Perspective of understanding for Children’s Privacy and Security

The thirteen years of age requirement to open any social network account does not guarantee that children under this age would not have access to social networks such as Facebook, Snapchat, Instagram, or YouTube just to mention some. The reason for this is that children want to be a part of this technological revolution, and create these accounts by lying about their age, or are aid by their parents without realizing the consequences this action might bring. While these social networks disclose that they delete information belonging to children under 13 from their databases as soon as they are aware of it, it is questionable if they are doing enough to protect children’s privacy , and if they should be liable for any incident related to this issue since such is widely known, but apparently neglected. Unfortunately, by social network administrators not reinforcing the age requirement policy, and launching features that makes its user’s personal information available to third parties, are indirectly exposing children with fraudulent accounts at risk of being victims of more serious ethical and social issues such as cyber bulling, and sex crimes. While it is determined that social network has little control over this issue, all which is left to do, is to provide parents with education and control of their children’s social network activity interaction to protect their privacy and keep them safe

Synthesis and characterization of photoaffinity labelling reagents towards the Hsp90 C-terminal domain

Glucosyl-novobiocin-based diazirine photoaffinity labelling reagents (PALs) were designed and synthesized to probe the Hsp90 C-terminal domain unknown binding pocket and the structure-activity relationship. Five PALs were successfully synthesized from novobiocin in six consecutive steps employing phase transfer catalytic glycosylation. Reactions were monitored and guided by analytical LC/MS which led to different strategies of adding either a PAL precursor or a sugar moiety first. The structures and bonding linkages of these compounds were characterised by various 2D-NMR spectroscopy and MS techniques. Synthetic techniques provide powerful probes for unknown protein binding pockets

A chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasma

Warfarin is an oral anticoagulant that requires frequent therapeutic drug monitoring due to a narrow therapeutic window, considerable interindividual variability in drug response, and susceptibility to drug-drug and drug-diet interactions. Enantiomeric separation and quantification of warfarin enantiomers and clinically important major hydroxylation metabolites are essential for drug interaction studies and phenotypic characterization of CYP2C9 and CYP3A4, the major Cytochrome P450 (CYP) enzymes involved in warfarin metabolism. Here, we describe the development and validation of a chiral high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based quantification of R-warfarin, S-warfarin, S-7-hydroxywarfarin (the major CYP2C9metabolite) and (9R; 10S)-10-hydroxywarfarin (the CYP3A4 metabolite) in human plasma. Simple protein precipitation-based extraction showed good recovery of analytes (82.9 - 96.9%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The lower limits of detection were 0.25nM (or ~0.08 ng/ml) for the warfarin enantiomers and 0.1nM (or ~0.04 ng/mL) for S-7-hydroxywarfarinand (9R; 10S)-10-hydroxywarfarin using only 50μL plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving warfarin

SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors

SHIP2 (Src homology 2 domain-containing inositol 5 '-phosphatase 2) belongs to the family of 5 '-phosphatases. It regulates the phosphoinositide 3-kinase (PI3K)-mediated insulin signalling cascade by dephosphorylating the 5 '-position of PtdIns(3,4,5)P3 to generate PtdIns(3,4)P2, suppressing the activity of the pathway. SHIP2 mouse models and genetic studies in human propose that increased expression or activity of SHIP2 contributes to the pathogenesis of the metabolic syndrome, hypertension and type 2 diabetes. This has raised great interest to identify SHIP2 inhibitors that could be used to design new treatments for metabolic diseases. This review summarizes the central mechanisms associated with the development of diabetic kidney disease, including the role of insulin resistance, and then moves on to describe the function of SHIP2 as a regulator of metabolism in mouse models. Finally, the identification of SHIP2 inhibitors and their effects on metabolic processes in vitro and in vivo are outlined. One of the newly identified SHIP2 inhibitors is metformin, the first-line medication prescribed to patients with type 2 diabetes, further boosting the attraction of SHIP2 as a treatment target to ameliorate metabolic disorders.Peer reviewe

In Situ SiRNA Assembly in Living Cells for Gene Therapy with MicroRNA Triggered Cascade Reactions Templated by Nucleic Acids

The in situ generation of siRNAs in living cells can greatly enhance the specificity and efficiency of gene therapy. Inspired by the natural molecular machines that organize different compartments sequentially in a limited space to facilitate cellular process, this work constructs a DNA nanomachine (DNM) by alternately hybridizing two pairs of DNA/RNA hybrids to a DNA scaffold generated by rolling circle amplification for highly efficient in situ siRNA assembly in living cells. After target cell-specific delivery of DNM, intracellular specific microRNA can work as a trigger to operate the DNM by initiating DNA cascade displacement reaction between DNA/RNA hybrids along the scaffold for continuous generation of siRNAs. Using miR-21 as a model, efficient siRNAs generation is achieved via DNA templated cascade reaction, which demonstrated impressive suppressions to VEGF mRNA and protein expressions in cells and in vivo tumor growth and indicated promising application of the designed strategy in gene therapy

Properties and Device Applications of Hydrogenated Amorphous Silicon Carbide Films

Hydrogenated amorphous silicon carbide (a‐SiC:H) films were deposited with a radio‐frequency plasma‐enhanced chemical vapor deposition system which utilizes a dc electric field applied independently of the inductively coupled rf field. The source gases were SiH4 and CH4. It was found that application of an electric field directed out of the substrate surface enhances the growth rate and yields some improvements in photoconductivity. The compositions of the films were evaluated by x‐ray photoelectron spectroscopy for a range of source gas mixtures. In order to assess the applicability of a‐SiC:H thin films, heterojunction a‐SiC:H/crystalline Si (c‐Si) diodes were fabricated and their electrical characteristics evaluated. The diode capacitance‐voltage results confirmed a step junction, which was consistent with the abruptness of the interface demonstrated by high‐resolution transmission electron microscopy. The heterojunction diodes also showed good rectifying properties, suggesting promise for a‐SiC: H in device applications

Recurrence and Polya number of general one-dimensional random walks

The recurrence properties of random walks can be characterized by P\'{o}lya number, i.e., the probability that the walker has returned to the origin at least once. In this paper, we consider recurrence properties for a general 1D random walk on a line, in which at each time step the walker can move to the left or right with probabilities $l$ and $r$, or remain at the same position with probability $o$ ($l+r+o=1$). We calculate P\'{o}lya number $P$ of this model and find a simple expression for $P$ as, $P=1-\Delta$, where $\Delta$ is the absolute difference of $l$ and $r$ ($\Delta=|l-r|$). We prove this rigorous expression by the method of creative telescoping, and our result suggests that the walk is recurrent if and only if the left-moving probability $l$ equals to the right-moving probability $r$.Comment: 3 page short pape