Revisiting graphical passwords for augmenting, not replacing, text passwords

Users generally choose weak passwords which can be easily guessed. On the other hand, adoption of alternatives to text passwords has been slow due to cost and usability factors. We acknowledge that incumbent passwords remain difficult to beat and introduce in this study Type&Click (T&C), a hybrid scheme supporting text passwords with the graphical passwords. In T&C, users first type a text as usual and then make a single click on an image to complete the password entry. While largely preserving the login experience with the text passwords, the new scheme utilizes accumulated scientific knowledge in graphical password research (implicit feedback, persuasion during password creation, leveraging cued recall memory). The results of our user study suggest that T&C is promising for augmenting text passwords for improved security without degrading usability. Copyright 2013 ACM

Effect of Zoledronic Acid on Rats' Tissue Sdf-1 Expression

Zoledronic acid has been shown to inhibit cancer cell proliferation, metastasis and induce cancer cell apoptosis. Stromal Derived Factor-1 (SDF-1) is a chemokine that has been reported to be expressed markedly high in the most common metastatic sites. The aim of this study was to investigate the effect of zoledronic acid on SDF-1 mRNA expression of rats' tissues. Rats were randomised into two groups, each containing five rats. Zoledronic acid was administered 0.1 mg/kg subcutaneously to one group. Other group was used as the control group. Seven days later, all rats were sacrificed. Levels of SDF-1 mRNA expression in tissues were measured quantitatively with RT-PCR. The median of SDF-1 mRNA relative expression in the lung was 0.80 (0.49-1.00) in the control group and 0.90 (0.61-1.42) in the zoledronic acid group (p=0.53). The median of SDF-1 mRNA relative expression in the liver was 0.90 (0.39-1.00) in the control group and 0.93 (0.77-1.29) in the zoledronic acid group (p=0.35). In this study, we investigated the effect of zoledronic acid on the tissue SDF-1 mRNA expression for the first time in the literature. We observed that a single dose of zoledronic acid did not change SDF-1 expression in lung and liver of rats.WoSScopu

Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD.

Duchenne muscular dystrophy is a fatal muscle disease, caused by mutations in DMD, leading to loss of dystrophin expression. Phosphorodiamidate morpholino splice-switching oligonucleotides (PMO-SSOs) have been used to elicit the restoration of a partially functional truncated dystrophin by excluding disruptive exons from the DMD messenger. The 30-mer PMO eteplirsen (EXONDYS51) developed for exon 51 skipping is the first dystrophin-restoring, conditionally FDA-approved drug in history. Clinical trials had shown a dose-dependent variable and patchy dystrophin restoration. The main obstacle for efficient dystrophin restoration is the inadequate uptake of PMOs into skeletal muscle fibers at low doses. The excessive cost of longer PMOs has limited the utilization of higher dosing. We designed shorter 25-mer PMOs directed to the same eteplirsen-targeted region of exon 51 and compared their efficacies in vitro and in vivo in the mdx52 murine model. Our results showed that skipped-dystrophin induction was comparable between the 30-mer PMO sequence of eteplirsen and one of the shorter PMOs, while the other 25-mer PMOs showed lower exon-skipping efficacies. Shorter PMOs would make higher doses economically feasible, and high dosing would result in better drug uptake into muscle, induce higher levels of dystrophin restoration in DMD muscle, and, ultimately, increase the clinical efficacy. Keywords: DMD, dystrophin, exon skipping, eteplirsen, phosphorodiamidate morpholino, PMO, shorter PMO-SSOs, phosphorothiorate, myopathy, exondys51, md

The role of dopamine(2) receptor gene and personality characteristics in alcohol dependence in Turkish population

WOS: 000340477600002Objective: Focusing on dopaminergic system, which is regarded to be responsible for alcohol dependence in many studies on animals and human beings, it is aimed to investigate Taql A and 8 allel polymorphisms of dopamine 2 receptor and personality characteristics in alcohol dependents and the relationship between these two parameters. Methods: In this study 64 alcohol dependent patients (3 females, 61 males) diagnosed according to DSM-IV diagnosis criteria, and 54 healthy subjects (8 females, 46 males) who themselves or whose first or second degree relatives had no alcohol dependence history were included. In order to determine their Taql A and 8 alleles, blood samples were drawn from the participants, and then they were applied Temperament and Character Inventory and Michigan Alcoholism Screening Test. Results: Subjects with and without alcohol dependence revealed no significant difference as regards the frequency of Taql A1 and B2 minor allel polymorphisms of DRD2 gene. It was also determined that the alcohol dependents had significantly higher scores in novelty seeking and harm avoidance dimensions, and lower scores in self directedness and cooperativeness dimensions than the controls. In alcohol dependents, no association was determined between the personality characteristics and Taql A1 and B2 minor allel polymorphisms. Conclusion: Not only one gene, but also several other minor genes in addition to personality characteristics and environment may play a role in vulnerability to alcohol dependence. In alcohol dependents, high novelty seeking is associated with the increase in impulsive behavior, and may be important for the onset of alcohol taking behavior. High level of harm avoidance may lead to taking alcohol continuously in order to deal with stress

Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey

Congenital myopathies (CMs) are a heterogeneous group of inherited muscle disorders characterized by muscle weakness at birth, while limb-girdle muscular dystrophies (LGMD) have a later onset and slower disease progression. Thus, detailed clinical phenotyping of genetically defined disease entities are required for the full understanding of genotype-phenotype correlations. A recently defined myopathic genetic disease entity is caused by bi-allelic variants in a gene coding for pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) with unknown substrates. Here, we present three patients from two consanguineous Turkish families with mild LGMD, facial weakness, normal CK levels, and slow progress. Genomic analyses revealed a homozygous known pathogenic missense variant (c.464A>G, p.Asn155Ser) in family 1 with two affected females. In the affected male of family 2, we found this variant in a compound heterozygous state together with a novel frameshift variant (c.329_332delTCTG, p.Leu112Valfs*8), which is the second frameshift variant known so far in PYROXD1. We have been able to define a large homozygous region in family 1 sharing a common haplotype with family 2 in the critical region. Our data suggest that c.464A>G is a Turkish founder mutation. To gain deeper insights, we performed a systematic review of all published PYROXD1-related myopathy cases. Our analysis showed that the c.464A > G variant was found in 87% (20/23) of the patients and that it may cause either a childhood- or adult-onset phenotype, irrespective of its presence in a homozygous or compound heterozygous state. Interestingly, only four patients had elevated CK levels (up to 1000 U/L), and cardiac involvement was found in few compound heterozygous cases

Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection

Erratum: Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome (The American Journal of Human Genetics (2018) 103(3) (431–439)(S0002929718302374)(10.1016/j.ajhg.2018.07.010))

(The American Journal of Human Genetics 103, 431–439; September 6, 2018) In the original version of this article, author Tracy Dixon-Salazar's name was incomplete. It now appears correctly here and online. The authors regret the error