bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Phosphoinositide 3-Kinase/mTOR Dual Inhibitor, NVP-BGT226, Displays Potent Growth-Inhibitory Activity against Human Head and Neck Cancer Cells In Vitro and In Vivo
Authors: Chang Kwang-Yu , Tsai Shan-Yin , Wu Ching-Ming , Yen Chia-Jui , Chuang Bin-Fay , Chang Jang-Yang 
Published: October 2011

Abstract
Purpose: Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently accounts for the tumorigenesis in head and neck cancer. To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells.
Experimental Design: The in vitro antitumor effect of BGT226 was determined in various cancer cell lines. Animal models were also applied to examine drug potency. The inhibitory ability of BGT226 on the PI3K/AKT/mTOR signaling pathway was analyzed.
Results: The growth inhibition assay revealed that BGT226 was active against all tested cancer cell lines. Cross-resistance was not observed in the cisplatin-resistant cell line. The activation of the AKT/mTOR signal cascade was suppressed by BGT226 in a concentration- and time-dependent manner. Flow cytometric analysis revealed an accumulation of cells in the G0–G1 phase with concomitant loss in the S-phase. Results of the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) assay and the analysis of caspase 3/7 and PARP indicated that BGT226 induced cancer cell death through an apoptosis-independent pathway. BGT226 induced autophagy as indicated by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3-methyladenine, inhibited the BGT226-induced autophagy and led to the retrieval of colony survival. In a xenografted animal model, BGT226 significantly delayed tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase and the presence of autophagosome formation.
Conclusions: These data indicate that BGT226 is a potential drug in the treatment of head and neck cancer. Clin Cancer Res; 17(22); 7116–26. ©2011 AACR.
Genetic Variation in Inflammatory Pathways Is Related to Colorectal Cancer Survival
Authors: Coghill Anna E. , Newcomb Polly A. , Poole Elizabeth M. , Hutter Carolyn M. , Makar Karen W. , Duggan Dave , Potter John D. , Ulrich Cornelia M. 
Published: October 2011

Abstract
Purpose: Prognosis of patients with colorectal cancer (CRC) is associated with systemic inflammation, and anti-inflammatory drugs can reduce both CRC incidence and mortality. Genetic variation in proinflammatory pathways can affect an individual's CRC risk. However, few studies have investigated the prognostic importance of this genetic variation in CRC patients.
Experimental Design: We investigated the association between CRC survival and genetic variation in proinflammatory pathways among patients from the Puget Sound Surveillance Epidemiology and End Results registry. Single-nucleotide polymorphisms were genotyped in five genes (PTGS-1, PTGS-2, MRP4, NFκB, and IκBKβ). Vital status was ascertained through linkage to the National Death Index. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI). The false discovery rate method of Benjamini and Hochberg was applied to address multiple testing.
Results: Four PTGS-1 variants were associated with CRC survival. One, G&gt;A intron 9 (rs1213266), was associated with approximately 50% lower CRC mortality (HRAA/AG vs. GG = 0.48; 95% CI, 0.25–0.93). Three variants, including L237M, resulted in significantly elevated CRC mortality risk, with HRs ranging from approximately 1.5 to 2.0. Two variants in IκBKβ, including R526Q, were significantly associated with CRC survival. Correction for multiple testing indicated that variants in both PTGS-1 and IκBKβ are reproducibly associated with CRC survival.
Conclusion: Our findings suggest that genetic variation in proinflammatory pathways may be important for CRC prognosis. This investigation represents one of the first descriptions of the relationship between inherited polymorphisms and mortality in CRC patients and provides a starting point for further research. Clin Cancer Res; 17(22); 7139–47. ©2011 AACR.
The problem of accelerated atherosclerosis in systemic lupus erythematosus: Insights into a complex co-morbidity
Authors: Wade Nekeithia , Major Amy 
Published: October 2011

SummaryRheumatic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with antibodies to “self” antigens. Persons with autoimmune diseases, most notably SLE, are at increased risk for developing accelerated cardiovascular disease. The link between immune and inflammatory responses in the pathogenesis of cardiovascular disease has been firmly established; yet, despite our increasing knowledge, accelerated atherosclerosis continues to be a significant co-morbidity and cause of mortality in SLE. Recent animal models have been generated in order to identify mechanism(s) behind SLE-accelerated atherosclerosis. In addition, clinical studies have been designed to examine potential treatments options. This review will highlight data from recent studies of immunity in SLE and atherosclerosis and discuss the potential implications of these investigations.
Co-stimulatory molecules in and beyond co-stimulation – tipping the balance in atherosclerosis?
Authors: Gerdes Norbert , Zirlik Andreas 
Published: October 2011

SummaryA plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune- modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.
A novel splice variant of the stem cell marker LGR5/GPR49 is correlated with the risk of tumor-related death in soft-tissue sarcoma patients
Authors: Rot Swetlana , Taubert Helge , Bache Matthias , Greither Thomas , Würl Peter , Eckert Alexander W , Schubert Johannes , Vordermark Dirk , Kappler Matthias 
Published: October 2011

Abstract

Background
The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet.

Methods
Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant of LGR5/GPR49 lacking exon 5 (that we called GPR49Δ5) were quantified.

Results
A low mRNA expression level of GPR49Δ5, but not wild type LGR5/GPR49, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of GPR49Δ5 was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of GPR49Δ5 mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of GPR49Δ5 mRNA.

Conclusion
An attenuated mRNA level of the newly identified transcript variant GPR49Δ5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower GPR49Δ5 mRNA level is associated with a later age of tumor onset. A putative role of GPR49Δ5 expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested.
The curse of the prey: Sarcoptes mite molecular analysis reveals potential prey-to-predator parasitic infestation in wild animals from Masai Mara, Kenya
Authors: Gakuya Francis , Rossi Luca , Ombui Jackson , Maingi Ndichu , Muchemi Gerald , Ogara William , Soriguer Ramón C , Alasaad Samer 
Published: October 2011

Abstract

Background
Recently, there have been attempts to understand the molecular epidemiology of Sarcoptes scabiei, to evaluate the gene flow between isolates of S. scabiei from different hosts and geographic regions. However, to our knowledge, a molecular study has not been carried out to assess the molecular diversity and gene flow of Sarcoptes mite in a predator/prey ecosystem.

Results
Our study revealed an absence of gene flow between the two herbivore (Thomson's gazelle and wildebeest)- and between the two carnivore (lion and cheetah)-derived Sarcoptes populations from Masai Mara (Kenya), which is in discrepancy with the host-taxon law described for wild animals in Europe. Lion- and wildebeest-derived Sarcoptes mite populations were similar yet different from the Thomson's gazelle-derived Sarcoptes population. This could be attributed to Sarcoptes cross-infestation from wildebeest ("favourite prey") of the lion, but not from Thomson's gazelle. The cheetah-derived Sarcoptes population had different subpopulations: one is cheetah-private, one similar to the wildebeest- and lion-derived Sarcoptes populations, and another similar to the Thomson's gazelle-derived Sarcoptes mite population, where both wildebeest and Thomson's gazelle are "favourite preys" for the cheetah.

Conclusions
In a predator/prey ecosystem, like Masai Mara in Kenya, it seems that Sarcoptes infestation in wild animals is prey-to-predator-wise, depending on the predator's "favourite prey". More studies on the lion and cheetah diet and behaviour could be of great help to clarify the addressed hypotheses. This study could have further ramification in the epidemiological studies and the monitoring protocols of the neglected Sarcoptes mite in predator/prey ecosystems.
Testing different methods for estimating uncertainties on Rietveld refined parameters using SrRietveld
Authors: Tian Peng , Billinge Simon 
Published: October 2011

Abstract
The advent of fast computing allows more computationally expensive, though possibly more accurate, approaches for estimating uncertainties on Rietveld refined parameters. Here we compare three such methods, using two different refinement programs, FullProf and GSAS. This is facilitated by the use of a new Rietveld refinement package, SrRietveld, that provides Python wrappers for FullProf and GSAS. The refined values on the parameters from two different refinement engines match each other very well. The uncertainty estimates determined using the different methods are also consistent, though FullProf and GSAS estimate the parameter uncertainties slightly differently from each other, which is discussed. More importantly, we find that the refined results are very sensitive to the statistical weights used in the least squares equation. Different weights, for example from uncertain or incorrectly propagated random errors on the data, lead to significantly different refined values. This means that uncertainty estimates on refined parameters should be increased when the random errors on the data are not well known, as for example in many cases where area detectors are used, and care should be taken to propagate errors correctly in any data preprocessing such as normalization by a smoothed spectrum. The computationally expensive bootstrap error estimation methods are facilitated by the use of SrRietveld, but are not required in most cases though may be useful in some cases, for example if the random errors on the data are not well known.
Characterization of Rhodamine 6G Release in Electrospray Ionization by Means of Spatially Resolved Fluorescence Spectroscopy
Authors: Riebe Daniel , Zühlke Martin , Zenichowski Karl , Beitz Toralf , Dosche Carsten , Löhmannsröben Hans-Gerd 
Published: October 2011

