bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strong Convergence of an Implicit Algorithm in CAT(0) Spaces
Authors: Fukhar-ud-din Hafiz , Domlo AbdulAziz , Khan AbdulRahim 
Published: January 2011

AbstractWe establish strong convergence of an implicit algorithm to a common fixed point of a finite family of generalized asymptotically quasi-nonexpansive maps in CAT"Equation missing" spaces. Our work improves and extends several recent results from the current literature.
Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib
Authors: Janjigian Yelena Y. , Azzoli Christopher G. , Krug Lee M. , Pereira Leanne K. , Rizvi Naiyer A. , Pietanza M Catherine , Kris Mark G. , Ginsberg Michelle S. , Pao William , Miller Vincent A. , Riely Gregory J. 
Published: January 2011

AbstractPurpose: In patients with epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma, treatment with erlotinib or gefitinib is associated with a 75% radiographic response rate and progression-free survival of approximately 12 months. The most common mechanism of acquired resistance to erlotinib is development of a secondary mutation in EGFR, suggesting that these tumors continue to depend on EGFR signaling. We hypothesized that combined EGFR blockade would overcome acquired resistance to erlotinib in patients with lung adenocarcinoma. To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial.Experimental Design: Patients with lung adenocarcinoma and clinically defined acquired resistance to erlotinib were treated with erlotinib 100 mg daily, along with cetuximab every 2 weeks in three escalating dose cohorts (250 mg/m2, 375 mg/m2, and 500 mg/m2). The recommended phase II dose was then evaluated in a two-stage trial, with a primary end point of objective response rate.Results: A total of 19 patients were enrolled. The most common toxicities for the combination of cetuximab and erlotinib were rash, fatigue, and hypomagnesemia. The recommended phase II dose identified was cetuximab 500 mg/m2 every 2 weeks and erlotinib 100 mg daily. At this dose and schedule, no radiographic responses were seen (0 of 13, 0%, 95% CI, 0–25).Conclusions: Combined EGFR inhibition, with cetuximab 500 mg/m2 every 2 weeks and erlotinib 100 mg daily, had no significant activity in patients with acquired resistance to erlotinib. Clin Cancer Res; 17(8); 2521–7. ©2011 AACR.
Nouveau-ROUGE: A Novelty Metric for Update Summarization
Authors: Conroy John M. , Schlesinger Judith D. , O'Leary Dianne P. 
Published: January 2011

An update summary should provide a fluent summarization of new information on a time-evolving topic, assuming that the reader has already reviewed older documents or summaries. In 2007 and 2008, an annual summarization evaluation included an update summarization task. Several participating systems produced update summaries indistinguishable from human-generated summaries when measured using ROUGE. However, no machine system performed near human-level performance in manual evaluations such as pyramid and overall responsiveness scoring. We present a metric called Nouveau-ROUGE that improves correlation with manual evaluation metrics and can be used to predict both the pyramid score and overall responsiveness for update summaries. Nouveau-ROUGE can serve as a less expensive surrogate for manual evaluations when comparing existing systems and when developing new ones.
Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities
Authors: Collett Johnny , Dawes Helen , Meaney Andy , Sackley Cath , Barker Karen , Wade Derick , Izardi Hooshang , Bateman James , Duda Joan , Buckingham Elizabeth 
Published: January 2011

Background: The most effective exercise dose has yet to be established for multiple sclerosis (MS). Objective: The aim of this study was to investigate the effect of different exercise intensities in people with MS. Methods: We completed a randomized comparator study of three cycling exercise intensities, with blinded assessment, was carried out in Oxford. Sixty-one adults with MS who fulfilled inclusion criteria were randomized at entry into the study, using a computer-generated list held by an exercise professional, into either: continuous (at 45% peak power, n = 20), intermittent (30 sec on, 30 sec off at 90% peak power, n = 21) or combined (10 min intermittent at 90% peak power then 10 min continuous at 45% peak power, n = 20) exercise for 20 min twice a week for 12 weeks in a leisure facility. Groups were assessed at: baseline, halfway (6 weeks), end intervention (12 weeks) and follow-up (24 weeks). Primary outcome measure was 2 min walk. Results: Fifty-five participants were included in the analysis ( n = continuous 20, intermittent 18, combined 17). No differences were found between groups. After 6 weeks, considering all participants, 2 min walk distance increased by 6.96 ± 2.56 m (95% CI: 1.81 to 12.10, effect size (es): 0.25, p < 0.01). The continuous group increased by 4.71 ± 4.24 m (95% CI: −3.80 to 13.22, es : 0.06), intermittent by 12.94 ± 4.71 m (95% CI: 3.97 to 21.92, es: 0.28) and combined by 3.22 ± 4.60 m (95% CI: −6.01 to 12.46, es: 0.04) . Two minute walk did not significantly change between further assessments. Between 6 and 12 weeks there was a drop in attendance that seemed to be associated with the intermittent and combined groups; these groups also had a greater number of adverse events (leg pain during cycling most common) and dropouts ( n = continuous 1, intermittent 5, combined 10). Considering all participants, 6 weeks of cycling exercise produced benefits in mobility that were maintained with further sessions. Conclusion: While no differences were found between groups, greater benefit may be associated with higher-intensity exercise, but this may be less well tolerated.CONSORT - trial registration number (ISRCTN89009719)
An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations
Authors: Almeida Marcio AA , Oliveira Paulo SL , Pereira Tiago V , Krieger José E , Pereira Alexandre C 
Published: January 2011

Abstract

Background
Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers.

Results
In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10 -5 for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers.

Conclusions
Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies.
False negative rates in Drosophila cell-based RNAi screens: a case study
Authors: Booker Matthew , Samsonova Anastasia A , Kwon Young , Flockhart Ian , Mohr Stephanie E , Perrimon Norbert 
Published: January 2011

Abstract

Background
High-throughput screening using RNAi is a powerful gene discovery method but is often complicated by false positive and false negative results. Whereas false positive results associated with RNAi reagents has been a matter of extensive study, the issue of false negatives has received less attention.

Results
We performed a meta-analysis of several genome-wide, cell-based Drosophila RNAi screens, together with a more focused RNAi screen, and conclude that the rate of false negative results is at least 8%. Further, we demonstrate how knowledge of the cell transcriptome can be used to resolve ambiguous results and how the number of false negative results can be reduced by using multiple, independently-tested RNAi reagents per gene.

Conclusions
RNAi reagents that target the same gene do not always yield consistent results due to false positives and weak or ineffective reagents. False positive results can be partially minimized by filtering with transcriptome data. RNAi libraries with multiple reagents per gene also reduce false positive and false negative outcomes when inconsistent results are disambiguated carefully.
Development of genic-SSR markers by deep transcriptome sequencing in pigeonpea [Cajanus cajan (L.) Millspaugh]
Authors: Dutta Sutapa , Kumawat Giriraj , Singh Bikram P , Gupta Deepak K , Singh Sangeeta , Dogra Vivek , Gaikwad Kishor , Sharma Tilak R , Raje Ranjeet S , Bandhopadhya Tapas K , Datta Subhojit , Singh Mahendra N , Bashasab Fakrudin , Kulwal Pawan , Wanjari KB , K Varshney Rajeev , Cook Douglas R , Singh Nagendra K 
Published: January 2011

Abstract

Background
Pigeonpea [Cajanus cajan (L.) Millspaugh], one of the most important food legumes of semi-arid tropical and subtropical regions, has limited genomic resources, particularly expressed sequence based (genic) markers. We report a comprehensive set of validated genic simple sequence repeat (SSR) markers using deep transcriptome sequencing, and its application in genetic diversity analysis and mapping.

Results
In this study, 43,324 transcriptome shotgun assembly unigene contigs were assembled from 1.696 million 454 GS-FLX sequence reads of separate pooled cDNA libraries prepared from leaf, root, stem and immature seed of two pigeonpea varieties, Asha and UPAS 120. A total of 3,771 genic-SSR loci, excluding homopolymeric and compound repeats, were identified; of which 2,877 PCR primer pairs were designed for marker development. Dinucleotide was the most common repeat motif with a frequency of 60.41%, followed by tri- (34.52%), hexa- (2.62%), tetra- (1.67%) and pentanucleotide (0.76%) repeat motifs. Primers were synthesized and tested for 772 of these loci with repeat lengths of ≥18 bp. Of these, 550 markers were validated for consistent amplification in eight diverse pigeonpea varieties; 71 were found to be polymorphic on agarose gel electrophoresis. Genetic diversity analysis was done on 22 pigeonpea varieties and eight wild species using 20 highly polymorphic genic-SSR markers. The number of alleles at these loci ranged from 4-10 and the polymorphism information content values ranged from 0.46 to 0.72. Neighbor-joining dendrogram showed distinct separation of the different groups of pigeonpea cultivars and wild species. Deep transcriptome sequencing of the two parental lines helped in silico identification of polymorphic genic-SSR loci to facilitate the rapid development of an intra-species reference genetic map, a subset of which was validated for expected allelic segregation in the reference mapping population.

Conclusion
We developed 550 validated genic-SSR markers in pigeonpea using deep transcriptome sequencing. From these, 20 highly polymorphic markers were used to evaluate the genetic relationship among species of the genus Cajanus. A comprehensive set of genic-SSR markers was developed as an important genomic resource for diversity analysis and genetic mapping in pigeonpea.
Enhanced genetic maps from family-based disease studies: population-specific comparisons
Authors: He Chunsheng , Weeks Daniel E , Buyske Steven , Abecasis Goncalo R , Stewart William C , Matise Tara C ,   The Enhanced Map Consortium
Published: January 2011

AbstractBackgroundAccurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps.ResultsWe collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths.ConclusionsOur new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.
Breast cancer and human papillomavirus infection: No evidence of HPV etiology of breast cancer in Indian women
Authors: Hedau Suresh , Kumar Umesh , Hussain Showket , Shukla Shirish , Pande Shailja , Jain Neeraj , Tyagi Abhishek , Deshpande Trivikram , Bhat Dilafroze , Mir Mohammad Muzaffar , Chakraborty Sekhar , Singh Y Mohan , Kumar Rakesh , Somasundaram Kumaravel , Bharti Alok C , Das Bhudev C 
Published: January 2011

Abstract

Background
Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions.

Methods
The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested.

Results
All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences.

Conclusions
Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.
Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells
Authors: Tatsukawa Hideki , Sano Tetsuro , Fukaya Yayoi , Ishibashi Naoto , Watanabe Makiko , Okuno Masataka , Moriwaki Hisataka , Kojima Soichi 
Published: January 2011

Abstract

Background
Hepatocellular carcinoma has a high mortality rate due to its rate of recurrence. Acyclic retinoid prevents recurrence of hepatocellular carcinoma in patients after surgical removal of their primary tumors by inducing apoptosis in hepatocellular carcinoma cells, although the molecular mechanisms of action are not understood.

Methods
Human hepatocellular carcinoma cells in culture, as well as nude mice transplanted with hepatocellular carcinoma cells and rats given with N-diethylnitrosamine were treated with acyclic retinoid. Changes in activated caspase 3 and transglutaminase 2 (TG2) levels, Sp1 cross-linking and its activities, expression of epidermal growth factor receptor, and apoptotic levels were measured.

Results
Acyclic retinoid simultaneously stimulated the activation of caspase 3, and the expression, nuclear localization and crosslinking activity of TG2, resulting in crosslinking and inactivation of the transcription factor, Sp1, thereby reducing expression of epidermal growth factor receptor and cell death in three hepatocellular carcinoma cell lines. These effects were partially restored by a caspase inhibitor, transfection of antisense TG2, restoration of functional Sp1, or an excess of epidermal growth factor. Nuclear expression of TG2 and crosslinked Sp1, as also activated caspase 3 were found in both hepatocellular carcinoma cells transplanted into nude mice and cancerous regions within the liver in N-diethylnitrosamine-induced hepatocarcinogenesis model in rats, following treatment of animals with acyclic retinoid.

Conclusions
Treatment with acyclic retinoid produces a dual activation of caspase 3 and TG2 induced apoptosis of hepatocellular carcinoma cells via modification and inactivation of Sp1, resulting in reduced expression of epidermal growth factor receptor.
Analysis of the proteome of human airway epithelial secretions
Authors: Ali Mehboob , Lillehoj Erik P , Park Yongsung , Kyo Yoshiyuki , Kim K Chul 
Published: January 2011

Abstract

Background
Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus.

Results
Fifty-five proteins were identified in the high molecular weight fraction of apical secretions collected from in vitro cultures of well-differentiated primary human airway epithelial cells and isolated under physiological conditions. Among these were MUC1, MUC4, MUC5B, and MUC16 mucins. By proteomic analysis, the nonmucin proteins could be classified as inflammatory, anti-inflammatory, anti-oxidative, and/or anti-microbial.

Conclusions
Because the majority of the nonmucin proteins possess molecular weights less than that selected for analysis, it is theoretically possible that they may associate with the high molecular weight and negatively charged mucins to form a highly ordered structural organization that is likely to be important for maintaining the proper defensive function of airway mucus.
Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids
Authors: Kamili Alvin , Wat Elaine , Chung Rosanna WS , Tandy Sally , Weir Jacquelyn M , Meikle Peter J , Cohn Jeffrey S 
Published: January 2011

Abstract

Background
Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake.

Methods
Mice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated: a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS.

Results
Both PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, P < 0.05). Hepatic accumulation of intragastrically-administered [14C]cholesterol was significantly less (-30% to -60%, P < 0.05) and fecal excretion of [14C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, P < 0.05). Liver cholesterol and triglyceride levels were positively correlated with hepatic accumulation of intragastrically-administered [14C]cholesterol (P < 0.001) and negatively correlated with fecal excretion of [14C]cholesterol (P < 0.05). Increased PL and ceramide levels in the diet of mice supplemented with milk PL were associated with significantly higher levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and ceramide, specifically, phosphatidylcholine (-21%, P < 0.05) and monohexosylceramide (-33%, P < 0.01).

Conclusion
These results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.