Kerfuffle: a web tool for multi-species gene colocalization analysis

The evolutionary pressures that underlie the large-scale functional organization of the genome are not well understood in eukaryotes. Recent evidence suggests that functionally similar genes may colocalize (cluster) in the eukaryotic genome, suggesting the role of chromatin-level gene regulation in shaping the physical distribution of coordinated genes. However, few of the bioinformatic tools currently available allow for a systematic study of gene colocalization across several, evolutionarily distant species. Kerfuffle is a web tool designed to help discover, visualize, and quantify the physical organization of genomes by identifying significant gene colocalization and conservation across the assembled genomes of available species (currently up to 47, from humans to worms). Kerfuffle only requires the user to specify a list of human genes and the names of other species of interest. Without further input from the user, the software queries the e!Ensembl BioMart server to obtain positional information and discovers homology relations in all genes and species specified. Using this information, Kerfuffle performs a multi-species clustering analysis, presents downloadable lists of clustered genes, performs Monte Carlo statistical significance calculations, estimates how conserved gene clusters are across species, plots histograms and interactive graphs, allows users to save their queries, and generates a downloadable visualization of the clusters using the Circos software. These analyses may be used to further explore the functional roles of gene clusters by interrogating the enriched molecular pathways associated with each cluster.Comment: BMC Bioinformatics, In pres

N-cross coupled phase locked loops

Interference cancelation has been mainly performed using arrays, in an important issue in communication both array and spatial cancelation and time domain approach were used. In array applications, depth of cancelation may dependent on the interferences to background power ratio and their spatial distributions. Also, array cancelers are inadequate when the signals are less than an array beamwidth apart. The latter was dealt with using supperesolution and eigenanalysis methods. Different time domain methods were used in the past. Among them what is termed Cross-Coupled PEL. It is an arrangement of two PLL each one is locked on and tracking one signal of the two at the input. In fact the output of such a system is dependent on one signal or the other. In a way Cross-Coupled IPLL is a signal separator. For the case of more than two signals we proposed in this thesis the N-Cross Coupled PLL. It is used to receive and process one of the N signals while suppressing the others which could be looked upon as interchannel interference. N-Cross Coupled PLLs consist of N PLLs interconnected using amplitude control loops that estimate the instantaneous amplitude of each signal. N-i signals are then subtracted from the input to leave, as clear as possible, one signal to be handled by the corresponding PLL. If the PLLs are used as FM demodulators then we get at the output the information contained in each signal regardless of the signal\u27s relative powers and or their modulation content. Thus N-Cross Coupled PLLs behaves as N signals separator

Systems approach to the design of locomotive fatigue management technologies

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2006.Includes bibliographical references (p. 145-148).Falling asleep while operating a vehicle leads to serious accidents and loss of lives. The challenge of detecting drowsiness nonintrusively stems from the absence of a single marker, and the existence of diverse signs and symptoms that collectively but not uniquely characterize it. Current alerters for locomotive cabs are inadequate partly because they a) often monitor one modality b) fail to consider the inherent characteristics of the locomotive operator tasks and physical environment, and c) are typically developed without quantitative techniques to assess performance and optimize components as part of an overall system, rather than at the individual level. Based on an estimation theory framework, a new systems approach is here proposed to design locomotive cab alerting technologies. The main idea is to combine information from an infrared eyelid monitor and a generic Train Sentry class activity monitor, to isolate the common drowsiness component and obtain an improved estimate of the operator's state. A study first quantified the important physical aspects of the locomotive cab and engineer behavior pertinent to the performance of image-based eye closure monitors.(cont.) A bench test study evaluated Attention Technology's current infrared eye closure monitor prototype front-end image analysis, Model DD-850, to verify whether its performance was a good match to the locomotive physical environment and engineer behavioral characteristics. Data from these studies were used to develop a simulation software tool in MATLAB/SIMULINK. The goal was to assess the proposed tandem detector solution and to support rational design, development and optimization of future locomotive alerting systems. A signal detection theory (SDT) approach was employed. However, the detectors were nonlinear, had multiple alerting levels and displayed non-Gaussian noise characteristics. Therefore, Monte Carlo methods were used to compute their SDT parameters on both a standalone and tandem basis. Investigation through simulation showed that adopting an architecture using tandem detectors and an "AND" logic based arbiter reduces the false alarm rate by an order of magnitude and improves the total time to alert, at the expense of only a few percent in missed alarm probability. Detection performance may be further enhanced using a speed dependent arbiter with "AND" logic above a speed threshold and "OR" logic below it.(cont.) In the simulation, the speed threshold was found to be 25 mph. This system-level study provides enough ground to build a prototype system and test the proposed solution in a simulator. Supported by FRA through Department of Transportation Volpe Research Center Contract DTRS57-04-Q-80164 PR 79-3354 and by a Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada.by Anton Aboukhalil.S.M

Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos

Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses, and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here, we have developed ‘enhancer-FACS-Seq’ (eFS) technology for highly parallel identification of active, tissue-specific enhancers in Drosophila embryos. Analysis of enhancers identified by eFS to be active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, novel mesodermal transcription factors (TFs). Naïve Bayes classifiers using TF binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded within them

