Modeling Equilibrium of microRNA Expression

MicroRNAs are a class of non-coding RNAs and the dysregulated expression of these short RNA molecules was frequently observed in cancer cells. The steady state level of microRNA concentration may differentiate the biological function of the cells between normal and impaired. To understand the steady state or equilibrium of microRNAs, their interactions with transcription factors and target genes need to be explored and visualized through prediction and network analysis algorithms. This article discusses the application of mathematical model for simulating the dynamics of network feedback loop so as to decipher the mechanism of microRNA regulation

Circulating Plasma MicroRNAs As Diagnostic Markers for NSCLC

Lung cancer is the most common cause of cancer deaths all over the world, in which non-small cell lung cancer (NSCLC) accounts for ~85% of cases. It is well known that microRNAs (miRNAs) play a critical role in various cellular processes, mediating post-transcriptional silencing either by mRNA degradation through binding the 3' UTR of target mRNA or by translational inhibition of the protein. In the past decade, miRNAs have also been increasingly identified in biological fluids such as human serum or plasma known as circulating or cell-free miRNAs, and may function as non-invasive diagnostic markers for various cancer types including NSCLC. Circulating tumor cells (CTCs) are those cells that are shed from solid tumors and then migrate into the circulation. However, reports concerning the roles of CTCs are quite rare, which may be attributed to the difficulties in the enrichment and detection of CTCs in the circulation. Although, there have been reassuring advances in identifying circulating miRNA-panels, which are assumed to be of diagnostic value in NSCLC early stage, some issues remain concerning the reliability of using miRNA panels as a diagnostic tool for NSCLC. In the current review, we are aiming at providing insights into the miRNAs biology, the mechanisms of miRNAs release into the bloodstream, cell-free miRNAs as the diagnostic markers for NSCLC and the current limitations of CTCs as diagnostic markers in NSCLC.Department of Health Technology and Informatic

Matching Reviewers to Customers: The Role of Demographics and Preferences in Hotel Online Booking

Travelers can easily refer to online reviews as a source of advice before booking a hotel; however, online reviews are not structured which make gathering useful information uneasy. What if online review sites can prioritize and direct the reviews that are most relevant to the customers and save them a lot of time? The value and usefulness of reviews are affected by the reviewers’ background. This study investigated whether customers tend to value the reviews written by similar people more than those written by dissimilar people. The first experiment showed that positive reviews increased consumers’ intention to book a hotel, negative reviews decreased bookings, and consumers were more affected by the reviews written by similar people. When demographics about reviewers are not available, customers will focus on other traits of the reviewer, such as preferences. The second experiment added shared preference between consumers and reviewers as another basis of similarity. Customers relied on reviewers’ preferences a clue of similarity when demographic similarity was not presented, and vice versa. Online reviews offer a good chance for managers to know their customers. Online review sites should use this information to form better strategies. The researchers showed that more relevant reviews can be displayed to customers by matching people’s demographics or preferences

Implications of MicroRNAs in the treatment of gefitinib-resistant non-small cell lung cancer

2015-2016 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Gene network exploration of crosstalk between apoptosis and autophagy in chronic myelogenous leukemia

Copyright © 2015 Fengfeng Wang et al. Background. Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear. Results. Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks. Conclusion. The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.Link_to_subscribed_fulltex

