299 research outputs found
High-Resolution Genome-Wide Single Nucleotide Polymorphism Mapping in Acute Myeloid Leukaemia
No full textPhDInvestigation of the genetics of acute myeloid leukaemia (AML) has revealed the underlying
basis of the disease and led to targets for therapy. High-resolution single nucleotide
polymorphism (SNP) arrays detected regions of loss of heterozygosity and DNA copy number
changes, augmenting the results of conventional cytogenetic analysis in AML. Fifteen out of 72
(20%) primary AML samples exhibited large regions of homozygosity that could not be
accounted for by visible chromosomal abnormalities in the karyotype. Further analysis
confirmed that these patterns were due to partial uniparental disomy (UPD). Remission marrow
was available from five patients showing UPD in their leukemias, and in all cases the
homozygosity was found to be restricted to the diagnostic leukemic clone. These cryptic nonrandom
chromosomal abnormalities are characteristic of mitotic recombination. In 7 of 13 cases
with UPD, concurrent homozygous mutations were identified at four distinct loci (WTI, FLT3,
CEBPA, and RUNXI). This implies that mutation precedes mitotic recombination which acts as
a "second hit" responsible for removal of the remaining wild-type allele. Clonal evolution from
heterozygous to homozygous mutations by mitotic recombination would provide a mechanism
for relapse of AML. Analysis of 27 paired diagnostic and relapsed AML samples demonstrated
newly acquired segmental UPDs at relapse in 11 AML samples (40%). Six were segmental
UPDs of chromosome 13q, which led to a change from heterozygosity to homozygosity for
internal tandem duplication of FLT3. Three further AML samples had evidence of acquired
segmental UPD of 13q in a subclone of the relapsed leukemia. One patient acquired segmental
UPD of 19q which led to homozygosity for a CEBPA mutation 207 C-'T. Finally, a single
AML patient acquired segmental UPD of chromosome 4q, for which the candidate gene is
unknown. In conclusion, the acquisition of segmental UPD and the resulting homozygous
mutation is a common event associated with relapse of AML
Sources of visual noise
No full textNoise processes pervade many aspects of visual information processing from photo-transduction on. But it is not known whether all this noise affects the observer\u27s visual sensitivity. To study this issue, I have employed equivalent input noise measurements to characterize the observer\u27s intrinsic noise along several signal dimensions. The equivalent input noise is the power spectral density of white display noise required to double the threshold contrast energy for a given signal. The existence of multiple, frequency-selective channels in the visual system allows us to choose signals to selectively engage channels tuned to different spatiotemporal frequencies, one at a time, and thereby measure the spectrum of the equivalent input noise. The psychophysically measured spectrum can then be compared to the spectra of known intrinsic noise sources: photon noise (generated by the random way in which light is absorbed by photoreceptors), ganglion cell noise, and cortical noise.
The observer\u27s equivalent input noise was measured as a function of letter size (or grating spatial frequency), signal duration, and retinal illuminance both in the fovea and periphery using an identification task. The results indicate that the limiting noise in scotopic vision is indeed the photon noise. Photon noise also limits the visibility of high spatiotemporal frequency signals at photopic and low-mesopic light levels. But, the limiting noise for low spatiotemporal frequency signals, in both the fovea and the periphery, has the characteristics of neural noise
Polarimetric radar modeling of mixtures of precipitation particles
No full textWith the recent advances of dual-polarized radar techniques in meteorology it is now possible to deduce precipitation microphysical characteristics in far more detail than possible with reflectivity measurements alone. Radar parameters such as differential reflectivity and differential phase between horizontal and vertical polarizations have been studied in detail as well as linear depolarization ratio, copolar correlation coefficient, and backscatter differential phase. While these parameters can be linked to certain microphysical properties of specific classes of precipitation such as raindrops or hail, very little study has been directed at the practically important cases of mixtures of different types of precipitation particles such as rain, hail, graupel, ice crystals, and snow. Each type can have different size, shape, orientation, and dielectric constant distributions. The treatment here is rigorous and is based on the Mueller matrix formulation. Radar parameters are derived from the averaged Mueller matrix computations. Careful consideration is given to the orientation and size distributions of the different particle types. After calculating single particle scattering characteristics, some simple two-component mixtures such as rain/hail and ice crystals/snow are considered. Finally, a 2D numerical cloud model is used to simulate the rain, hail/graupel, and snow fields of an evolving convective storm from which the radar parameters are derived for the initial, peak, and dissipating stages of the storm. Model computations are performed at C and S-band frequencies.This work was supported by the FAA under Contract DTFA01-90-Z-02005 and the National Science Foundation under Contract ATM-9214864. The work of R. Raghavan was also supported by NASA through USRA under Contract NAS8-37140. The National Center for Atmospheric Research is sponsored by the National Science Foundation
Which patients with acute myeloid leukemia in CR1 can be spared an allogeneic transplant?
