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From single cells to whole organisms
Silke Sperling
Genome Biology , 2006, DOI: 10.1186/gb-2005-6-13-365
Abstract: Functional genomics aims to provide a bridge from the static information in the genome to the related functional properties of the cell, tissue or organism. Data on a genome-wide level are generated using a variety of high-throughput technologies, and are analyzed using bioinformatics and system-level integration. The program of the recent European Science Foundation Conference on functional genomics linked the most promising developments in functional genomics research and technology with their applications and future in biomedicine.Considerable effort is currently being made to reveal the relationship between complex genotypes and phenotype, for example, in looking at the enormous genetic variation that exists in outbred populations such as our own and how it manifests itself in phenotypic variation. One approach to uncovering the molecular basis of common diseases such as cancer and cardiovascular diseases is the correlation of sequence variation among healthy and ill individuals to try and understand how genetic perturbations interact to affect clinical outcome. Analyzing genotype-phenotype relationships in simpler organisms than humans, Charlie Boone (University of Toronto, Canada) and Andrew Fraser (Wellcome Trust Sanger Institute, Cambridge, UK) reported on global genetic-interaction projects in Saccharomyces cerevisiae and Caenorhabditis elegans that aim to identify overlapping functions and compensatory pathways that complicate the phenotype. Using an automated screen for suppressor/enhancer mutations, Boone's group analyzed 250,000 mutants of S. cerevisiae for synthetic genetic sickness or lethal genotypes, which are important for understanding how an organism tolerates random mutation. Interestingly, the genetic-interaction map appears to be four times as complex as the protein-protein interaction map. Genetic interactions do not overlap with physical interactions, but predict functional neighborhoods and clearly identify components of pathways whose orde
The Discourse on Mental Disorders in the Hispanic Short Novel: Amado Nervo’s case
Sperling, Christian
Asclepio : Revista de Historia de la Medicina y de la Ciencia , 2011,
Abstract: The evolution of Amado Nervo’s novellas shows a constant communication with the paradigmatic shifts in the field of psychopathology. His metafictional constructs foreground a playful treatment of some of medicine’s key ideas. In some cases, the narrow limits of positivistic psychopathology are overcome in order to anticipate notions that obtain scientific status with modern psychology. La evolución de la novela corta de Amado Nervo muestra una comunicación constante con las transformaciones paradigmáticas en el campo de la psicopatología. Las construcciones metaficcionales hacen patente un tratamiento lúdico de algunas ideas clave de la disciplina médica. En algunos casos se superan los estrechos límites de la psicopatología positivista para anticipar planteamientos que adquieren estatuto científico con la psicología moderna.
Transcriptional regulation at a glance
Sperling Silke
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-s6-s2
Abstract: Considering that 80 genomes have been sequenced, providing us with the static information of the genome, it is still a long way to reveal the relationship between complex genotypes and phenotypes. The transcriptional regulation process is one of the obstacles that need to be understood to bridge our current information gap. It describes the first step from the genomic sequence information to RNA templates used for protein production or as direct functional units, like non-coding RNAs (e.g. micro RNAs). This introduction aims to highlight the key aspects of the transcriptional process from our current understanding.
Academic Procrastinators and Their Self-Regulation  [PDF]
Seung Won Park, Rayne A. Sperling
Psychology (PSYCH) , 2012, DOI: 10.4236/psych.2012.31003
Abstract: Previous procrastination research has provided considerable support for procrastination as a failure of self-regulation. However, procrastination has rarely been examined in relation to models of self-regulated learning. The purpose of this study was to understand the motives and reasons for academic procrastination from a self-regulated learning perspective. The current study employed a mixed-methods design in which participants completed several survey instruments of academic procrastination, self-regulation, and academic motivation and participated in semi-structured interviews. Findings indicated that academic procrastination was related to poor self-regulatory skills and defensive behaviors including self-handica- pping strategies. Only limited support for students’ demonstration of procrastination as an adaptive beha- vior (or, active procrastination) was also indicated. Limitations and implications for future research are discussed.
