Abstract:We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5-5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have investigated the stability of a mutant c-MYC i-motif in solutions containing a molecular crowding agent. The crowded nuclear environment was modeled by the addition of up to 40% w/w polyethylene glycols having molecular weights up to 12,000 g/mol. CD and DSC were used to establish the presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4 to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH values as high as 6.7 in crowded solutions. Generic dielectric constant effects, e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or the formation of non-specific PEG/DNA complexes appear to contribute insignificantly to i-motif stabilization. Molecular crowding, largely an excluded volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol, appears to be responsible for stabilizing the more compact i-motif over the random coil at higher pH values.

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BackgroundTo evaluate the feasibility of using radiomics with precontrast magnetic resonance imaging for classifying hepatocellular carcinoma (HCC) and hepatic haemangioma (HH).MethodsThis study enrolled 369 consecutive patients with 446 lesions (a total of 222 HCCs and 224 HHs). A training set was constituted by randomly selecting 80% of the samples and the remaining samples were used to test. On magnetic resonance (MR) images of HCC and HH obtained with in-phase, out-phase, T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) sequences, we outlined the target lesions and extracted 1029 radiomics features, which were classified as first-, second-, higher-order statistics and shape features. Then, the variance threshold, select k best, and least absolute shrinkage and selection operator algorithms were explored for dimensionality reduction of the features. We used four classifiers (decision tree, random forest, K nearest neighbours, and logistic regression) to identify HCC and HH on the basis of radiomics features. Two abdominal radiologists also performed the conventional qualitative analysis for classification of HCC and HH. Diagnostic performances of radiomics and radiologists were evaluated by receiver operating characteristic (ROC) analysis.ResultsValuable radiomics features for building a radiomics signature were extracted from in-phase (n = 22), out-phase (n = 24), T2WI (n = 34) and DWI (n = 24) sequences. In comparison, the logistic regression classifier showed better predictive ability by combining four sequences. In the training set, the area under the ROC curve (AUC) was 0.86 (sensitivity: 0.76; specificity: 0.78), and in the testing set, the AUC was 0.89 (sensitivity: 0.822; specificity: 0.714). The diagnostic performance for the optimal radiomics-based combined model was significantly higher than that for the less experienced radiologist (2-years experience) (AUC = 0.702, p < 0.05), and had no statistic difference with the experienced radiologist (10-years experience) (AUC = 0.908, p>0.05).ConclusionsWe developed and validated a radiomics signature as an adjunct tool to distinguish HCC and HH by combining in-phase, out-phase, T2W, and DW MR images, which outperformed the less experienced radiologist (2-years experience), and was nearly equal to the experienced radiologist (10-years experience).

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The cancellation of echoes is a vital component of telephony networks. In some cases the echo response that must be identified by the echo canceller is sparse, as for example when telephony traffic is routed over networks with unknown delay such as packet-switched networks. The sparse nature of such a response causes standard adaptive algorithms including normalized LMS to perform poorly. This paper begins by providing a review of techniques that aim to give improved echo cancellation performance when the echo response is sparse. In addition, adaptive filters can also be designed to exploit sparseness in the input signal by using partial update procedures. This concept is discussed and the MMax procedure is reviewed. We proceed to present a new high performance sparse adaptive algorithm and provide comparative echo cancellation results to show the relative performance of the existing and new algorithms. Finally, an efficient low cost implementation of our new algorithm using partial update adaptation is presented and evaluated. This algorithm exploits both sparseness of the echo response and also sparseness of the input signal in order to achieve high performance without high computational cost. r

Lacking of treatment methods for the patients with triple negative breast cancer (TNBC) underscores the pivotal needs to further understand its biology as well as to find better biomarkers and develop novel therapeutic strategies. Increasing evidences support that aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis and may serve as biomarkers for diagnostic and prognostic purposes of various cancers. In current study, we found that miR-455-3p and miR-196a-5p were intensively overexpressed in TNBC compared with the hormone receptor (HR) positive breast cancer whereas miR-425-5p was down-regulated by miRNA microarray analysis. qRT-PCR analysis confirmed that the expression of miR-455-3p in TNBC cell lines MDA-MB-231 and MDA-MB-468 was higher than that in HR positive breast cancer cell line MCF-7(p<0.01). Functional experiments in vitro showed that miR-455-3p enhanced cell proliferative, invasive and migrational abilities in TNBC cell lines. miRNA targets prediction showed SMAD2, LTBR and etoposide induced 2.4 (EI24) were potential target genes of miR-455-3p, and then it was confirmed by qRT-PCR assay. Dual luciferase reporter assay showed the specific binding of miR-455-3p to 3′ UTR of EI24 in TNBC. Then we found miR-455-3p inhibited the EI24 expression at the levels of mRNA and protein. Through small interfering RNA (siRNA) targeting EI24 gene, there were strengthened capabilities of invasion and migration of TNBC cells, and increased expression of EI24 had the inverse effects. In conclusion, the data suggest that miRNA455-3p promotes invasion and migration by targeting tumor suppressor EI24 and might be a potential prognostic biomarker and therapeutic target in TNBC.