995 research outputs found
Discussion of the Requisite Qualities of Lithographic Limestone, with Report on Tests of the Lithographic Stone of Mitchell County, Iowa
Identifying a gene expression signature of cluster headache in blood.
Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (nâ=â19) or chronic (nâ=â20) cluster headache in comparison with headache-free controls (nâ=â20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach
Enhanced gain and output power of a sealedâoff rfâexcited CO2 waveguide laser with goldâplated electrodes
The smallâsignal gain and the laser output power have been measured in a cw sealedâoff rfâexcited CO2waveguide laser for two different electrodematerials, goldâplated copper and aluminum, at several excitation frequencies, gas pressures and mixture compositions. In the case of the goldâplated electrodes an enhancement of the gain up to a factor of 2 and the output power up to a factor of 1.4 with time at a frequency of 190 MHz and 60 Torr of 1:1:5+5% (CO2:N2:He+Xe) mixture is observed. This is believed to be the result of the goldcatalytic activities which are favored by increased electrode temperatures and helium rich gas compositions
Successful treatment of Candida parapsilosis and Pseudomonas aeruginosa infection using medical and surgical management in an injecting drug user with mitral and aortic valve endocarditis: a case report
<p>Abstract</p> <p>Introduction</p> <p>Polymicrobial endocarditis is a well-recognized problem in intravenous drug users and it accounts for 1 to 3% of endocarditis cases overall and up to 9% in other series. The most common combinations of organisms include <it>Staphylococcus aureus</it> and <it>Streptococcus pneumoniae</it> followed by <it>Staphylococcus aureus</it> and <it>Pseudomonas aeruginosa</it>. <it>Candida parapsilosis</it> endocarditis carries a mortality rate of 45%, and each infection with <it>Candida</it> or <it>Pseudomonas</it> endocarditis per se carries a very high mortality rate approaching 85% and 80%, respectively. The combination of <it>P. aeruginosa</it> and <it>C. parapsilosis</it> has never been encountered and there have been no earlier reports of the combination of <it>C. parapsilosis</it> and <it>P. aeruginosa</it> in adult intravenous drug users as a cause of endocarditis.</p> <p>Case presentation</p> <p>We present a 49-year-old man with bivalvular endocarditis with <it>P. aeruginosa</it> and <it>C. parapsilosis</it>. He had a prior bivalvular replacement in 2005 that became infected with the above microorganisms and he was treated with intravenous antibiotics. Because of ongoing intravenous drug use, a second valve replacement was denied. A few days later, the patient presented with septic shock secondary to <it>P. aeruginosa</it> and <it>C. parapsilosis</it> recurrent endocarditis. The infection was cured with a second bivalvular replacement and extended therapy with antibiotics and antifungals.</p> <p>Conclusion</p> <p>This is the first time a patient has presented with <it>P. aeruginosa</it> and <it>C. parapsilosis endocarditis</it>. Relapsing polymicrobial endocarditis can be cured with medical and surgical therapy.</p
Literature-aided meta-analysis of microarray data: a compendium study on muscle development and disease
Background: Comparative analysis of expression microarray studies is difficult due to the large influence of technical factors on experimental outcome. Still, the identified differentially expressed genes may hint at the same biological processes. However, manually curated assignment of genes to biological processes, such as pursued by the Gene Ontology (GO) consortium, is incomplete and limited. We hypothesised that automatic association of genes with biological processes through thesaurus-controlled mining of Medline abstracts would be more effective. Therefore, we developed a novel algorithm (LAMA: Literature-Aided Meta-Analysis) to quantify the similarity between transcriptomics studies. We evaluated our algorithm on a large compendium of 102 microarray studies published in the field of muscle development and disease, and compared it to similarity measures based on gene overlap and over-representation of biological processes assigned by GO. Results: While the overlap in both genes and overrepresented GO-terms was poor, LAMA retrieved many more biologically meaningful links between studies, with substantially lower influence of technical factors. LAMA correctly grouped muscular dystrophy, regeneration and myositis studies, and linked patient and corresponding mouse model studies. LAMA also retrieves the connecting biological concepts. Among other new discoveries, we associated cullin proteins, a class of ubiquitinylation proteins, with genes down-regulated during muscle regeneration, whereas ubiquitinylation was previously reported to be activated during the inverse process: muscle atrophy. Conclusion: Our literature-based association analysis is capable of finding hidden common biological denominators in microarray studies, and circumvents the need for raw data analysis or curated gene annotation databases
The effect of botulinum toxin A in children with non-neurogenic therapy-refractory dysfunctional voiding â A systematic review