C/EBP alpha and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor

Acute erythroid leukemia (AEL) commonly involves both myeloid and erythroid lineage transformation. However, the mutations that cause AEL and the cell(s) that sustain the bilineage leukemia phenotype remain unknown. We here show that combined biallelic Cebpa and Gata2 zinc finger-1 (ZnF1) mutations cooperatively induce bilineage AEL, and that the major leukemia-initiating cell (LIC) population has a neutrophil-monocyte progenitor (NMP) phenotype. In pre-leukemic NMPs Cebpa and Gata2 mutations synergize by increasing erythroid transcription factor (TF) expression and erythroid TF chromatin access, respectively, thereby installing ectopic erythroid potential. This erythroid-permissive chromatin conformation is retained in bilineage LICs. These results demonstrate that synergistic transcriptional and epigenetic reprogramming by leukemia-initiating mutations can generate neomorphic pre-leukemic progenitors, defining the lineage identity of the resulting leukemia

High-coverage sequencing and annotated assemblies of the budgerigar genome

BACKGROUND: Parrots belong to a group of behaviorally advanced vertebrates and have an advanced ability of vocal learning relative to other vocal-learning birds. They can imitate human speech, synchronize their body movements to a rhythmic beat, and understand complex concepts of referential meaning to sounds. However, little is known about the genetics of these traits. Elucidating the genetic bases would require whole genome sequencing and a robust assembly of a parrot genome. FINDINGS: We present a genomic resource for the budgerigar, an Australian Parakeet (Melopsittacus undulatus) -- the most widely studied parrot species in neuroscience and behavior. We present genomic sequence data that includes over 300x raw read coverage from multiple sequencing technologies and chromosome optical maps from a single male animal. The reads and optical maps were used to create three hybrid assemblies representing some of the largest genomic scaffolds to date for a bird; two of which were annotated based on similarities to reference sets of non-redundant human, zebra finch and chicken proteins, and budgerigar transcriptome sequence assemblies. The sequence reads for this project were in part generated and used for both the Assemblathon 2 competition and the first de novo assembly of a giga-scale vertebrate genome utilizing PacBio single-molecule sequencing. CONCLUSIONS: Across several quality metrics, these budgerigar assemblies are comparable to or better than the chicken and zebra finch genome assemblies built from traditional Sanger sequencing reads, and are sufficient to analyze regions that are difficult to sequence and assemble, including those not yet assembled in prior bird genomes, and promoter regions of genes differentially regulated in vocal learning brain regions. This work provides valuable data and material for genome technology development and for investigating the genomics of complex behavioral traits

Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score

AbstractIntroductionFew tools predict survival from pancreatic cancer (PAC). The McGill Brisbane Symptom Score (MBSS) based on symptoms at presentation (weight loss, pain, jaundice and smoking) was recently validated. The present study compares the ability of four strategies to predict 9-month survival: MBSS, carbohydrate antigen 19-9 (CA 19-9) alone, CA19-9-to-bilirubin ratio and a combination of MBSS and the CA19-9-to-bilirubin ratio.MethodologyA retrospective review of 133 patients diagnosed with PAC between 2005 and 2011 was performed. Survival was determined from the Quebec civil registry. Blood CA 19-9 and bilirubin values were collected (n = 52) at the time of diagnosis. Receiver-operating characteristic (ROC) curves were used to determine a cutoff for optimal test characteristics of CA 19-9 and CA19-9-to-total bilirubin ratio in predicting survival at 9 months. Predictive characteristics were then calculated for the four strategies.ResultsOf the four strategies, the one with the greatest negative predictive value was the MBSS: negative predictive value (NPV) was 90.2% (76.9–97.3%) and the positive likelihood ratio (LR) was the greatest. The ability of CA 19-9 levels alone, at baseline, to predict survival was low. For the CA19-9-to-bilirubin ratio, the test characteristics improved but remained non-significant. The best performing strategy according to likelihood ratios was the combined MBSS and CA19-9 to the bilirubin ratio.ConclusionCA19-9 levels and the CA19-9-to-bilirubin ratio are poor predictors of survival for PAC, whereas the MBSS is a far better predictor, confirming its clinical value. By adding the CA19-9-to-bilirubin ratio to the MBSS the predictive characteristics improved

Expressions of Multiple Neuronal Dynamics during Sensorimotor Learning in the Motor Cortex of Behaving Monkeys

Previous studies support the notion that sensorimotor learning involves multiple processes. We investigated the neuronal basis of these processes by recording single-unit activity in motor cortex of non-human primates (Macaca fascicularis), during adaptation to force-field perturbations. Perturbed trials (reaching to one direction) were practiced along with unperturbed trials (to other directions). The number of perturbed trials relative to the unperturbed ones was either low or high, in two separate practice schedules. Unsurprisingly, practice under high-rate resulted in faster learning with more pronounced generalization, as compared to the low-rate practice. However, generalization and retention of behavioral and neuronal effects following practice in high-rate were less stable; namely, the faster learning was forgotten faster. We examined two subgroups of cells and showed that, during learning, the changes in firing-rate in one subgroup depended on the number of practiced trials, but not on time. In contrast, changes in the second subgroup depended on time and practice; the changes in firing-rate, following the same number of perturbed trials, were larger under high-rate than low-rate learning. After learning, the neuronal changes gradually decayed. In the first subgroup, the decay pace did not depend on the practice rate, whereas in the second subgroup, the decay pace was greater following high-rate practice. This group shows neuronal representation that mirrors the behavioral performance, evolving faster but also decaying faster at learning under high-rate, as compared to low-rate. The results suggest that the stability of a new learned skill and its neuronal representation are affected by the acquisition schedule.United States-Israel Binational Science FoundationIsrael Science FoundationIda Baruch FundRosetrees Trus