82 research outputs found
Using Topological Data Analysis for diagnosis pulmonary embolism
Pulmonary Embolism (PE) is a common and potentially lethal condition. Most
patients die within the first few hours from the event. Despite diagnostic
advances, delays and underdiagnosis in PE are common.To increase the diagnostic
performance in PE, current diagnostic work-up of patients with suspected acute
pulmonary embolism usually starts with the assessment of clinical pretest
probability using plasma d-Dimer measurement and clinical prediction rules. The
most validated and widely used clinical decision rules are the Wells and Geneva
Revised scores. We aimed to develop a new clinical prediction rule (CPR) for PE
based on topological data analysis and artificial neural network. Filter or
wrapper methods for features reduction cannot be applied to our dataset: the
application of these algorithms can only be performed on datasets without
missing data. Instead, we applied Topological data analysis (TDA) to overcome
the hurdle of processing datasets with null values missing data. A topological
network was developed using the Iris software (Ayasdi, Inc., Palo Alto). The PE
patient topology identified two ares in the pathological group and hence two
distinct clusters of PE patient populations. Additionally, the topological
netowrk detected several sub-groups among healthy patients that likely are
affected with non-PE diseases. TDA was further utilized to identify key
features which are best associated as diagnostic factors for PE and used this
information to define the input space for a back-propagation artificial neural
network (BP-ANN). It is shown that the area under curve (AUC) of BP-ANN is
greater than the AUCs of the scores (Wells and revised Geneva) used among
physicians. The results demonstrate topological data analysis and the BP-ANN,
when used in combination, can produce better predictive models than Wells or
revised Geneva scores system for the analyzed cohortComment: 18 pages, 5 figures, 6 tables. arXiv admin note: text overlap with
arXiv:cs/0308031 by other authors without attributio
Unilateral Multicentric Breast Cancer
Clinical characteristics of unilateral multicentric breast cancer (UMBC) were explored
depending on aggressiveness, survival rate, disease-free period and local recurrence.
The study included 296 women with breast cancer, surgically treated between 1990 and
2001. UMBC was histologically proved in 29 (9.8%) patients. Multicentricity was defined
by following criteria: a) tumor with minimum one satellite node in the same or
other quadrant of the breast; b) minimum one cut through the breast without tumor
cells; c) histopathologically, discontinued tumors with intra-ductal invasion. The average
age of patients was 63.4 (range 36–85). There were 9 (31.0%) women with one satellite
node, 7 (24.1%) women with two satellite nodes, and 13 (44.8%) women with three or
more satellite nodes. At the operation, axilla was positive in 20 (68.9%) women. Steroid
receptors were highly positive in 12 (41.4%) patients. Primary and secondary tumors
were of the same histological type in 26 (89.6%) patients. Local recurrence was found in
only 3 (10.3%) patients. A five-year period without disease was achieved in 24 (82.7%)
women. Kaplan-Meier analysis showed a significantly higher survival rate at lower tumor
stages (I or II) unlike in advanced stages with predominantly N2 grade. The results
of this study showed a slightly lower five-year disease-free period than in the case of patients
with monocentric breast cancer (MOBC). The survival rate was significantly lower
at all advanced stages, especially determined by N2 axilla. Therefore, the conclusion
is that multicentricity doesn’t increase the risk of poor prognosis, especially at lower
tumor stages
Non-invasive analysis of intestinal development in preterm and term infants using RNA-Sequencing
The state and development of the intestinal epithelium is vital for infant health, and increased understanding in this area has been limited by an inability to directly assess epithelial cell biology in the healthy newborn intestine. To that end, we have developed a novel, noninvasive, molecular approach that utilizes next generation RNA sequencing on stool samples containing intact epithelial cells for the purpose of quantifying intestinal gene expression. We then applied this technique to compare host gene expression in healthy term and extremely preterm infants. Bioinformatic analyses demonstrate repeatable detection of human mRNA expression, and network analysis shows immune cell function and inflammation pathways to be up-regulated in preterm infants. This study provides incontrovertible evidence that whole-genome sequencing of stool-derived RNA can be used to examine the neonatal host epithelial transcriptome in infants, which opens up opportunities for sequential monitoring of gut gene expression in response to dietary or therapeutic interventions
A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response
BACKGROUND: Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly affecting the health and well-being of the host. Thus, it is important to develop a synthetic approach to study the host transcriptome and the microbiome simultaneously. Early microbial colonization in infants is critically important for directing neonatal intestinal and immune development, and is especially attractive for studying the development of human-commensal interactions. Here we report the results from a simultaneous study of the gut microbiome and host epithelial transcriptome of three-month-old exclusively breast- and formula-fed infants. RESULTS: Variation in both host mRNA expression and the microbiome phylogenetic and functional profiles was observed between breast- and formula-fed infants. To examine the interdependent relationship between host epithelial cell gene expression and bacterial metagenomic-based profiles, the host transcriptome and functionally profiled microbiome data were subjected to novel multivariate statistical analyses. Gut microbiota metagenome virulence characteristics concurrently varied with immunity-related gene expression in epithelial cells between the formula-fed and the breast-fed infants. CONCLUSIONS: Our data provide insight into the integrated responses of the host transcriptome and microbiome to dietary substrates in the early neonatal period. We demonstrate that differences in diet can affect, via gut colonization, host expression of genes associated with the innate immune system. Furthermore, the methodology presented in this study can be adapted to assess other host-commensal and host-pathogen interactions using genomic and transcriptomic data, providing a synthetic genomics-based picture of host-commensal relationships
Diamagnetic Persistent Currents and Spontaneous Time-Reversal Symmetry Breaking in Mesoscopic Structures
Recently, new strongly interacting phases have been uncovered in mesoscopic
systems with chaotic scattering at the boundaries by two of the present authors
and R. Shankar. This analysis is reliable when the dimensionless conductance of
the system is large, and is nonperturbative in both disorder and interactions.
The new phases are the mesoscopic analogue of spontaneous distortions of the
Fermi surface induced by interactions in bulk systems and can occur in any
Fermi liquid channel with angular momentum . Here we show that the phase
with even has a diamagnetic persistent current (seen experimentally but
mysterious theoretically), while that with odd can be driven through a
transition which spontaneously breaks time-reversal symmetry by increasing the
coupling to dissipative leads.Comment: 4 pages, three eps figure
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
A Solvable Regime of Disorder and Interactions in Ballistic Nanostructures, Part I: Consequences for Coulomb Blockade
We provide a framework for analyzing the problem of interacting electrons in
a ballistic quantum dot with chaotic boundary conditions within an energy
(the Thouless energy) of the Fermi energy. Within this window we show that the
interactions can be characterized by Landau Fermi liquid parameters. When ,
the dimensionless conductance of the dot, is large, we find that the disordered
interacting problem can be solved in a saddle-point approximation which becomes
exact as (as in a large-N theory). The infinite theory shows a
transition to a strong-coupling phase characterized by the same order parameter
as in the Pomeranchuk transition in clean systems (a spontaneous
interaction-induced Fermi surface distortion), but smeared and pinned by
disorder. At finite , the two phases and critical point evolve into three
regimes in the plane -- weak- and strong-coupling regimes separated
by crossover lines from a quantum-critical regime controlled by the quantum
critical point. In the strong-coupling and quantum-critical regions, the
quasiparticle acquires a width of the same order as the level spacing
within a few 's of the Fermi energy due to coupling to collective
excitations. In the strong coupling regime if is odd, the dot will (if
isolated) cross over from the orthogonal to unitary ensemble for an
exponentially small external flux, or will (if strongly coupled to leads) break
time-reversal symmetry spontaneously.Comment: 33 pages, 14 figures. Very minor changes. We have clarified that we
are treating charge-channel instabilities in spinful systems, leaving
spin-channel instabilities for future work. No substantive results are
change
Analysis of cancer metabolism with high-throughput technologies
<p>Abstract</p> <p>Background</p> <p>Recent advances in genomics and proteomics have allowed us to study the nuances of the Warburg effect – a long-standing puzzle in cancer energy metabolism – at an unprecedented level of detail. While modern next-generation sequencing technologies are extremely powerful, the lack of appropriate data analysis tools makes this study difficult. To meet this challenge, we developed a novel application for comparative analysis of gene expression and visualization of RNA-Seq data.</p> <p>Results</p> <p>We analyzed two biological samples (normal human brain tissue and human cancer cell lines) with high-energy, metabolic requirements. We calculated digital topology and the copy number of every expressed transcript. We observed subtle but remarkable qualitative and quantitative differences between the citric acid (TCA) cycle and glycolysis pathways. We found that in the first three steps of the TCA cycle, digital expression of aconitase 2 (<it>ACO2</it>) in the brain exceeded both citrate synthase (<it>CS</it>) and isocitrate dehydrogenase 2 (<it>IDH2</it>), while in cancer cells this trend was quite the opposite. In the glycolysis pathway, all genes showed higher expression levels in cancer cell lines; and most notably, digital gene expression of glyceraldehyde-3-phosphate dehydrogenase (<it>GAPDH</it>) and enolase (<it>ENO</it>) were considerably increased when compared to the brain sample.</p> <p>Conclusions</p> <p>The variations we observed should affect the rates and quantities of ATP production. We expect that the developed tool will provide insights into the subtleties related to the causality between the Warburg effect and neoplastic transformation. Even though we focused on well-known and extensively studied metabolic pathways, the data analysis and visualization pipeline that we developed is particularly valuable as it is global and pathway-independent.</p
The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies
<p>Abstract</p> <p>Background</p> <p>Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists.</p> <p>Results</p> <p>Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan – the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (<it>P</it>) derived from widely used simple <it>t</it>-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent <it>P</it>-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on <it>P</it>-value ranking is an expected mathematical consequence of the high variability of the <it>t</it>-values; the more stringent the <it>P</it>-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations.</p> <p>Conclusion</p> <p>We recommend the use of FC-ranking plus a non-stringent <it>P </it>cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the <it>P</it>-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and <it>P</it>-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the <it>P </it>criterion balances sensitivity and specificity.</p
A highly hydrophilic water-insoluble nanofiber composite as an efficient and easily-handleable adsorbent for the rapid adsorption of cesium from radioactive wastewater
Herein, we report a new Prussian blue nanoparticle (PBNPs) incorporated polyvinyl alcohol (PVA) composite nanofiber (c-PBNPs/PVA) for the rapid adsorption of cesium (Cs) from radioactive wastewater. Initially, various electrospinning parameters such as solvent, PVA wt%, PBNPs wt% and glutaraldehyde (GA) wt% were extensively optimized to obtain a better physicochemical property of the c-PBNPs/PVA. In order to improve the water insoluble nature of the PVA, post cross-linking was carried out for the c-PBNPs/PVA using glutaraldehyde (GA) and HCl vapor as the cross-linker and catalyst, respectively. SEM images revealed the smooth and continuous morphology of the c-PBNPs/PVA composite nanofibers with diameters of 200–300 nm and lengths up to several millimeters. TEM images confirmed homogeneous dispersion and good incorporation of PBNPs into the PVA matrix. The amorphous nature of the c-PBNPs/PVA was confirmed by the XRD analysis. FT-IR spectra showed successful cross-linking of PVA with GA. It was found that the prepared composite nanofiber is highly hydrophilic and water-insoluble. The c-PBNPs/PVA showed an excellent and faster Cs adsorption rate of 96% after only 100 min. These results are comparable to those previously reported. After the Cs adsorption test, the c-PBNPs/PVA composite nanofiber can be easily separated from the wastewater.ArticleRSC ADVANCES. 4(103):59571-59578 (2014)journal articl
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