the standard 4DVAR algorithm. In the presence of strong instabilities in the direct model, R4DVAR works better than 4DVAR whose performance is deteriorated because of the breakdown of the tangent linear approximation. Comparison of the 4DVAR and R4DVAR also shows that R4DVAR becomes advantageous when observations are sparse and noisy.
Ensemble Data Assimilation Applied to RAINEX Observations of Hurricane Katrina (2005)
Authors: Torn Ryan D. , Hakim Gregory J. 
Published: February 2009

Abstract
An ensemble Kalman filter (EnKF) based on the Weather Research and Forecasting model is applied to generate ensemble analyses and forecasts of Hurricane Katrina (2005) and the surrounding area every 6 h over the lifetime of the storm on a nested domain. Analyses are derived from assimilating conventional in situ observations, reconnaissance dropsondes, including data taken during the Hurricane Rainband and Intensity Exchange Experiment (RAINEX), and tropical cyclone position estimates. Observation assimilation at individual times consistently reduces errors in tropical cyclone position, but not necessarily in intensity; however, withholding observations leads to significantly larger errors in both quantities. Analysis increments for observations near the tropical cyclone are dominated by changes in vortex position, and these increments increase the asymmetric structure of the storm. Data denial experiments indicate that dropsondes deployed in the synoptic environment provide minimal benefit to the outer domain; however, dropsondes deployed within the tropical cyclone lead to significant reductions in position and intensity errors on the inner domain. Specifically, errors in the inner domain ensemble-mean 6-h forecasts of minimum pressure are 70% larger when dropsonde data is not assimilated. Precipitation fields are qualitatively similar to Tropical Rainfall Measuring Mission (TRMM) satellite estimates, although model values are double the values of the satellite estimate. Moreover, the spinup period and initial imbalance in EnKF-initialized WRF forecasts is less than starting the model from a GFS analysis. Ensemble-mean 48-h forecasts initialized with EnKF analyses have track and intensity errors that are 50% smaller than GFS and NHC official forecasts.
Evaluation of a Mesoscale Model with Different Surface Parameterizations and Vertical Resolutions for the Bay of Valencia
Authors: Ries Hinnerk , Schlünzen K. Heinke 
Published: February 2009

Abstract
Two different setups of the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) are used and the results of 71 forecasts are evaluated with a focus on the accuracy of meteorological surface data including wind, temperature, dewpoint temperature, and pressure. The forecasts, which cover the Valencia coastal region with a 3-km grid, are nested into two coarser grids of 9- and 27-km mesh size. The integration time is 18 h. The ability to correctly simulate the sea breeze plays a major role for this area. Different model setups are used: in the M1 simulations 34 atmospheric vertical sigma levels combined with a five-layer land surface model (5L LSM) are applied for the first half of the year 2006. In total, 52 atmospheric vertical sigma levels and the Noah LSM are used for the second half of 2006 (setup M2). The accuracy improves for all meteorological parameters except pressure with the M2 setup. However, negative biases of temperature, dewpoint temperature, and wind speed worsen. Detailed analysis of results for 4 days simulated with all combinations of vertical resolutions and LSMs shows that the increase of vertical resolution is responsible for the improved forecast performance. The Noah LSM generally improves temperature performance, but reduces the performance of all other parameters, especially for days with sea-breeze conditions. The Noah LSM performs better than the 5L LSM scheme only for a day driven by synoptic changes.
Costs and Benefits Associated With Diabetes Education A Review of the Literature
Authors: Boren Suzanne A. , Fitzner Karen A. , Panhalkar Pallavi S. , Specker James E. 
Published: February 2009

Purpose The purpose of this article was to review the published literature and evaluate the economic benefits and costs associated with diabetes education. Methods The Medline database (1991-2006) and Google were searched. Articles that addressed the economic and/or financial outcomes of a diabetes-related self-care or educational intervention were included. The study aim, population, design, intervention, financial and economic outcomes, results, and conclusions were extracted from eligible articles. Results Twenty-six papers were identified that addressed diabetes self-management training and education. Study designs included meta-analysis (1); randomized controlled trials (8); prospective, quasi-experimental, and pre-post studies (8); and retrospective database analyses (9). The studies conducted cost analyses (6), cost-effectiveness analyses (13), cost-utilization analyses (7), and number needed to treat analyses (2). More than half (18) of the 26 papers identified by the literature review reported findings that associated diabetes education (and disease management) with decreased cost, cost saving, cost-effectiveness, or positive return on investment. Four studies reported neutral results, 1 study found that costs increased, and 3 studies did not fit into these categories. Conclusions The findings indicate that the benefits associated with education on self-management and lifestyle modification for people with diabetes are positive and outweigh the costs associated with the intervention. More research is needed to validate that diabetes education provided by diabetes educators is cost-effective.
Health of Gullah Families in South Carolina With Type 2 Diabetes
Authors: Johnson-Spruill Ida , Hammond Pamela , Davis Bertha , McGee Zina , Louden Delroy 
Published: February 2009

Purpose The purpose of this study was to describe diabetes self-management practices and service utilization among Gullah families in South Carolina. Methods Data were obtained from 1276 persons with type 2 diabetes through interviews using the Family Health History Questionnaire. This was a primary analysis of a project conducted in conjunction with a parent study (Project SuGar) which focused on the molecular aspects of diabetes. Descriptive statistics were used for data analysis. Results Diabetes self-management behaviors were not consistent with recommendations from the American Diabetes Association. Over half (55.6%) reported exercising, but only 27.7% reported self-glucose monitoring. Service utilization was poor, less than half, (41.1%) reported referral to a diabetic class/diet, 32.8% reported making yearly visits to the ophthalmologist, 22.3% reported visiting the dentist, and only 12.8% reported visiting the podiatrist. Conclusions Although some self-management behaviors were identified, Gullah family members remain at risk for preventable diabetes complications. Education must reflect behaviors and beliefs valued by Gullah individuals. Culturally appropriate educational programs may increase use of health care services aimed at decreasing preventable complications of type 2 diabetes in the Gullah population.
In-vitro bioactivity of Venda medicinal plants used in the treatment of respiratory conditions
Authors: Pallant CA , Steenkamp V 
Published: February 2009

Infectious diseases, especially those affecting the respiratory tract, represent a critical problem to health. Crude methanol and water extracts of 10 Venda plants reported to be used ethnomedically in the treatment of respiratory conditions were assessed for their antimicrobial activity against standard strains and clinical isolates of Candida albicans, Haemophilis influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium smegmatis using the disc diffusion assay. Four of the 10 plants tested possessed antimicrobial activity, but no activity against K. pneumoniae was observed. Minimum inhibitory concentrations, as determined by the broth microdilution assay, showed three plants, Securidaca longepedunculata, Syzygium cordatum, and Tabernaemontana elegans, to possess MICs ≤ 1 mg/mL. Phytochemical screening, performed by separation on thin layer chromatography using a variety of mobile phases and visualization with spray reagents as well as UV light showed various classes of compounds in the active extracts. Some of these have been associated with antioxidant activity, as confirmed in this study. Moreover, these extracts showed toxicity in vitro to lymphocytes. Although three plant species with significant antimicrobial activity were identified, there is a need for further scientific evaluation regarding identification of the bioactive constituents, as well as their toxicity.
Influence of nitrogen fertilizers on yield and antifungal bioactivity of Tulbaghia violacea L.
Authors: van den Heever E , Allemann J , Pretorius JC 
Published: February 2009

Tulbaghia is known to have antifungal properties that can be used in the treatment of both human and plant pathogens and is used in traditional medicine in South Africa. Increasing demands for plant material makes it necessary to cultivate this species on a large scale. Unfortunately, cultivation can lead to a reduction in the biological activity of plants making them unsuitable for use. In light of the lack of knowledge regarding the agronomic requirements of this plant, the aim of this study was to determine the effect of several rates and two forms of nitrogenous fertilizer on the yield and biological activity of Tulbaghia violacea. Plants were cultivated in sand while the basic fertilization used was the same as that of garlic (20 kg P ha−1, 75 kg K ha−1), a plant from the same family, containing similar active ingredients. Nitrogen was applied once at the beginning of the trial at rates of 30, 60, 120, and 180 kg ha−1 in the form of either nitrate or ammonium. Vegetative growth was quantified in terms of number of leaves and leaf area as well as root and leaf dry mass, while harvested material was tested for antifungal activity. The results indicated that compared with the untreated control, increasing N-rates in both the nitrate and ammonium forms increased leaf number and leaf area as well as both root and leaf dry mass. However, at a rate above 60 kg ha−1, and especially at 180 kg ha−1, the nitrate form stimulated growth more markedly than the ammonium form, whereas antifungal activity decreased sharply and almost linearly as the application rate was increased. Although growth was not stimulated to the same extent by the ammonium form, it increased the in-vitro antifungal activity at different levels during different times of the growing season. From an ornamental perspective, nitrate is the preferred nitrogenous form but, from a bioactivity perspective, ammonium is recommended.