Retrograde signaling from autophagy modulates stress responses

Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFκB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and “signalphagy,” which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses

Attention mechanisms in the CHREST cognitive architecture

In this paper, we describe the attention mechanisms in CHREST, a computational architecture of human visual expertise. CHREST organises information acquired by direct experience from the world in the form of chunks. These chunks are searched for, and verified, by a unique set of heuristics, comprising the attention mechanism. We explain how the attention mechanism combines bottom-up and top-down heuristics from internal and external sources of information. We describe some experimental evidence demonstrating the correspondence of CHREST’s perceptual mechanisms with those of human subjects. Finally, we discuss how visual attention can play an important role in actions carried out by human experts in domains such as chess

Smearing of charge fluctuations in a grain by spin-flip assisted tunneling

We investigate the charge fluctuations of a grain (large dot) coupled to a lead via a small quantum dot in the Kondo regime. We show that the strong entanglement of charge and spin flips in this setup can result in a stable SU(4) Kondo fixed point, which considerably smears out the Coulomb staircase behavior already in the weak tunneling limit. This behavior is robust enough to be experimentally observable.Comment: 4 pages, 1 figure, final version for PRB Rapid Com

Infrared problem for the Nelson model on static space-times

We consider the Nelson model with variable coefficients and investigate the problem of existence of a ground state and the removal of the ultraviolet cutoff. Nelson models with variable coefficients arise when one replaces in the usual Nelson model the flat Minkowski metric by a static metric, allowing also the boson mass to depend on position. A physical example is obtained by quantizing the Klein-Gordon equation on a static space-time coupled with a non-relativistic particle. We investigate the existence of a ground state of the Hamiltonian in the presence of the infrared problem, i.e. assuming that the boson mass tends to 0 at infinity

Mesoscopic Fluctuations in Quantum Dots in the Kondo Regime

Properties of the Kondo effect in quantum dots depend sensitively on the coupling parameters and so on the realization of the quantum dot -- the Kondo temperature itself becomes a mesoscopic quantity. Assuming chaotic dynamics in the dot, we use random matrix theory to calculate the distribution of both the Kondo temperature and the conductance in the Coulomb blockade regime. We study two experimentally relevant cases: leads with single channels and leads with many channels. In the single-channel case, the distribution of the conductance is very wide as $T_K$ fluctuates on a logarithmic scale. As the number of channels increases, there is a slow crossover to a self-averaging regime.Comment: 4 pages, 3 figure

Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency

Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

Spin Fluctuation Induced Dephasing in a Mesoscopic Ring

We investigate the persistent current in a hybrid Aharonov-Bohm ring - quantum dot system coupled to a reservoir which provides spin fluctuations. It is shown that the spin exchange interaction between the quantum dot and the reservoir induces dephasing in the absence of direct charge transfer. We demonstrate an anomalous nature of this spin-fluctuation induced dephasing which tends to enhance the persistent current. We explain our result in terms of the separation of the spin from the charge degree of freedom. The nature of the spin fluctuation induced dephasing is analyzed in detail.Comment: 4 pages, 4 figure

On the Global Existence of Bohmian Mechanics

We show that the particle motion in Bohmian mechanics, given by the solution of an ordinary differential equation, exists globally: For a large class of potentials the singularities of the velocity field and infinity will not be reached in finite time for typical initial values. A substantial part of the analysis is based on the probabilistic significance of the quantum flux. We elucidate the connection between the conditions necessary for global existence and the self-adjointness of the Schr\"odinger Hamiltonian.Comment: 35 pages, LaTe

Discriminant Analysis and Secondary-Beam Charge Recognition

The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around 124La and 107Sn were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable 124Sn projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.Comment: 6 pages, 7 eps figures, elsart, submitted to Nucl. Instr. and Meth.