No full textPurpose of reviewDisease relapse remains the major cause of treatment failure in adults with acute myeloid leukemia (AML) in first complete remission (CR1) treated with intensive chemotherapy alone. Allogeneic stem cell transplantation (allo-SCT) reduces the risk of disease recurrence, and thus the advent of reduced intensity-conditioning regimens coupled with increased donor availability has increased the deliverability of potentially curative transplant therapy in AML. However, allo-SCT remains associated with significant additional morbidity and mortality, and it is therefore important to identify patients whose outcome if treated with chemotherapy alone is good enough to spare them the risks associated with allo-SCT.Recent findingsCharacterization of cytogenetic and molecular abnormalities present at diagnosis coupled with dynamic assessments of measurable residual disease now permit greater accuracy in defining the relapse risk in patients treated with chemotherapy alone. At the same time, the risk of transplant-related mortality can be predicted by a number of scoring systems which assess patient comorbidity. Taken together, such assessments permit a dynamic assessment of the risks and benefits of transplantation aiding the identification of patients who are unlikely to benefit from transplantation in CR1.SummaryIncreasingly accurate risk stratification in adults with AML CR1 aids the rational utilization of allo-SCT. Future research integrating the results of serial MRD analysis in molecularly defined subtypes of AML will further improve rational selection of patients for transplant.</p
Project Management Learnings from Ramayana
No full textRamayana is the first Indian Epic also known as Adhi Kavya comprising 24000 shlokas, grouped in 500 sargaswhich are divided over 7 kandas. The first author of Ramayana, written in Sanskrit, is Maharishi Valmiki. These authors have discovered multiple dimensions and implications of Ramayana in diverse fields like Management, Philosophy, Spirituality, Literature, Indian Mythology, etc. There are many teachings from this epic that can be applied in today's management-life in areas such as Project Management, Strategic Management, Leadership, Human Resource Management, and the like. In Ramayana, after the evil-spirited Ravana abducted Goddess Sita, Lord Rama who is in search of Goddess Sita, along with his brother, Lakshmana finds Lord Hanuman, a noble monkey, who played a predominant role in search of Goddess Sita and destruction of Ravana, the king of Lanka. After finding the whereabouts of Goddess Sita, they prepared for a war with Ravana to bring her back to Ayodhya. They also prepared for the Coronation of Lord Rama; so that" the Prince in exile becomes the King of Ayodhya". Objective: The application of Agile Project Management at the time of searching Goddess Sita in Ramayana. Methodology: Agile Project Management methodology is used in this research study, which has four main stages: Project Initiation, Project Planning, Project Execution, and Project Closure The research study tries to understand in detail how Ramayana's knowledge-repository is integrated into the modern-day Agile Project Management Methodology. Results: Valmiki Ramayana is extremely wealthy in portraying multiple examples of Project Management methodologies, synthesizing of Agile Project Methodologies from Ramayana, and application of Project Management to modern-day Projects. Implications: The results from this article can be applied to today's management life like – Project Management, Strategic Management, Leadership, and Human Resource Management
A Self-Organizing Neural Network For Locus-Addressable Associative Memory
No full textA Self-organizing neural network model for locus-Addressable associative memory, and binary pattern recognition is presented. The net may be used for either auto-associative or hetero-associative tasks. Locus - addressability is suggested as a possible mechanism for retrieval of memories without any external cues in the form of partial or corrupted exemplar patterns. The architecture, Which employs competitive dynamics, embodies a parallel search scheme which updates itself adaptively as the learning progresses. A thresholding mechanism ensures the learning of new exemplars. On saturation of the memory capacity, the net thereafter responds to new patterns by recalling exemplars in its memory that are nearest to the presented input in Hamming distance. The stability – Plasticity problem is overcome by ‘fast learning’ and irreversibility of connection-weight changes. This architecture overcomes the orthogonality and linear independence constraints that limit other models
Patentopia: A multi-stage patent extraction platform with disambiguation for certain semantic challenges
No full textBibliographic name disambiguation is an major semantic challenge, but critical to social sciences studies of important intellectual assets. Here we contribute to innovation research in several ways. We show a significant synonym problem in author names and discuss how a pre-processing heuristic step standardizing name variants helps, but homonyms generated with Chinese names are particularly difficult to resolve and manifest in an associated location list. Here we identify a new phenomenon of "onomastic profusion," the frequent use of certain words in firm names for semantic reasons that can confound disambiguation clustering algorithms. We illustrate these concerns with Patentopia, our customized platform accessing the PatentsView portal for the United States Patent and Trademark Office database and available for free academic use. This multi-stage system uses heuristics in concert with the PatentsView clustering process and reports meta-data to further assist analysis. As highly relevant use cases, we illustrate system performance with data derived from two important public innovation programs, I-Corps and Small Business Innovation Research (SBIR), and we close with implications for bibliometric analysis of current patent data.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Delft Centre for Entrepreneurshi
The potential clinical utility of Whole Genome Sequencing for patients with cancer:evaluation of a regional implementation of the 100,000 Genomes Project
No full textBackground: The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom. Methods: A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results. Results: After excluding samples with no sequencing data (1678/4851; 34.6%), 3166 sample sets (germline and somatic) from 3067 participants were sequenced. Results of 1256 participants (41.0%) were interpreted (excluding participants who died (308/3067; 10.0%) or were clinically excluded (1503/3067; 49.0%)). Of these, 323 (25.7%) had no variants in genes which may alter management (Domain 1 genes). Of the remaining 933 participants, 552 (59.2%) had clinical recommendations made (718 recommendations in total). These included therapeutic recommendations (377/933; 40.4%), such as clinical trial, unlicensed or licensed therapies or high TMB recommendations, and germline variants warranting clinical genetics review (85/933; 9.1%). At the last follow up, 20.2% of all recommendations were followed (145/718). However, only a small proportion of therapeutic recommendations were followed (5.1%, 25/491). Conclusions: The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients
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