Acceleressence: Dark Energy from a Phase Transition at the Seesaw Scale

Simple models are constructed for "acceleressence" dark energy: the latent heat of a phase transition occurring in a hidden sector governed by the seesaw mass scale v^2/M_Pl, where v is the electroweak scale and M_Pl the gravitational mass scale. In our models, the seesaw scale is stabilized by supersymmetry, implying that the LHC must discover superpartners with a spectrum that reflects a low scale of fundamental supersymmetry breaking. Newtonian gravity may be modified by effects arising from the exchange of fields in the acceleressence sector whose Compton wavelengths are typically of order the millimeter scale. There are two classes of models. In the first class the universe is presently in a metastable vacuum and will continue to inflate until tunneling processes eventually induce a first order transition. In the simplest such model, the range of the new force is bounded to be larger than 25 microns in the absence of fine-tuning of parameters, and for couplings of order unity it is expected to be \approx 100 microns. In the second class of models thermal effects maintain the present vacuum energy of the universe, but on further cooling, the universe will "soon" smoothly relax to a matter dominated era. In this case, the range of the new force is also expected to be of order the millimeter scale or larger, although its strength is uncertain. A firm prediction of this class of models is the existence of additional energy density in radiation at the eV era, which can potentially be probed in precision measurements of the cosmic microwave background. An interesting possibility is that the transition towards a matter dominated era has occurred in the very recent past, with the consequence that the universe is currently decelerating.Comment: 10 pages, references adde

A particle swarm optimization-based algorithm for finding gapped motifs

<p>Abstract</p> <p>Background</p> <p>Identifying approximately repeated patterns, or motifs, in DNA sequences from a set of co-regulated genes is an important step towards deciphering the complex gene regulatory networks and understanding gene functions.</p> <p>Results</p> <p>In this work, we develop a novel motif finding algorithm (PSO+) using a population-based stochastic optimization technique called Particle Swarm Optimization (PSO), which has been shown to be effective in optimizing difficult multidimensional problems in continuous domains. We propose a modification of the standard PSO algorithm to handle discrete values, such as characters in DNA sequences. The algorithm provides several features. First, we use both consensus and position-specific weight matrix representations in our algorithm, taking advantage of the efficiency of the former and the accuracy of the latter. Furthermore, many real motifs contain gaps, but the existing methods usually ignore them or assume a user know their exact locations and lengths, which is usually impractical for real applications. In comparison, our method models gaps explicitly, and provides an easy solution to find gapped motifs without any detailed knowledge of gaps. Our method allows the presence of input sequences containing zero or multiple binding sites.</p> <p>Conclusion</p> <p>Experimental results on synthetic challenge problems as well as real biological sequences show that our method is both more efficient and more accurate than several existing algorithms, especially when gaps are present in the motifs.</p

Manufacturing Epidemics: The Role of Global Producers in Increased Consumption of Unhealthy Commodities Including Processed Foods, Alcohol, and Tobacco

In an article that forms part of the PLoS Medicine series on Big Food, David Stuckler and colleagues report that unhealthy packaged foods are being consumed rapidly in low- and middle-income countries, consistent with rapid expansion of multinational food companies into emerging markets and fueling obesity and chronic disease epidemics

Radiation dose reduction at a price: the effectiveness of a male gonadal shield during helical CT scans

BACKGROUND: It is estimated that 60 million computed tomography (CT) scans were performed during 2006, with approximately 11% of those performed on children age 0–15 years. Various types of gonadal shielding have been evaluated for reducing exposure to the gonads. The purpose of this study was to quantify the radiation dose reduction to the gonads and its effect on image quality when a wrap-around male pediatric gonad shield was used during CT scanning. This information is obtained to assist the attending radiologist in the decision to utilize such male gonadal shields in pediatric imaging practice. METHODS: The dose reduction to the gonads was measured for both direct radiation and for indirect scattered radiation from the abdomen. A 6 cm(3 )ion chamber (Model 10X5-6, Radcal Corporation, Monrovia, CA) was placed on a Humanoid real bone pelvic phantom at a position of the male gonads. When exposure measurements with shielding were made, a 1 mm lead wrap-around gonadal shield was placed around the ion chamber sensitive volume. RESULTS: The use of the shields reduced scatter dose to the gonads by a factor of about 2 with no appreciable loss of image quality. The shields reduced the direct beam dose by a factor of about 35 at the expense of extremely poor CT image quality due to severe streak artifacts. CONCLUSION: Images in the direct exposure case are not useful due to these severe artifacts and the difficulties in positioning these shields on patients in the scatter exposure case may not be warranted by the small absolute reduction in scatter dose unless it is expected that the patient will be subjected to numerous future CT scans

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD