Big Data Challenges in Bioinformatics – The Collision of Technology and Biology

With advances in technology comes the ability of biologists to generate large amounts of data quickly and cost-effectively. This data explosion presents unique challenges not only in data storage, management, transfer, and analysis, but in arming biologists with the tools and knowledge to effectively use technology and interpret data

Relationship Between Student Academic Achievement and Gender of Campus Administrator

Studies of the effectiveness of women’s leadership have been recommended by researchers for over three decades (e.g. Eckman, 2004; Edson, 1988; Schmuck, 1981; Shakeshaft, 1989). Burke & Nelson (2002) and Smulyan (2000) have suggested that a woman’s leadership experience is fundamentally influenced by gender. As greater numbers of women fill educational administration positions previously held by men (Addi-Raccah, 2006; Rusch & Marshall, 2006), opportunities to study leadership differences and effectiveness of men and women in meeting unique demands of their campuses can be measured. Although issues related to women leaders in superintendent positions have been explored (Tallerico, 1999; Brunner, 1999; Blount, 1998; Grogan, 1996), few studies have investigated women’s leadership at the campus level (Goldberg, 1991; Ortiz 1982; Shakeshaft, 1989; Schneider, 1986). Furthermore, identification of the complex leadership attributes of women might clarify the dynamics of their advancement into campus administration (Burke &Nelson, 2002)

Activation and Molecular Targets of Peroxisome Proliferator-Activated Receptor-γ Ligands in Lung Cancer

Lung cancer is the leading cause of cancer death, and five-year survival remains poor, raising the urgency for new treatment strategies. Activation of PPARγ represents a potential target for both the treatment and prevention of lung cancer. Numerous studies have examined the effect of thiazolidinediones such as rosiglitazone and pioglitazone on lung cancer cells in vitro and in xenograft models. These studies indicate that activation of PPARγ inhibits cancer cell proliferation as well as invasiveness and metastasis. While activation of PPARγ can occur by direct binding of pharmacological ligands to the molecule, emerging data indicate that PPARγ activation can occur through engagement of other signal transduction pathways, including Wnt signaling and prostaglandin production. Data, both from preclinical models and retrospective clinical studies, indicate that activation of PPARγ may represent an attractive chemopreventive strategy. This article reviews the existing biological and mechanistic experiments focusing on the role of PPARγ in lung cancer, focusing specifically on nonsmall cell lung cancer

Rural Principal Leadership Skill Proficiency And Student Achievement

Warren and Peel (2005) found that rural schools can effectively develop focused leadership support and training. However, as indicated by Arnold, et al. (2004), the knowledge and skills most critical to effective rural administration have yet to be identified. Targeting specific leadership skills related to student achievement might focus university principal preparation programs and public school district staff development programs on producing more effective rural leadership. Ultimately, this emphasis may improve student achievement and school performance in rural schools. Because of the importance of developing highly skilled rural school leaders, this study will endeavor to identify the leadership skills of practicing rural administrators and determine whether these skills were related to campus student achievement

Welfare Research Perspectives: Past, Present, and Future, 2000 Edition

This is the second in a series of three working papers designed to examine what has been learned since the enactment of the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996

Analyse des therapeutischen Potentials von Cx43-exprimierenden Skelettmuskelzellen zur Prävention spontaner Arrhythmien nach Herzinfarkt

Als Folge der myokardialen Ischämie durch einen Herzinfarkt gehen Kardiomyozyten zugrunde und neben einer Herzinsuffizienz können lebensbedrohliche Herzrhythmusstörungen wie Kammertachykardien und Kammerflimmern auftreten. Um das durch den Infarkt zerstörte Gewebe zu ersetzen, sind in der Vergangenheit Zelltransplantationen durchgeführt worden. Wenig untersucht war bislang jedoch, ob die transplantierten Zellen auch die Gefahr von Rhythmusstörungen senken können. Durch elektrophysiologische Katheter-Untersuchungen an Mäusen konnte am Institut für Physiologie I (Roell et al., 2007) gezeigt werden, dass die Zelltherapie mit elektrisch koppelnden Zellen die Vulnerabilität gegenüber induzierten Herzrhythmusstörungen deutlich senkt. Dabei erwiesen sich Skelettmuskelzellen aus transgenen Mäusen, die das „Kopplungs-Protein“ Cx43 überexprimieren, ähnlich wirkungsvoll wie embryonale Kardiomyozyten. In der vorliegenden Arbeit wurden in einem weiterentwickelten Ansatz, mit dem Ziel der späteren klinischen Anwendung, allogene Skelettmuskelzellen (sowohl embryonale als auch adulte) aus genetisch unveränderten Tieren für Transplantationsexperimente verwendet, in die Cx43 mittels lentiviraler Transduktion in vitro eingebracht wurde. Die Funktionalität des Cx43-Konstruktes wurde mittels immunhistologischen Methoden untersucht und die Kopplung der Zellen in vitro durch Farbstofftransferexperimente nachgewiesen. Dazu wurde die neue Methode der lokalen Einzelzellelektroporation entwickelt, die das gezielte Einbringen von Substanzen in einzelne Zellen ermöglicht. Durch die Verwendung von Farbstoffen mit unterschiedlichen Molekulargewichten konnte eine interzelluläre Kopplung ausschließlich über Gap Junctions nachgewiesen und zytoplasmatische Brücken ausgeschlossen werden. Die Transplantation der mit Cx43 transduzierten Skelettmuskelzellen in den Herzinfarkt von Mäusen senkte die elektrische Vulnerabilität des Herzens in der elektrophysiologischen Untersuchung in vivo auf das Niveau von gesunden Tieren (invasive Experimente durchgeführt von A. Klein). Neben der Auswirkung der Zellersatztherapie auf induzierte Herzrhythmusstörungen wurden insbesondere das Auftreten von spontanen, arrhythmischen Episoden in vivo mit zwei verschiedenen EKG-Ableitungsmethoden untersucht: eine Extremitätenableitung und eine Langzeit EKG-Messung unter Verwendung eines telemetrischen Systems. Zur semiautomatischen EKG-Analyse wurde eine Software entwickelt, die die Quantifizierung von spontanen Arrhythmien erlaubt. Auch mit dieser Methode waren Hinweise auf einen antiarrhythmogenen Effekt der Zelltherapie des Herzinfarktes mit Cx43-positiven Skelettmuskelzellen erkennbar. Die autologe, zelluläre Ersatztherapie nach Herzinfarkt stellt, bei Verwendung von elektrisch koppelnden Zellen, einen vielversprechenden Ansatz für eine zukünftige klinische Anwendung am Menschen dar. Die Verwendung von genetisch unveränderten Zellen, die in vitro lentiviral transduziert und anschließend erst für Implantationen verwendet werden, ist dabei ethisch unbedenklich sowie vermutlich nebenwirkungsarm

Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples

Available statistical preprocessing or quality control analysis tools for gene expression microarray datasets are known to greatly affect downstream data analysis, especially when degraded samples, unique tissue samples, or novel expression assays are used. It is therefore important to assess the validity and impact of the assumptions built in to preprocessing schemes for a dataset. We developed and assessed a data preprocessing strategy for use with the Illumina DASL-based gene expression assay with partially degraded postmortem prefrontal cortex samples. The samples were obtained from individuals with autism as part of an investigation of the pathogenic factors contributing to autism. Using statistical analysis methods and metrics such as those associated with multivariate distance matrix regression and mean inter-array correlation, we developed a DASL-based assay gene expression preprocessing pipeline to accommodate and detect problems with microarray-based gene expression values obtained with degraded brain samples. Key steps in the pipeline included outlier exclusion, data transformation and normalization, and batch effect and covariate corrections. Our goal was to produce a clean dataset for subsequent downstream differential expression analysis. We ultimately settled on available transformation and normalization algorithms in the R/Bioconductor package lumi based on an assessment of their use in various combinations. A log2-transformed, quantile-normalized, and batch and seizure-corrected procedure was likely the most appropriate for our data. We empirically tested different components of our proposed preprocessing strategy and believe that our results suggest that a preprocessing strategy that effectively identifies outliers, normalizes the data, and corrects for batch effects can be applied to all studies, even those pursued with degraded samples

The effects of globin on microarray-based gene expression analysis of mouse blood

Peer reviewe

Gene expression profiling of human whole blood samples with the Illumina WG-DASL assay

<p>Abstract</p> <p>Background</p> <p>Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole genome DASL assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We assessed the utility of the whole genome DASL assay in an analysis of peripheral whole blood gene expression profiles.</p> <p>Results</p> <p>We find that gene expression detection is significantly increased with the use of whole genome DASL compared to the standard IVT-based direct hybridization. Additionally, globin-probe negative whole genome DASL did not exhibit significant improvements over globin-probe positive whole genome DASL. Globin reduction further increases the detection sensitivity and reliability of both whole genome DASL and IVT-based direct hybridization with little effect on raw intensity correlations. Raw intensity correlations between total RNA and globin reduced RNA were 0.955 for IVT-based direct hybridization and 0.979 for whole genome DASL.</p> <p>Conclusions</p> <p>Overall, the detection sensitivity of the whole genome DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies.</p