Abstract
In the present work, the density distribution of rhodamine 6G ions (R6G) in the gas phase and the droplets of an electrospray plume was studied by spatial and spectral imaging. The intention is to contribute to the fundamental understanding of the release mechanism of gaseous R6G in the electrospray ionization (ESI) process. Furthermore, the influence of ESI-parameters on the release efficiency of R6G, e.g. solvent flow, R6G and salt concentration were examined via direct fluorescence imaging of R6G. A solvent-shift of the fluorescence maximum, λ
max = 555 nm in methanolic solution and λ
max = 505 nm in gas phase, allows the discrimination between solvated and gaseous R6G. Two experimental setups were used for our measurements. In the first experiment, the R6G fluorescence and the light scattered from the spray plume were imaged in two spatial dimensions using a tunable wavelength fil ter. The second experiment was designed for obtaining 1-dimensional spatially resolved emission spectra of the spray. Here, the intensity distribution of solvated and gaseous R6G as well as scattered light (λ=355 nm) were measured simultaneously.
The results show the distribution of gaseous R6G in the plane, orthogonal to the ESI capillary, decreasing slightly towards the spray center and showing maxima at the cone margins. The distribution of gaseous R6G confirms the preferred release of gaseous ions from nano-droplets, indicating the ion evaporation model (IEM) to be the dominating release mechanism. Up to now, only a few fluorescence spectra of ionic compounds in the gas phase were published because the measurement of emission spectra of mass-selected ions in an ion trap is experimentally challenging. The fluorescence spectrum of gaseous lucigenin at atmospheric pressure is reported for the first time. This spectrum of lucigenin in the gas phase exhibits a blue shift of about Δλ=10 nm in comparison to the corresponding spectrum in methanol.
Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors
Authors: Chisalita Simona I , Dahlström Ulf , Arnqvist Hans J , Alehagen Urban 
Published: October 2011

ObjectiveThere are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors.Design and methodsA total of 851 persons aged 66–81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years.Results and conclusionPatients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) <40% compared with EF ≥40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P<0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (P=0.03). This was significant after adjustment for well-known CV risk factors and ACE inhibitors (P=0.03).ConclusionsOur results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality.
Genetic Analysis of Populations Derived from Matings of Southern and Northern Soybean Cultivars
Authors: Feng L. , Burton J.W. , Carter T.E. , Miranda L.M. , St. Martin S.K. , Brownie C. 
Published: October 2011

ABSTRACTGenetic diversity is one of the important considerations in selecting parents for applied cultivar development in soybean [Glycine max (L.) Merr.]. Recent studies have shown that southern and northern U.S. soybean cultivars belong to two very distinct gene pools based on pedigree and molecular marker analysis. A study was conducted to evaluate the potential of matings between southern and northern cultivars for applied soybean breeding. Nine populations were derived from matings of two southern soybean cultivars, Johnston and Stonewall, with three ancestral, A.K. (Harrow), Lincoln, and Mandarin, and three improved, Flyer, Sibley, and Zane, northern cultivars. Field trials showed statistically significant differences among and within crosses for mean yield, maturity, height, seed quality, seed weight, protein, oil, and fatty acid composition. There were significant differences in means and genetic variances among populations derived from male (northern) cultivars for mean yield and all other traits recorded. Results suggested that improved northern cultivars would be useful parents for practical breeding programs in the south. Populations derived from Flyer produced the highest mean yields. A significant correlation (r = –0.82) between coefficient of parentage (CP) value and genetic variance estimate for cross yield may indicate that CP is a useful measurement in predicting genetic variation among matings of inbred soybean cultivars.
The Positional Effects of Auxin and Cytokinin on the Regulation of Rice Tiller Bud Growth
Authors: Liu Yang , Ding Yanfeng , Gu Dandan , Li Ganghua , Wang Qiangsheng , Wang Shaohua 
Published: October 2011

ABSTRACTAuxin and cytokinin (CTK) play important roles in the regulation of rice (Oryza sativa L.) tiller bud growth. Auxin inhibits bud growth and CTK promotes growth; however, little is known about the positional effects of these hormones in the regulation of rice tiller bud growth. In the present study, indole‐3‐acetic acid (IAA) and 6‐benzylaminopurine (6‐BA) (a synthetic CTK) were applied to different leaves and roots at the tillering and heading stages of rice development, and the growth of rice tiller buds on the unelongated and elongated internodes was measured. Additionally, hormonal variations of the plants were examined and recorded. The objectives of the present study were to investigate the positional effects of auxin and CTK on the regulation of rice tiller bud growth. The results indicate that IAA has a notable positional effect on the regulation of rice tiller bud growth, and the positional effect of IAA was closely related to its polar transport. An increase in leaf IAA levels inhibited the growth of tiller buds located at unelongated nodes; however, growth of tiller buds at elongated nodes was inhibited only when IAA levels were increased in the upper‐stem leaves or the leaves at which the tiller bud was located. Contrary to IAA, 6‐BA had no positional effect on rice tiller bud growth. Application of 6‐BA to different leaves and roots significantly promoted the growth of rice tiller buds at both unelongated and elongated nodes.
Quantitative Trait Loci Analysis for the Effect of Rht‐B1 Dwarfing Gene on Coleoptile Length and Seedling Root Length and Number of Bread Wheat
Authors: Li P. , Chen J. , Wu P. , Zhang J. , Chu C. , See D. , Brown‐Guedira G. , Zemetra R. , Souza E. 
Published: October 2011

ABSTRACTIt has been documented that the dwarfing genes, Rht‐B1b and Rht‐D1b, can reduce wheat (Triticum aestivum L.) coleoptile length (CL), but their effects on number of roots (RN) and root length (RL) have not been determined. Our objectives were to identify quantitative trait loci (QTL) controlling CL, RN, and RL and to determine if any of the QTL correspond to wheat dwarfing genes. A population consisting of 159 recombinant inbred lines (RILs) was derived from the cross of Rio Blanco (Rht‐B1b, Rht‐D1a), a semidwarf cultivar with short CL, and IDO444 (Rht‐B1a, Rht‐D1a), a tall germplasm with long CL. The CL, RN, longest root length (LRL), and total root length (TRL) were evaluated at two temperature regimes (18 and 22°C). A major QTL mapped to the Rht‐B1 locus on chromosome 4B explained 64% of the phenotypic variation for CL, 9% for LRL, 26% for TRL, and 14% for plant height. The CL of the semidwarf RILs was significantly less than that of the tall lines while the reverse results were observed for LRL and TRL. Our results indicated that the Rht‐B1 gene had the pleiotropic effect of decreasing CL while increasing LRL and TRL. None of the six QTL for RN were mapped to the regions containing the Rht‐B1 locus although semidwarf RILs had more roots than the tall lines. This study suggested that selection of the Rht‐B1b allele tended to increase root biomass, perhaps ameliorating its negative effect of reduced CL.
Transgenic Rice Expressing a Fusion Protein of Cry1Ab and Cry9Aa Confers Resistance to a Broad Spectrum of Lepidopteran Pests
Authors: Gao Jianhua , Zhang Yu'e , Zhao Qichao , Lin Chaoyang , Xu Xiaoli , Shen Zhicheng 
Published: October 2011

ABSTRACTThe truncated active Bacillus thuringiensis endotoxin genes, cry1Ab and cry9Aa, were fused to create a fusion gene, cry1Ab–cry9Aa, encoding a protein of about 146 kDa with Cry1Ab at the N terminus and Cry9Aa at the C terminus. The fusion protein expressed in Escherichia coli is highly active against some major lepidopteran pests—oriental armyworm [Mythimna separata (Walker)], Asian corn borer [Ostrinia furnacalis (Guenée)], cotton bollworm [Helicoverpa armigera (Hübner)], and tobacco cutworm [Spodoptera litura (Fabricius)]. This fusion gene under the control of the corn (Zea mays L.) polyubiquitin‐1 promoter was transformed into rice (Oryza sativa L.) via Agribacterium‐mediated transformation. Western blot analysis suggested that the transgenic lines, C19‐2 and C19‐25, were two high expressers among the 35 transgenic lines obtained. Southern blot analysis revealed that the line C19‐2 contains a single copy of the T‐DNA, while the C19‐25 has three copies. Insecticidal activity assays demonstrated that most of the transgenic rice lines expressing this fusion protein are highly resistant to rice stem borer [Chilo suppressalis (Walker)] and rice leaf folder [Cnaphalocrocis medinalis (Guenée)]. This study suggested that this fusion gene could be useful for engineering transgenic crops for the control of lepidopteran pests.
The Value of "Vehicle to Grid" Integration into Warehouse Logistics Management - Case of Slovenian Retailer
Authors: Knez Matjaž , Bajor Peter 
Published: October 2011

The Value of "Vehicle to Grid" Integration into Warehouse Logistics Management - Case of Slovenian Retailer
Wide-scale application photovoltaic energy sources for electricity production purposes is quite a challenge in Slovenia. The nature of sun is unpredictable, and the Slovenian National Grid has no significant storage opportunities today - if the V2G (vehicle-to-grid) solutions could be competitive in the near future we could prepare for the special circumstances: the batteries of electrically driven forklifts could provide attractive storage functions for renewable electricity storage. The following paper presents an overview of some "environmental background approaches" to show the complexity of this innovative system and to show the value of V2G technology and its application in warehouse logistics.