Separation and identification of dominant mechanisms in double photoionization

Double photoionization by a single photon is often discussed in terms of two contributing mechanisms, {\it knock-out} (two-step-one) and {\it shake-off} with the latter being a pure quantum effect. It is shown that a quasi-classical description of knock-out and a simple quantum calculation of shake-off provides a clear separation of the mechanisms and facilitates their calculation considerably. The relevance of each mechanism at different photon energies is quantified for helium. Photoionization ratios, integral and singly differential cross sections obtained by us are in excellent agreement with benchmark experimental data and recent theoretical results.Comment: 4 pages, 5 figure

Peripheral Delivery of a CNS Targeted, Metalo-Protease Reduces Aβ Toxicity in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB. We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein precursor (APP) transgenic model of AD. Treated mice had reduced levels of Aβ, reduced plaques and increased synaptic density in the CNS. Furthermore, mice treated with the neprilysin targeting the CNS had a reversal of memory deficits. Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD

Cognition in Context: Phenomenology, Situated Robotics and the Frame Problem

The frame problem is the difficulty of explaining how non-magical systems think and act in ways that are adaptively sensitive to context-dependent relevance. Influenced centrally by Heideggerian phenomenology, Hubert Dreyfus has argued that the frame problem is, in part, a consequence of the assumption (made by mainstream cognitive science and artificial intelligence) that intelligent behaviour is representation-guided behaviour. Dreyfus’ Heideggerian analysis suggests that the frame problem dissolves if we reject representationalism about intelligence and recognize that human agents realize the property of thrownness (the property of being always already embedded in a context). I argue that this positive proposal is incomplete until we understand exactly how the properties in question may be instantiated in machines like us. So, working within a broadly Heideggerian conceptual framework, I pursue the character of a representationshunning thrown machine. As part of this analysis, I suggest that the frame problem is, in truth, a two-headed beast. The intra-context frame problem challenges us to say how a purely mechanistic system may achieve appropriate, flexible and fluid action within a context. The inter-context frame problem challenges us to say how a purely mechanistic system may achieve appropriate, flexible and fluid action in worlds in which adaptation to new contexts is open-ended and in which the number of potential contexts is indeterminate. Drawing on the field of situated robotics, I suggest that the intra-context frame problem may be neutralized by systems of special purpose adaptive couplings, while the inter-context frame problem may be neutralized by systems that exhibit the phenomenon of continuous reciprocal causation. I also defend the view that while continuous reciprocal causation is in conflict with representational explanation, special-purpose adaptive coupling, as well as its associated agential phenomenology, may feature representations. My proposal has been criticized recently by Dreyfus, who accuses me of propagating a cognitivist misreading of Heidegger, one that, because it maintains a role for representation, leads me seriously astray in my handling of the frame problem. I close by responding to Dreyfus’ concerns

Seeing ‘Where’ through the Ears: Effects of Learning-by-Doing and Long-Term Sensory Deprivation on Localization Based on Image-to-Sound Substitution

BACKGROUND: Sensory substitution devices for the blind translate inaccessible visual information into a format that intact sensory pathways can process. We here tested image-to-sound conversion-based localization of visual stimuli (LEDs and objects) in 13 blindfolded participants. METHODS AND FINDINGS: Subjects were assigned to different roles as a function of two variables: visual deprivation (blindfolded continuously (Bc) for 24 hours per day for 21 days; blindfolded for the tests only (Bt)) and system use (system not used (Sn); system used for tests only (St); system used continuously for 21 days (Sc)). The effect of learning-by-doing was assessed by comparing the performance of eight subjects (BtSt) who only used the mobile substitution device for the tests, to that of three subjects who, in addition, practiced with it for four hours daily in their normal life (BtSc and BcSc); two subjects who did not use the device at all (BtSn and BcSn) allowed assessment of its use in the tasks we employed. The impact of long-term sensory deprivation was investigated by blindfolding three of those participants throughout the three week-long experiment (BcSn, BcSn/c, and BcSc); the other ten subjects were only blindfolded during the tests (BtSn, BtSc, and the eight BtSt subjects). Expectedly, the two subjects who never used the substitution device, while fast in finding the targets, had chance accuracy, whereas subjects who used the device were markedly slower, but showed much better accuracy which improved significantly across our four testing sessions. The three subjects who freely used the device daily as well as during tests were faster and more accurate than those who used it during tests only; however, long-term blindfolding did not notably influence performance. CONCLUSIONS: Together, the results demonstrate that the device allowed blindfolded subjects to increasingly know where something was by listening, and indicate that practice in naturalistic conditions effectively improved "visual" localization performance

Orientation Sensitivity at Different Stages of Object Processing: Evidence from Repetition Priming and Naming

An ongoing debate in the object recognition literature centers on whether the shape representations used in recognition are coded in an orientation-dependent or orientation-invariant manner. In this study, we asked whether the nature of the object representation (orientation-dependent vs orientation-invariant) depends on the information-processing stages tapped by the task

Genetic Variation Shapes Protein Networks Mainly through Non-transcriptional Mechanisms

Variation in the levels of co-regulated proteins that function within networks in an outbred yeast population is not driven by variation in the corresponding transcripts

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency.

BACKGROUND: The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC). METHODS: 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: .9 mm. RESULTS: CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC. CONCLUSIONS: MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS