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Search Results: 1 - 10 of 1975 matches for " Norman Pavelka "
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AMDA: an R package for the automated microarray data analysis
Mattia Pelizzola, Norman Pavelka, Maria Foti, Paola Ricciardi-Castagnoli
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-335
Abstract: To address these problems we have developed an automated microarray data analysis (AMDA) software, which provides scientists with an easy and integrated system for the analysis of Affymetrix microarray experiments. AMDA is free and it is available as an R package. It is based on the Bioconductor project that provides a number of powerful bioinformatics and microarray analysis tools. This automated pipeline integrates different functions available in the R and Bioconductor projects with newly developed functions. AMDA covers all of the steps, performing a full data analysis, including image analysis, quality controls, normalization, selection of differentially expressed genes, clustering, correspondence analysis and functional evaluation. Finally a LaTEX document is dynamically generated depending on the performed analysis steps. The generated report contains comments and analysis results as well as the references to several files for a deeper investigation.AMDA is freely available as an R package under the GPL license. The package as well as an example analysis report can be downloaded in the Services/Bioinformatics section of the Genopolis http://www.genopolis.it/ webciteMicroarrays have become common tools in many life-science laboratories. Despite their diffusion, it is still not easy to analyze the huge amount of data generated by this powerful technology. Microarray data analysis is in fact a multi-step procedure, and an overwhelming amount of different published methods exist for each step. While the research community has yet to agree on a golden standard, some methods have already been shown to be more appropriate in some situations [1]. On one hand, biologists that need to analyze their own microarray dataset may lack the necessary computational and statistical knowledge to address all aspects of a typical analysis work-flow. On the other hand, service providers that provide data analysis support to their user, have to face the challenge of transferring all
How Do Human Cells React to the Absence of Mitochondrial DNA?
Rossana Mineri,Norman Pavelka,Erika Fernandez-Vizarra,Paola Ricciardi-Castagnoli,Massimo Zeviani,Valeria Tiranti
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0005713
Abstract: Mitochondrial biogenesis is under the control of two different genetic systems: the nuclear genome (nDNA) and the mitochondrial genome (mtDNA). The mtDNA is a circular genome of 16.6 kb encoding 13 of the approximately 90 subunits that form the respiratory chain, the remaining ones being encoded by the nDNA. Eukaryotic cells are able to monitor and respond to changes in mitochondrial function through alterations in nuclear gene expression, a phenomenon first defined in yeast and known as retrograde regulation. To investigate how the cellular transcriptome is modified in response to the absence of mtDNA, we used Affymetrix HG-U133A GeneChip arrays to study the gene expression profile of two human cell lines, 143BTK? and A549, which had been entirely depleted of mtDNA (ρ° cells), and compared it with that of corresponding undepleted parental cells (ρ+ cells).
A power law global error model for the identification of differentially expressed genes in microarray data
Norman Pavelka, Mattia Pelizzola, Caterina Vizzardelli, Monica Capozzoli, Andrea Splendiani, Francesca Granucci, Paola Ricciardi-Castagnoli
BMC Bioinformatics , 2004, DOI: 10.1186/1471-2105-5-203
Abstract: In the present work we used data generated by our lab as well as publicly available data sets to show that dispersion of repeated measures depends on location of the measures themselves following a power law. This enables us to construct a power law global error model (PLGEM) that is applicable to various Affymetrix GeneChip data sets. A new DEG identification method is therefore proposed, consisting of a statistic designed to make explicit use of model-derived measurement spread estimates and a resampling-based hypothesis testing algorithm.The new method provides a control of the false positive rate, a good sensitivity vs. specificity trade-off and consistent results with varying number of replicates and even using single samples.DNA microarrays have become common tools for monitoring genome-wide expression in biological samples harvested under different physiological, pathological or pharmacological conditions. One of the most challenging problems in microarray data analysis is probably the identification of differentially expressed genes (DEG) when comparing distinct experimental conditions. In spite of its biological relevance, there is still no commonly accepted way to answer this question.An ideal DEG identification method should limit both false positives, i.e. genes wrongly called significant (type 1 errors), and false negatives, i.e. genes wrongly called not significant (type 2 errors). To this end, understanding how gene expression values measured in replicated experiments are spread around the true expression level of each gene, would help to distinguish biologically relevant gene expression changes from fluctuations due to different sources of variability that are unrelated to the biological phenomenon under investigation. Measurement error estimates can be obtained in two ways: either by empirically inferring noise from highly replicated data or by deducing noise from a theoretical error model [1]. Especially when the experimental design requires the in
Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast
Jin Zhu equal contributor,Norman Pavelka equal contributor,William D. Bradford,Giulia Rancati equal contributor ,Rong Li
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002719
Abstract: Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e. the propensity of gaining and losing chromosomes at a high frequency. Here we have investigated ploidy- and chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and 2N obtained through a random meiotic process. The aneuploid strains exhibited various levels of whole-chromosome instability (i.e. chromosome gains and losses). CIN correlates with cellular ploidy in an unexpected way: cells with a chromosomal content close to the haploid state are significantly more stable than cells displaying an apparent ploidy between 1.5 and 2N. We propose that the capacity for accurate chromosome segregation by the mitotic system does not scale continuously with an increasing number of chromosomes, but may occur via discrete steps each time a full set of chromosomes is added to the genome. On top of such general ploidy-related effect, CIN is also associated with the presence of specific aneuploid chromosomes as well as dosage imbalance between specific chromosome pairs. Our findings potentially help reconcile the divide between gene-centric versus genome-centric theories in cancer evolution.
Correction: Cytoskeletal Rearrangements in Synovial Fibroblasts as a Novel Pathophysiological Determinant of Modeled Rheumatoid Arthritis
Vassilis Aidinis,Piero Carninci,Maria Armaka,Walter Witke,Vaggelis Harokopos,Norman Pavelka,Dirk Koczan,Christos Argyropoulos,Maung-Maung Thwin,Steffen M?ller,Kazunori Waki,Ponnampalam Gopalakrishnakone,Paola Ricciardi-Castagnoli,Hans-Jürgen Thiesen,Yoshihide Hayashizaki,George Kollias
PLOS Genetics , 2005, DOI: 10.1371/journal.pgen.0010073
Cytoskeletal Rearrangements in Synovial Fibroblasts as a Novel Pathophysiological Determinant of Modeled Rheumatoid Arthritis
Vassilis Aidinis ,Piero Carninci,Maria Armaka,Walter Witke,Vaggelis Harokopos,Norman Pavelka,Dirk Koczan,Christos Argyropoulos,Maung-Maung Thwin,Steffen M?ller,Waki Kazunori,Ponnampalam Gopalakrishnakone,Paola Ricciardi-Castagnoli,Hans-Jürgen Thiesen,Yoshihide Hayashizaki,George Kollias
PLOS Genetics , 2005, DOI: 10.1371/journal.pgen.0010048
Abstract: Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology–assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.
The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast
Fabien Cottier,Martine Raymond,Oliver Kurzai,Marianne Bolstad,Worraanong Leewattanapasuk,Claudia Jiménez-López,Michael C. Lorenz,Dominique Sanglard,Libu?e Váchová,Norman Pavelka,Zdena Palková,Fritz A. Mühlschlegel
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002485
Abstract: Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture.
What can Software Engineers Learn from Manufacturing to Improve Software Process and Product?  [PDF]
Intelligent Information Management (IIM) , 2009, DOI: 10.4236/iim.2009.12015
Abstract: The purpose of this paper is to provide the software engineer with tools from the field of manufacturing as an aid to improving software process and product quality. Process involves classical manufacturing methods, such as statistical quality control applied to product testing, which is designed to monitor and correct the process when the process yields product quality that fails to meet specifications. Product quality is measured by metrics, such as failure count occurring on software during testing. When the process and product quality are out of control, we show what remedial action to take to bring both the process and product under control. NASA Space Shuttle failure data are used to illustrate the process methods.