An Algorithm for the Reconstruction of Entrance Beam Fluence from Virtual Patient Exit Electronic Portal Images  [PDF]
Nicholas N. Sperling, E. Ishmael Parsai
International Journal of Medical Physics,Clinical Engineering and Radiation Oncology (IJMPCERO) , 2015, DOI: 10.4236/ijmpcero.2015.42022
Abstract:
The problem of determining the in vivo dosimetry for patients undergoing radiation treatment has been an area of interest since the development of the field. More recent methods of measurement employ Electronic Portal Image Devices (EPID), or dosimeter arrays, for entrance or exit fluence determination. The more recent methods of in vivo dosimetry make use of detector arrays and reconstruction techniques to determine dose throughout the patient volume. One method uses an array of ion chambers located upstream of the patient. This requires a special hardware device and places an additional attenuator in the beam path, which may not be desirable. An alternative to this approach is to use the existing EPID, which is part of most modern linear accelerators, to image the patient using the treatment beam. Methods exist to deconvolve the detector function of the EPID using a series of weighted exponentials [1]. Additionally, this method has been extended to the deconvolution of the patient scatter in order to determine in vivo dosimetry. The method developed here intends to use EPID images and an iterative deconvolution algorithm to reconstruct the impinging primary fluence on the patient. This primary fluence may then be employed, using treatment time volumetric imaging, to determine dose through the entire patient volume. Presented in this paper is the initial discussion of the algorithm, and a theoretical evaluation of its efficacy using montecarlo derived virtual fluence measurements. The results presented here indicate an agreement of 1% dose difference within 95% the field area receiving 10% of the entrance fluence for a set of sample highly modulated fields. These results warrant continued investigation in applying this algorithm to clinical patient treatments.
Pro: Can biomarkers be gold standards in Alzheimer's disease?
Reisa Sperling, Keith Johnson
Alzheimer's Research & Therapy , 2010, DOI: 10.1186/alzrt41
Abstract: The past decade has seen tremendous advances in the development of biomarkers for Alzheimer's disease (AD), raising the question as to whether these markers are now ready to serve as a gold standard. The definitive diagnosis of AD currently requires pathologic confirmation, but it is likely that several of the currently available biomarkers can add sufficient precision to the clinical diagnosis of AD dementia to approach a level of accuracy similar to autopsy diagnosis.Elegant work by Cliff Jack and colleagues has suggested there is a dynamic temporal sequence of biomarkers that evolves over the course of AD, and thus the optimal set of biomarkers for diagnosis and/or tracking progression is probably dependent on the stage of AD [1]. The predictive value of biomarkers early in this sequence is particularly relevant to the widely acknowledged need to move therapeutic interventions earlier in the pathophysiologic process of AD for maximal efficacy. Broadly, these biomarkers can be divided into three categories: evidence of amyloid-β deposition, detected by positron emission tomography (PET) amyloid imaging or cerebrospinal fluid (CSF) markers of Aβ; evidence of synaptic dysfunction, detected by [18F]fluorodeoxyglucose-PET or functional magnetic resonance imaging (MRI); and evidence of neurodegeneration or neuronal loss, detected by CSF tau and atrophy detectable with volumetric MRI. We will briefly review the utility of these biomarkers in clinical diagnosis and research criteria across the continuum from AD dementia back to cognitively normal older individuals who may be in presymptomatic stages of AD.By the stage of AD dementia, there is clear evidence of abnormality in all biomarker categories, including low CSF Aβ and elevated CSF tau, increased PET amyloid tracer retention, [18F]fluorodeoxyglucose hypometabolism, default network disruption on functional MRI, cortical thinning and hippocampal atrophy on volumetric MRI. It is widely acknowledged that a small percen
“The Glacial Question, Unsolved”: A Specimen Commentary on Lines 1-31
Thomas Roebuck,Matthew Sperling
Glossator : Practice and Theory of the Commentary , 2010,
Abstract:
Elucidation of Clathrin-Mediated Endocytosis in Tetrahymena Reveals an Evolutionarily Convergent Recruitment of Dynamin.
Elde,Morgan,Winey,Sperling
PLOS Genetics , 2005,
Abstract: Ciliates, although single-celled organisms, contain numerous subcellular structures and pathways usually associated with metazoans. How this cell biological complexity relates to the evolution of molecular elements is unclear, because features in these cells have been defined mainly at the morphological level. Among these ciliate features are structures resembling clathrin-coated, endocytic pits associated with plasma membrane invaginations called parasomal sacs. The combination of genome-wide sequencing in Tetrahymena thermophila with tools for gene expression and replacement has allowed us to examine this pathway in detail. Here we demonstrate that parasomal sacs are sites of clathrin-dependent endocytosis and that AP-2 localizes to these sites. Unexpectedly, endocytosis in Tetrahymena also involves a protein in the dynamin family, Drp1p (Dynamin-related protein 1). While phylogenetic analysis of AP subunits indicates a primitive origin for clathrin-mediated endocytosis, similar analysis of dynamin-related proteins suggests, strikingly, that the recruitment of dynamin-family proteins to the endocytic pathway occurred independently during the course of the ciliate and metazoan radiations. Consistent with this, our functional analysis suggests that the precise roles of dynamins in endocytosis, as well as the mechanisms of targeting, differ in metazoans and ciliates.
Some thoughts about higt cholesterol in choldren and adolescents
Mark A Sperling
Revista Venezolana de Endocrinología y Metabolismo , 2008,
Abstract:
Prediction and prevention of type 1 diabetes mellitus
Mark A Sperling
Revista Venezolana de Endocrinología y Metabolismo , 2008,
Abstract:
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