Make mine a quadruple: Strengthening the security of graphical one-time PIN authentication

Secure and reliable authentication is an essential prerequisite for many online systems, yet achieving this in a way which is acceptable to customers remains a challenge. GrIDsure, a one-time PIN scheme using random grids and personal patterns, has been proposed as a way to overcome some of these challenges. We present an analytical study which demonstrates that GrIDsure in its current form is vulnerable to interception. To strengthen the scheme, we propose a way to fortify GrIDsure against Man-in-the-Middle attacks through (i) an additional secret transmitted out-of-band and (ii) multiple patterns. Since the need to recall multiple patterns increases user workload, we evaluated user performance with multiple captures with 26 participants making 15 authentication attempts each over a 3-week period. In contrast with other research into the use of multiple graphical passwords, we find no significant difference in the usability of GrIDsure with single and with multiple patterns. © 2011 IEEE

Revealing dendritic pattern formation in Ni, Fe and Co alloys using synchrotron tomography

The microstructural patterns formed during liquid to solid phase transformations control the properties of a wide range of materials. We developed a novel methodology that allows in situ quantification of the microstructures formed during solidification of high temperature advanced alloys. The patterns formed are captured in 4D (3D plus time) using a methodology which exploits three separate advances: a bespoke high temperature environment cell; the development of high X-ray contrast alloys; and a novel environmental encapsulation system. This methodology is demonstrated on Ni, Fe, and Co advanced alloy systems, revealing dendritic pattern formation. We present detailed quantification of microstructural pattern evolution in a novel high attenuation contrast Co-Hf alloy, including microstructural patterning and dendrite tip velocity. The images are quantified to provide 4D experimental data of growth and coarsening mechanisms in Co alloys, which are used for a range of applications from energy to aerospace

Correlative multi-scale imaging of shales: A review and future perspectives

As the fastest growing energy sector globally, shale and shale reservoirs have attracted the attention of both industry and scholars. However, the strong heterogeneity at different scales and the extremely fine-grained nature of shales makes macroscopic and microscopic characterization highly challenging. Recent advances in imaging techniques have provided many novel characterization opportunities of shale components and microstructures at multiple scales. Correlative imaging, where multiple techniques are combined, is playing an increasingly important role in the imaging and quantification of shale microstructures (e.g. one can combine optical microscopy, scanning electron microscopy/transmission electron microscopy and X-ray radiography in 2D, or X-ray computed tomography and electron microscopy in 3D). Combined utilization of these techniques can characterize the heterogeneity of shale microstructures over a large range of scales, from macroscale to nanoscale (c. 100-10-9 m). Other chemical and physical measurements can be correlated to imaging techniques to provide complementary information for minerals, organic matter and pores. These imaging techniques and subsequent quantification methods are critically reviewed to provide an overview of the correlative imaging workflow. Applications of the above techniques for imaging particular features in different shales are demonstrated, and key limitations and benefits summarized. Current challenges and future perspectives in shale imaging techniques and their applications are discussed

On the kinematics of the Local cosmic void

We collected the existing data on the distances and radial velocities of galaxies around the Local Void in the Aquila/Hercules to examine the peculiar velocity field induced by its underdensity. A sample of 1056 galaxies with distances measured from the Tip of the Red Giant Branch, the Cepheid luminosity, the SNIa luminosity, the surface brightness fluctuation method, and the Tully-Fisher relation has been used for this purpose. The amplitude of outflow is found to be ~300 km/s. The galaxies located within the void produce the mean intra-void number density about 1/5 of the mean external number density of galaxies. The void's population has a lower luminosity and a later morphological type with the medians: M_B = -15.7^m and T = 8 (Sdm), respectively.Comment: Version 1. 14 pages, 8 figures, 2 tables. Accepted to Astrophysics, Volume 54, Issue

Synchrotron tomographic quantification of strain and fracture during simulated thermal maturation of an organic-rich shale, UK Kimmeridge Clay

