Characterization of microRNA expression profiles in normal human tissues

<p>Abstract</p> <p>Background</p> <p>Measuring the quantity of miRNAs in tissues of different physiological and pathological conditions is an important first step to investigate the functions of miRNAs. Matched samples from normal state can provide essential baseline references to analyze the variation of miRNA abundance.</p> <p>Results</p> <p>We provided expression data of 345 miRNAs in 40 normal human tissues, which identified universally expressed miRNAs, and several groups of miRNAs expressed exclusively or preferentially in certain tissue types. Many miRNAs with co-regulated expression patterns are located within the same genomic clusters, and candidate transcriptional factors that control the pattern of their expression may be identified by a comparative genomic strategy. Hierarchical clustering of normal tissues by their miRNA expression profiles basically followed the structure, anatomical locations, and physiological functions of the organs, suggesting that functions of a miRNA could be appreciated by linking to the biologies of the tissues in which it is uniquely expressed. Many predicted target genes of miRNAs that had specific reduced expression in brain and peripheral blood mononuclear cells are required for embryonic development of the nervous and hematopoietic systems based on database search.</p> <p>Conclusion</p> <p>We presented a global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures. We also described evidence from the <it>cis</it>-regulatory elements and the predicted target genes of miRNAs to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.</p

Comparison of die geometry for cold drawing of multi-rifled steel tubes

Multi-rifled tubes, i.e. tubes with multiple inner grooving are used in heat exchangers and boilers, providing favourable heat transfer conditions due to turbulent flow of cooling medium. Therefore, strict requirements are placed on the geometry of inner rifling. In production of such tubes, cold drawing with free-to-rotate rifled plug is the final drawing operation to achieve required dimensions. A Finite Element Method (FEM) based numerical model of the process was prepared in order to optimize the geometry of the die. The results of numerical simulations for two different die geometries show the difference in material flow and corresponding drawing force. The final dimensions of the tubes after drawing were compared with the customer`s requirements and a good agreement was found

Validation of results of two different reductions for precision seamless cold drawn tubes

This paper deals with the comparison of the seamless pulling process of precision seamless tubes using two different reductions from the viewpoint of geometrical stability using computerized tomography, from the point of view of mechanical properties, from the point of view of the surface temperature in the arrangement of the tribological tube-tool pair. Validation of the pipe drawing process also took place based on the finite element method in the simulation program DEFORM 3D. From the point of view of production rationalization, it is necessary to analyze stress and deformation states at different input dimensions for a particular final dimension for a given drawing method, in this case, a drawing whiteout plug method was used

Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial.

ObjectivesThe objective of this trial was to investigate the safety and preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil fumarate (TDF) versus placebo in preventing HIV infection in women.DesignThis was a phase 2, randomized, double-blind, placebo-controlled trial.SettingThe study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.ParticipantsWe enrolled 936 HIV-negative women at high risk of HIV infection into this study.InterventionParticipants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.Outcome measuresThe primary safety endpoints were grade 2 or higher serum creatinine elevations (&gt;2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations (&gt;170 U/l) for hepatic function, and grade 3 or 4 phosphorus abnormalities (&lt;1.5 mg/dl). The effectiveness endpoint was infection with HIV-1 or HIV-2.ResultsStudy participants contributed 428 person-years of laboratory testing to the primary safety analysis. No significant differences emerged between treatment groups in clinical or laboratory safety outcomes. Study participants contributed 476 person-years of HIV testing to the primary effectiveness analysis, during which time eight seroconversions occurred. Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years) and six in participants receiving placebo (2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03-1.93), which did not achieve statistical significance. Owing to premature closures of the Cameroon and Nigeria study sites, the planned person-years of follow-up and study power could not be achieved.ConclusionDaily oral use of TDF in HIV-uninfected women was not associated with increased clinical or laboratory adverse events. Effectiveness could not be conclusively evaluated because of the small number of HIV infections observed during the study

CFMC Digital Education Research

Through this project, our group was able to understand how to use market research as a tool for representing diverse perspectives. This is incredibly relevant as the business issue we investigated was how to digitally educate a collective/unified voice to a diverse group of end users. To achieve this, we included both qualitative and quantitative research in our project to get as rich and varied insights as possible, accounting for accessibility and ensuring people have multiple avenues to share. This guiding principle relates nicely to our group\u27s anti-racist values as we have made sure to value all perspectives while gathering research and commit to including input from all voices

The microRNA body map : dissecting microRNA function through integrative genomics

While a growing body of evidence implicates regulatory miRNA modules in various aspects of human disease and development, insights into specific miRNA function remain limited. Here, we present an innovative approach to elucidate tissue-specific miRNA functions that goes beyond miRNA target prediction and expression correlation. This approach is based on a multi-level integration of corresponding miRNA and mRNA gene expression levels, miRNA target prediction, transcription factor target prediction and mechanistic models of gene network regulation. Predicted miRNA functions were either validated experimentally or compared to published data. The predicted miRNA functions are accessible in the miRNA bodymap, an interactive online compendium and mining tool of high-dimensional newly generated and published miRNA expression profiles. The miRNA bodymap enables prioritization of candidate miRNAs based on their expression pattern or functional annotation across tissue or disease subgroup. The miRNA bodymap project provides users with a single one-stop data-mining solution and has great potential to become a community resource

Real-time quantification of microRNAs by stem–loop RT–PCR

A novel microRNA (miRNA) quantification method has been developed using stem–loop RT followed by TaqMan PCR analysis. Stem–loop RT primers are better than conventional ones in terms of RT efficiency and specificity. TaqMan miRNA assays are specific for mature miRNAs and discriminate among related miRNAs that differ by as little as one nucleotide. Furthermore, they are not affected by genomic DNA contamination. Precise quantification is achieved routinely with as little as 25 pg of total RNA for most miRNAs. In fact, the high sensitivity, specificity and precision of this method allows for direct analysis of a single cell without nucleic acid purification. Like standard TaqMan gene expression assays, TaqMan miRNA assays exhibit a dynamic range of seven orders of magnitude. Quantification of five miRNAs in seven mouse tissues showed variation from less than 10 to more than 30 000 copies per cell. This method enables fast, accurate and sensitive miRNA expression profiling and can identify and monitor potential biomarkers specific to tissues or diseases. Stem–loop RT–PCR can be used for the quantification of other small RNA molecules such as short interfering RNAs (siRNAs). Furthermore, the concept of stem–loop RT primer design could be applied in small RNA cloning and multiplex assays for better specificity and efficiency

Multidrug-resistant Tuberculosis in Military Recruits

We conducted a tuberculosis contact investigation for a female military recruit with an unreported history of multidrug-resistant tuberculosis (MDRTB) and subsequent recurrence. Pertinent issues included identification of likely contacts from separate training phases, uncertainty on latent MDRTB infection treatment regimens and side effects, and subsequent dispersal of the contacts after exposure

In Global Health Research, Is It Legitimate To Stop Clinical Trials Early on Account of Their Opportunity Costs?

This debate examines the ethics of reallocating resources invested in existing trials of older products into new trials of more scientifically advanced products

Bioterrorism-Related Anthrax Surveillance, Connecticut, September–December, 2001

On November 19, 2001, a case of inhalational anthrax was identified in a 94-year-old Connecticut woman, who later died. We conducted intensive surveillance for additional anthrax cases, which included collecting data from hospitals, emergency departments, private practitioners, death certificates, postal facilities, veterinarians, and the state medical examiner. No additional cases of anthrax were identified. The absence of additional anthrax cases argued against an intentional environmental release of Bacillus anthracis in Connecticut and suggested that, if the source of anthrax had been cross-contaminated mail, the risk for anthrax in this setting was very low. This surveillance system provides a model that can be adapted for use in similar emergency settings