Blind Trust in the Care-Giver: Is Paternalism Essential to the Health-Seeking Behavior of Patients in Sub-Saharan Africa?  [PDF]
Ishmael Norman
Advances in Applied Sociology (AASoci) , 2015, DOI: 10.4236/aasoci.2015.52008
Abstract: In the past, patients put their lives in the care of doctors in blind trust that the doctors would care for them. This kind of trust is no longer common particularly in the western industrialized nations but the same cannot be said about patients in Ghana and Sub-Sahara Africa. The first concern was whether paternalism was essential in medical practice in Ghana. The second was whether paternalism as an ethical standard should be considered from the ethical lens of the western industrialized nations, rather than from the African cultural context. This entailed a review and examination of the literature on paternalism. We searched databases such as PubMed, Medline and others for reports, editorials and published papers in the English Language. A search on Goggle Scholar on “paternalism in medical practice in Africa” yielded over 380,000 entries and “paternalism in medical practice in Ghana” yielded 2.1 million but more than 99% were not relevant in each instant. Hand searching of selected printed journals and grey literature such as technical reports, conference proceedings and workshops were also assessed. The studies that met the inclusion criteria were given additional review but those with poor methodology were excluded but discussed in this review. I assigned an overall score and identified the position taken in the publication or report in relation to the objectives and rated them objectively. The papers that received scores above 2.5 out of 4 in the evaluation were further analyzed. I summarized the findings into their respective units, and interpreted them based upon my skills, knowledge and specialization in medico-legal ethics, public health and law. The result shows that not enough research has been done on whether or not paternalism should be encouraged as a regular feature of medical practice in Ghana due to the lack of education. It also shows that paternalism enhances the health seeking behavior of patients despite developments on patient autonomy and capacity. Where the average patient is illiterate in general and in medical matters, the paternalism of the physician may be inevitable. Ethical standards such as Informed Consent, Autonomy, Due Process, Benevolence and No malfeasance should be defined and operationalized in clinical practice within the cultural context of Sub-Sahara Africa. A systematic indigenization of medico-legal ethical concerns in medical practice is needed in Ghana.
Define “Social Exclusion”, Articulate Realistic Benchmarks and Evaluation Modalities for the Livelihood Empowerment against Poverty Program, Ghana  [PDF]
Ishmael Norman
Advances in Applied Sociology (AASoci) , 2017, DOI: 10.4236/aasoci.2017.71002
Abstract: The Livelihood Empowerment Against Poverty, a “flagship” program of Ghana, has been praised as a Sub-Saharan Africa’s “miracle cure” for poverty alleviation because it gives US$4.00 - 6.00 a month to a single beneficiary household. In any other regions of the world, the paltry sum would not be praiseworthy. This paper reviewed the literature on the Livelihood Empowerment Against Poverty program to identify the reported gains by beneficiaries. Using government’s own publication on LEAP, the author sought to determine evidence of exclusion of the extreme poor, and to find if the alleged gains under LEAP have improved the social inclusion and functionings of the beneficiary households by reducing the alleged social exclusion, chronic poverty and deprivation or by improving social solidarity and equal opportunities for the beneficiaries. Internet search of pertinent literature was conducted, with hand searching of grey literature produced by the Ghana Ministry of Women and Children Affairs and others on the matter. The pertinent papers that addressed the research questions were read and briefed for analyses. The published literature reveals that the program has not significantly improved the capabilities, functionings and being of beneficiaries, though there is a plethora of anecdotal reportage about improvements in their lives. In rural Ghana poverty is not the basis for social exclusion, though disability is. The loose eligibility criteria reward undeserving recipients of LEAP. The government of Ghana and its development partners need to conduct monitoring and evaluation exercise of the program to assess the contributions, if any. They also need to have a working definition of social exclusion, social isolation and solidarity in order to identify the types of exclusions that should inform policy and intervention. There is an urgent need to redesign the program, rearticulate the eligibility criteria and to set clear pathways for capacity building of the beneficiary household leaders towards productive activities.
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