An Extensive Study of User Identification via Eye Movements across Multiple Datasets

Several studies have reported that biometric identification based on eye movement characteristics can be used for authentication. This paper provides an extensive study of user identification via eye movements across multiple datasets based on an improved version of method originally proposed by George and Routray. We analyzed our method with respect to several factors that affect the identification accuracy, such as the type of stimulus, the IVT parameters (used for segmenting the trajectories into fixation and saccades), adding new features such as higher-order derivatives of eye movements, the inclusion of blink information, template aging, age and gender.We find that three methods namely selecting optimal IVT parameters, adding higher-order derivatives features and including an additional blink classifier have a positive impact on the identification accuracy. The improvements range from a few percentage points, up to an impressive 9 % increase on one of the datasets.Comment: 11 pages, 5 figures, submitted to Signal Processing: Image Communicatio

Modulating medial prefrontal cortex activity using real-time fMRI neurofeedback: Effects on reality monitoring performance and associated functional connectivity

Neuroimaging studies have found ‘reality monitoring’, our ability to distinguish internally generated experiences from those derived from the external world, to be associated with activity in the medial prefrontal cortex (mPFC) of the brain. Here we probe the functional underpinning of this ability using real-time fMRI neurofeedback to investigate the involvement of mPFC in recollection of the source of self-generated information. Thirty-nine healthy individuals underwent neurofeedback training in a between groups study receiving either Active feedback derived from the paracingulate region of the mPFC (21 subjects) or Sham feedback based on a similar level of randomised signal (18 subjects). Compared to those in the Sham group, participants receiving Active signal showed increased mPFC activity over the course of three real-time neurofeedback training runs undertaken in a single scanning session. Analysis of resting state functional connectivity associated with changes in reality monitoring accuracy following Active neurofeedback revealed increased connectivity between dorsolateral frontal regions of the fronto-parietal network (FPN) and the mPFC region of the default mode network (DMN), together with reduced connectivity within ventral regions of the FPN itself. However, only a trend effect was observed in the interaction of the recollection of the source of Imagined information compared with recognition memory between participants receiving Active and Sham neurofeedback, pre- and post- scanning. As such, these findings demonstrate that neurofeedback can be used to modulate mPFC activity and increase cooperation between the FPN and DMN, but the effects on reality monitoring performance are less clear

Interaction between dislocation and coherent twin boundary by quasicontinuum model

The interaction between lattice dislocations and Coherent Twin Boundary Σ3{111} of copper has been studied using Quasi-Continuum method. The coherent twin boundary provides high barrier to slip transmission. The dislocation pile-up modifies the stress field at its intersection with the grain boundary. A different reaction process compared with the case of single dislocations is noticed. One observes the nucleation of a Lomer-type dislocation with Burgers vector of ½ and its glide on the (100) cube plane in the adjacent grain. This phenomenon has been observed with Transmission Electron Microscopy at room temperature and in other Molecular Dynamics simulations. We also show a novel interaction mechanism between Lomer-type dislocation and Coherent Twin Boundary. This interaction process leaves a dislocation with a Burgers vector coincident with the complete lattice shift of the Coherent Twin Boundary. Quantitative estimation of critical stress for various transmission phenomena is performed by using irial stress. Such information can be used as input for Discrete Dislocation Dynamics model

Butyrate Attenuates Lipopolysaccharide-Induced Inflammation in Intestinal Cells and Crohn's Mucosa through Modulation of Antioxidant Defense Machinery

Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia Coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa

Positive Evolutionary Selection of an HD Motif on Alzheimer Precursor Protein Orthologues Suggests a Functional Role

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the “transcription binding site turnover.” CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs

RNA Aptamers Generated against Oligomeric Aβ40 Recognize Common Amyloid Aptatopes with Low Specificity but High Sensitivity

Aptamers are useful molecular recognition tools in research, diagnostics, and therapy. Despite promising results in other fields, aptamer use has remained scarce in amyloid research, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disease believed to be caused by neurotoxic amyloid β-protein (Aβ) oligomers. Aβ oligomers therefore are an attractive target for development of diagnostic and therapeutic reagents. We used covalently-stabilized oligomers of the 40-residue form of Aβ (Aβ40) for aptamer selection. Despite gradually increasing the stringency of selection conditions, the selected aptamers did not recognize Aβ40 oligomers but reacted with fibrils of Aβ40, Aβ42, and several other amyloidogenic proteins. Aptamer reactivity with amyloid fibrils showed some degree of protein-sequence dependency. Significant fibril binding also was found for the naïve library and could not be eliminated by counter-selection using Aβ40 fibrils, suggesting that aptamer binding to amyloid fibrils was RNA-sequence-independent. Aptamer binding depended on fibrillogenesis and showed a lag phase. Interestingly, aptamers detected fibril formation with ≥15-fold higher sensitivity than thioflavin T (ThT), revealing substantial β-sheet and fibril formation undetected by ThT. The data suggest that under physiologic conditions, aptamers for oligomeric forms of amyloidogenic proteins cannot be selected due to high, non-specific affinity of oligonucleotides for amyloid fibrils. Nevertheless, the high sensitivity, whereby aptamers detect β-sheet formation, suggests that they can serve as superior amyloid recognition tools

Towards a Pharmacophore for Amyloid

Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist of pairs of β-sheets, with small molecules binding between the sheets, roughly parallel to the fiber axis. The structures suggest that apolar molecules drift along the fiber, consistent with the observation of nonspecific binding to a variety of amyloid proteins. In contrast, negatively charged orange-G binds specifically to lysine side chains of adjacent sheets. These structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases