A System for Accessible Artificial Intelligence

While artificial intelligence (AI) has become widespread, many commercial AI systems are not yet accessible to individual researchers nor the general public due to the deep knowledge of the systems required to use them. We believe that AI has matured to the point where it should be an accessible technology for everyone. We present an ongoing project whose ultimate goal is to deliver an open source, user-friendly AI system that is specialized for machine learning analysis of complex data in the biomedical and health care domains. We discuss how genetic programming can aid in this endeavor, and highlight specific examples where genetic programming has automated machine learning analyses in previous projects.Comment: 14 pages, 5 figures, submitted to Genetic Programming Theory and Practice 2017 worksho

Acute Drug Treatment in the Early C. elegans Embryo

Genetic and genome-wide RNAi approaches available in C. elegans, combined with tools for visualizing subcellular events with high-resolution, have led to increasing adoption of the early C. elegans embryo as a model for mechanistic and functional genomic analysis of cellular processes. However, a limitation of this system has been the impermeability of the embryo eggshell, which has prevented the routine use of small molecule inhibitors. Here, we present a method to permeabilize and immobilize embryos for acute inhibitor treatment in conjunction with live imaging. To identify a means to permeabilize the eggshell, we used a dye uptake assay to screen a set of 310 candidate genes defined by a combination of bioinformatic criteria. This screen identified 20 genes whose inhibition resulted in >75% eggshell permeability, and 3 that permeabilized embryos with minimal deleterious effects on embryo production and early embryonic development. To mount permeabilized embryos for acute drug addition in conjunction with live imaging, we combined optimized inhibition of one of these genes with the use of a microfabricated chamber that we designed. We demonstrate that these two developments enable the temporally controlled introduction of inhibitors for mechanistic studies. This method should also open new avenues of investigation by allowing profiling and specificity-testing of inhibitors through comparison with genome-wide phenotypic datasets

Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

<p>Abstract</p> <p>Background</p> <p>Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.</p> <p>Methods</p> <p>We performed a retrospective analysis of laboratory orders and results at a national referral laboratory to gain insight into physicians' ordering practices, specifically comparing them against the ordering practices recommended by a 2002 College of American Pathologists (CAP) consensus conference on thrombophilia testing. Measurements included absolute and relative ordering volumes and positivity rates from approximately 200,000 thrombophilia tests performed from September 2005 through August 2006 at a national reference laboratory. Quality control data were used to estimate the proportion of samples that may have been affected by anticoagulant therapy. A sample of ordering laboratories was surveyed in order to assess potential measurement bias.</p> <p>Results</p> <p>Total antigen assays for protein C, protein S and antithrombin were ordered almost as frequently as functional assays for these analytes. The DNA test for factor V Leiden was ordered much more often than the corresponding functional assay. In addition, relative positivity rates coupled with elevations in prothrombin time (PT) in many of these patients suggest that these tests are often ordered in the setting of oral anticoagulant therapy.</p> <p>Conclusion</p> <p>In this real-world setting, testing for inherited thrombophilia is frequently at odds with the recommendations of the CAP consensus conference. There is a need for wider dissemination of concise thrombophilia testing guidelines.</p

Pneumatosis intestinalis versus pseudo-pneumatosis: review of CT findings and differentiation

Pneumatosis intestinalis is defined as the presence of gas within the wall of the gastrointestinal tract. Originally described on plain abdominal radiographs, it is an imaging sign rather than a specific diagnosis and it is associated with both benign and life-threatening clinical conditions. The most common life-threatening cause of pneumatosis intestinalis is bowel ischaemia. Computed tomography (CT) is usually requested to detect underlying disease. The presence of pneumatosis intestinalis often leads physicians to make a diagnosis of serious disease. However, an erroneous diagnosis of pneumatosis intestinalis may be made (i.e. pseudo-pneumatosis) when intraluminal beads of gas are trapped within or between faeces and adjacent mucosal folds. The purpose of this pictorial essay is to review and describe the CT imaging findings of pneumatosis and pseudo-pneumatosis intestinalis and to discuss key discriminatory imaging features

Test-retest repeatability of child's respiratory symptoms and perceived indoor air quality - comparing self-and parent-administered questionnaires

Background: Questionnaires can be used to assess perceived indoor air quality and symptoms in schools. Questionnaires for primary school aged children have traditionally been parent-administered, but self-administered questionnaires would be easier to administer and may yield as good, if not better, information. Our aim was to compare the repeatability of self- and parent-administered indoor air questionnaires designed for primary school aged pupils. Methods: Indoor air questionnaire with questions on child's symptoms and perceived indoor air quality in schools was sent to parents of pupils aged 7-12 years in two schools and again after two weeks. Slightly modified version of the questionnaire was administered to pupils aged 9-12 years in another two schools and repeated after a week. 351 (52%) parents and 319 pupils (86%) answered both the first and the second questionnaire. Test-retest repeatability was assessed with intra-class correlation (ICC) and Cohen's kappa coefficients (k). Results: Test-retest repeatability was generally between 0.4-0.7 (ICC; k) in both self-and parent-administered questionnaire. In majority of the questions on symptoms and perceived indoor air quality test-retest repeatability was at the same level or slightly better in self-administered compared to parent-administered questionnaire. Agreement of self-and parent administered questionnaires was generally <0.4 (ICC; k) in reported symptoms and 0.4-0.6 (ICC; k) in perceived indoor air quality. Conclusions: Children aged 9-12 years can give as, or even more, repeatable information about their respiratory symptoms and perceived indoor air quality than their parents. Therefore, it may be possible to use self-administered questionnaires in future studies also with children.Peer reviewe

Transcriptome Fingerprinting Analysis: An Approach to Explore Gene Expression Patterns in Marine Microbial Communities

Microbial transcriptomics are providing new insights into the functional processes of microbial communities. However, analysis of each sample is still expensive and time consuming. A rapid and low cost method that would allow the identification of the most interesting samples for posterior in-depth metatranscriptomics analysis would be extremely useful. Here we present Transcriptome Fingerprinting Analysis (TFA) as an approach to fulfill this objective in microbial ecology studies. We have adapted the differential display technique for mRNA fingerprinting based on the PCR amplification of expressed transcripts to interrogate natural microbial eukaryotic communities. Unlike other techniques, TFA does not require prior knowledge of the mRNA sequences to be detected. We have used a set of arbitrary primers coupled with a fluorescence labeled primer targeting the poly(A) tail of the eukaryotic mRNA, with further detection of the resulting labeled cDNA products in an automated genetic analyzer. The output represented by electropherogram peak patterns allowed the comparison of a set of genes expressed at the time of sampling. TFA has been optimized by testing the sensitivity of the method for different initial RNA amounts, and the repeatability of the gene expression patterns with increasing time after sampling both with cultures and environmental samples. Results show that TFA is a promising approach to explore the dynamics of gene expression patterns in microbial communities

K-Ras Mediated Murine Epidermal Tumorigenesis Is Dependent upon and Associated with Elevated Rac1 Activity

A common goal for potential cancer therapies is the identification of differences in protein expression or activity that would allow for the selective targeting of tumor vs. normal cells. The Ras proto-oncogene family (K-Ras, H-Ras and N-Ras) are amongst the most frequently mutated genes in human cancers. As a result, there has been substantial effort dedicated to determining which pathways are activated by Ras signaling and, more importantly, which of these contribute to cancer. Although the most widely studied Ras-regulated signaling pathway is the Raf/mitogen-activated protein kinase cascade, previous research in model systems has revealed that the Rac1 GTP-binding protein is also required for Ras-induced biological responses. However, what have been lacking are rigorous in vivo Rac1 target validation data and a clear demonstration that in Ras-driven hyperplastic lesions, Rac1 activity is increased. Using a combination of genetically-modified mouse models that allow for the tissue-selective activation or deletion of signaling molecules and an activation-state sensitive Rac1 antibody that detects GTP-bound Rac1, we found that Rac1 contributes to K-Ras induced epidermal papilloma initiation and growth and that Rac1 activity is elevated by oncogenic K-Ras in vivo. Previously, it was not practical to assess Rac1 activation status in the most commonly used format for clinical tumor specimens, formalin-fixed paraffin embedded (FFPE) tissues samples. However, this study clearly demonstrates that Rac1 is essential for K-Ras driven epithelial cell hyperproliferation and that Rac1 activity is elevated in tissues expressing mutant oncogenic K-Ras, while also characterizing the activation-state specific Rac1-GTP antibody as a probe to examine Rac1 activation status in FFPE samples. Our findings will facilitate further research on the status of Rac1 activity in human tumors and will help to define the tumor types of the patient population that could potentially benefit from therapies targeting Rac activation or downstream effector signaling pathways

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Histoplasmosis infection in patients with rheumatoid arthritis, 1998-2009

<p>Abstract</p> <p>Background</p> <p>Patients with rheumatic diseases including rheumatoid arthritis (RA) are at increased risk for infections related to both the disease and its treatments. These include uncommonly reported infections due to histoplasmosis.</p> <p>Methods</p> <p>Medical record review of all patients with a diagnosis of RA who developed new histoplasmosis infection in an endemic region between Jan 1, 1998 and Jan 30, 2009 and who were seen at Mayo Clinic in Rochester, Minnesota was performed.</p> <p>Results</p> <p>Histoplasmosis was diagnosed in 26 patients. Most patients were on combination therapies; 15 were on anti-tumor necrosis factor (anti-TNF) agents, 15 on corticosteroids and 16 on methotrexate. Most received more than 6 months of itraconazole and/or amphotericin treatment. Two patients died of causes unrelated to histoplasmosis. Anti-TNF treatment was restarted in 4/15 patients, with recurrence of histoplasmosis in one.</p> <p>Conclusions</p> <p>In this largest single center series of patients with RA and histoplasmosis in the era of immunomodulatory therapy, we found that most patients had longstanding disease and were on multiple immunomodulatory agents. Most cases were pulmonary; typical signs and symptoms of disease were frequently lacking.</p