Introduction:Dysfunctional voiding (DV) is a habitual voiding disorder caused by involuntary contraction or non-relaxation of the external urethral sphincter (EUS) during voiding. This contraction causes high post-void residuals (PVR), urinary incontinence and urinary tract infections (UTIs). Various treatments for DV are available, but some children do not respond. Intersphincteric botulinum toxin-A (BTX-A) may be a possible treatment for therapy-refractory children with DV.Objective: The aim of this systematic review is to summarize the effects and safety of intersphincteric BTX-A as a treatment for therapy-refractory DV in children. Methods: A systematic search in Embase, MEDLINE, Cochrane, and Web of Science databases was performed. Studies reporting on the usage of intersphincteric BTX-A as a treatment for DV in children were included. Data on PVR, maximum flow rate (Qmax), repeat injections and complications were extracted. Results: From a total of 277 articles, five cohort studies were identified, reporting on 78 children with DV of whom 53 were female (68 %) and 25 were male (32 %). Sample sizes ranged from ten to twenty patients. Mean or median age at the time of intervention ranged from 8 to 10.5 years. Meta-analysis could not be performed due to lack of data. The narrative synthesis approach was therefore used to summarize the results. All studies showed significant decrease in PVR after BTX-A injection. Three studies showed a 33â69 % improvement on incontinence after BTX-A injection. Less UTIs were reported after treatment. A temporary increase in incontinence, UTIs and transitory numbness to the gluteus muscle were reported as side-effects. Conclusions: BTX-A could be a safe and effective treatment option for therapy-refractory DV in children by reducing PVR, UTIs and incontinence. Hereby, the synergistic effect of BTX-A and urotherapy should be emphasized in future management. Furthermore, this study identified gaps in current knowledge that are of interest for future research.</p
Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease
<p>Abstract</p> <p>Background</p> <p>Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.</p> <p>Results</p> <p>Before aggregation, up-regulation of gene expression predominated, while after aggregates became visible, down-regulation and up-regulation occurred to the same extent. After aggregates became visible there was a down-regulation of dopamine biosynthesis genes accompanied by down-regulation of dopamine levels in culture, indicating the utility of this model to identify functionally relevant pathways. Furthermore, genes of the anti-oxidant Nrf2-ARE pathway were up-regulated, possibly as a protective mechanism. In parallel, we discovered alterations in genes which may result in increased oxidative stress and damage.</p> <p>Conclusion</p> <p>Up-regulation of gene expression may be more important in HD pathology than previously appreciated. In addition, given the pathogenic impact of oxidative stress and neuroinflammation, the Nrf2-ARE signaling pathway constitutes a new attractive therapeutic target for HD.</p
Interspecies Translation of Disease Networks Increases Robustness and Predictive Accuracy
Gene regulatory networks give important insights into the mechanisms underlying physiology and pathophysiology. The derivation of gene regulatory networks from high-throughput expression data via machine learning strategies is problematic as the reliability of these models is often compromised by limited and highly variable samples, heterogeneity in transcript isoforms, noise, and other artifacts. Here, we develop a novel algorithm, dubbed Dandelion, in which we construct and train intraspecies Bayesian networks that are translated and assessed on independent test sets from other species in a reiterative procedure. The interspecies disease networks are subjected to multi-layers of analysis and evaluation, leading to the identification of the most consistent relationships within the network structure. In this study, we demonstrate the performance of our algorithms on datasets from animal models of oculopharyngeal muscular dystrophy (OPMD) and patient materials. We show that the interspecies network of genes coding for the proteasome provide highly accurate predictions on gene expression levels and disease phenotype. Moreover, the cross-species translation increases the stability and robustness of these networks. Unlike existing modeling approaches, our algorithms do not require assumptions on notoriously difficult one-to-one mapping of protein orthologues or alternative transcripts and can deal with missing data. We show that the identified key components of the OPMD disease network can be confirmed in an unseen and independent disease model. This study presents a state-of-the-art strategy in constructing interspecies disease networks that provide crucial information on regulatory relationships among genes, leading to better understanding of the disease molecular mechanisms
Coupling of the lattice and superlattice deformations and hysteresis in thermal expansion for the quasi one-dimensional conductor TaS
An original interferometer-based setup for measurements of length of
needle-like samples is developed, and thermal expansion of o-TaS crystals
is studied. Below the Peierls transition the temperature hysteresis of length
is observed, the width of the hysteresis loop being up to . The behavior of the loop is anomalous: the length changes so
that it is in front of its equilibrium value. The hysteresis loop couples with
that of conductivity. The sign and the value of the length hysteresis are
consistent with the strain dependence of the charge-density waves (CDW) wave
vector. With lowering temperature down to 100 K the CDW elastic modulus grows
achieving a value comparable with the lattice Young modulus. Our results could
be helpful in consideration of different systems with intrinsic
superstructures.Comment: 4 pages, 3 figures. Phys. Rev. Lett., accepted for publicatio
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