Analyzing the development of fracture networks in shale is important to understand both hydrocarbon migration pathways within and from source rocks and the effectiveness of hydraulic stimulation upon shale reservoirs. Here we use time‐resolved synchrotron X‐ray tomography to quantify in four dimensions (3‐D plus time) the development of fractures during the accelerated maturation of an organic‐rich mudstone (the UK Kimmeridge Clay), with the aim of determining the nature and timing of crack initiation. Electron microscopy (EM, both scanning backscattered and energy dispersive) was used to correlatively characterize the microstructure of the sample preheating and postheating. The tomographic data were analyzed by using digital volume correlation (DVC) to measure the three‐dimensional displacements between subsequent time/heating steps allowing the strain fields surrounding each crack to be calculated, enabling crack opening modes to be determined. Quantification of the strain eigenvectors just before crack propagation suggests that the main mode driving crack initiation is the opening displacement perpendicular to the bedding, mode I. Further, detailed investigation of the DVC measured strain evolution revealed the complex interaction of the laminar clay matrix and the maximum principal strain on incipient crack nucleation. Full field DVC also allowed accurate calculation of the coefficients of thermal expansion (8 × 10−5/°C perpendicular and 6.2 × 10−5/°C parallel to the bedding plane). These results demonstrate how correlative imaging (using synchrotron tomography, DVC, and EM) can be used to elucidate the influence of shale microstructure on its anisotropic mechanical behavior

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis

Rationale, design and methodology for Intraventricular Pressure Gradients Study: a novel approach for ventricular filling assessment in normal and falling hearts

<p>Abstract</p> <p>Background</p> <p>Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. Although, systolic gradients have also been observed, data are lacking on their magnitude and modulation during cardiac dysfunction. Furthermore, we know that segmental dysfunction interferes with the normal sequence of regional contraction and might be expected to alter the physiological intraventricular pressure gradients. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis.</p> <p>Methods/Design</p> <p><it>Animal Studies: </it>Six rabbits will be completely instrumented to measuring apex to outflow-tract pressure gradient and apical and basal myocardial segments lengthening changes at basal, afterloaded and ischemic conditions. Afterload increase will be performed by abruptly narrowing or occluding the ascending aorta during the diastole and myocardial ischemia will be induced by left coronary artery ligation, after the first diagonal branch.</p> <p><it>Patient Studies: </it>Patients between 65-80 years old (n = 12), both genders, with severe aortic stenosis referred for aortic valve replacement will be selected as eligible subjects. A high-fidelity pressure-volume catheter will be positioned through the ascending aorta across the aortic valve to measure apical and outflow-tract pressure before and after aortic valve replacement with a bioprosthesis. Peak and average intraventricular pressure gradients will be recorded as apical minus outflow-tract pressure and calculated during all diastolic and systolic phases of cardiac cycle.</p> <p>Discussion</p> <p>We expect to validate the application of our method to obtain intraventricular pressure gradients in animals and patients and to promote a methodology to better understand the ventricular relaxation and filling and their correlation with systolic function.</p

HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of <it>HNF1A </it>have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.</p> <p>Methods</p> <p>We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.</p> <p>Results</p> <p>Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular <it>SNAIL </it>and <it>SLUG</it>. We also found an overexpression of TGFβ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFβ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFβ1 expression by HNF1α.</p> <p>Conclusion</p> <p>Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.</p

Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>CD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers. Our work evaluates the mechanism involved in confluence-dependent CD26 expression in colon cancer.</p> <p>Methods</p> <p>Colon adenocarcinoma cells were grown to confluence, and expression of CD26 and transcription factors implicated in its regulation was confirmed by immunofluorescence and Western blotting. Real-time PCR was also performed to evaluate CD26 upregulation at the transcriptional level. The influence of c-Myc on CD26 expression during different growth conditions was further evaluated following transient transfection of a c-Myc-expressing plasmid and a c-Myc specific siRNA.</p> <p>Results</p> <p>We found that the colon cancer cell lines HCT-116 and HCT-15 exhibited a confluence-dependent increase in CD26 mRNA and protein, associated with decreased expression of c-Myc, increased USF-1 and Cdx 2 levels, and unchanged HNF-1α expression. Meanwhile, ectopic expression of c-Myc in both cell lines led to decreased CD26 expression. In contrast, transfection of a siRNA targeted to Cdx2 resulted in decreased CD26 level. Importantly, culturing of cells in serum-depleted media, but not acidic conditions, upregulated CD26. While HIF-1α level also increased when cells were cultured in serum-depleted media, its expression was required but not sufficient for CD26 upregulation.</p> <p>Conclusions</p> <p>CD26 mRNA and protein levels increase in a confluence-dependent manner in colon carcinoma cell lines, with c-Myc acting as a repressor and Cdx2 acting as an enhancer of CD26 expression. The enhanced expression of CD26 in serum-depleted media and a requirement for HIF-1α suggest a role for nutrients or growth factors in the regulation of CD26 protein expression.</p