Analysis of heat shock-, sodium arsenite- and proteasome inhibitor-induced heat shock protein gene expression in Xenopus laevis

Previous studies have focused on the effect of individual stressors on hsp gene expression in eukaryotic organisms. In the present study, I examined the effect of concurrent low doses of sodium arsenite and mild heat shock temperatures on the expression of hsp30 and hsp70 genes in Xenopus laevis A6 kidney epithelial cells. Northern hybridization and western blot analysis revealed that exposure of A6 cells to 1-10 μM sodium arsenite at a mild heat shock temperature of 30˚C enhanced hsp30 and hsp70 gene expression to a much greater extent than found with either stress individually. In cells treated simultaneously with 10 μM sodium arsenite and different heat shock temperatures, enhanced accumulation of HSP30 and HSP70 protein was first detected at 26˚C with larger responses at 28 and 30 ˚C. HSF1 activity was involved in combined stress-induced hsp gene expression since the HSF1 activation inhibitor, KNK437, inhibited HSP30 and HSP70 accumulation. Immunocytochemical analysis revealed that HSP30 was present in a granular pattern primarily in the cytoplasm in cells treated simultaneously with both stresses. Finally, prior exposure of A6 cells to concurrent sodium arsenite (10 μM ) and heat shock (30 ˚C) treatment conferred thermotolerance since it protected them against a subsequent thermal challenge at 37 ˚C. Acquired thermotolerance was not observed with cells treated with the two mild stresses individually. It is likely that the enhanced accumulation of HSPs under these conditions permits the organism to cope with multiple environmental stresses encountered in their natural aquatic habitat. Previous studies have shown that inhibiting the activity of the proteasome also leads to the accumulation of damaged or unfolded proteins within the cell. In the second phase of this study, I report that inhibition of proteasome activity by the inhibitors carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and lactacystin induced the accumulation of HSP30 and HSP70 as well as their respective mRNAs. The accumulation of HSP30 and HSP70 in A6 cells recovering from MG132 exposure was still relatively high 24 h after treatment and it decreased substantially after 48 h. Exposing A6 cells to simultaneous MG132 and mild heat shock enhanced the accumulation of HSP30 and HSP70 to a much greater extent than with each stressor alone. HSP30 localization in A6 cells was primarily in the cytoplasm as revealed by immunocytochemistry. In some A6 cells treated with higher concentrations of MG132 and lactacystin, HSP30 was also found to localize in relatively large cytoplasmic foci. In some MG132-treated cells, HSP30 staining was substantially depleted in the cytoplasmic regions surrounding these foci. The activation of HSF1 may be involved in MG132-induced hsp gene expression in A6 cells since KNK437 inhibited the accumulation of HSP30 and HSP70. Lastly, MG132 treatment also conferred a state of thermotolerance in A6 cells such that they were able to survive a subsequent thermal challenge. Analysis of this phenomenon is important given the fact that impaired proteasomal activity has been suggested as an explanation for some of the late-onset neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease

The quantum world is not built up from correlations

It is known that the global state of a composite quantum system can be completely determined by specifying correlations between measurements performed on subsystems only. Despite the fact that the quantum correlations thus suffice to reconstruct the quantum state, we show, using a Bell inequality argument, that they cannot be regarded as objective local properties of the composite system in question. It is well known since the work of J.S. Bell, that one cannot have locally preexistent values for all physical quantities, whether they are deterministic or stochastic. The Bell inequality argument we present here shows this is also impossible for correlations among subsystems of an individual isolated composite system. Neither of them can be used to build up a world consisting of some local realistic structure. As a corrolary to the result we argue that entanglement cannot be considered ontologically robust. The argument has an important advantage over others because it does not need perfect correlations but only statistical correlations. It can therefore easily be tested in currently feasible experiments using four particle entanglement.Comment: Published version. Title change

Geometrical properties of Riemannian superspaces, observables and physical states

Classical and quantum aspects of physical systems that can be described by Riemannian non degenerate superspaces are analyzed from the topological and geometrical points of view. For the N=1 case the simplest supermetric introduced in [Physics Letters B \textbf{661}, (2008),186] have the correct number of degrees of freedom for the fermion fields and the super-momentum fulfil the mass shell condition, in sharp contrast with other cases in the literature where the supermetric is degenerate. This fact leads a deviation of the 4-impulse (e.g. mass constraint) that can be mechanically interpreted as a modification of the Newton's law. Quantum aspects of the physical states and the basic states and the projection relation between them, are completely described due the introduction of a new Majorana-Weyl representation of the generators of the underlying group manifold. A new oscillatory fermionic effect in the $B_{0}$ part of the vaccum solution involving the chiral and antichiral components of this Majorana bispinor is explicitly shown.Comment: 16 pags. 3 figures. To Anna Grigorievna Kartavenko and Academic Professor Alexei Norianovich Sissakian, in memoria

Relational Hidden Variables and Non-Locality

We use a simple relational framework to develop the key notions and results on hidden variables and non-locality. The extensive literature on these topics in the foundations of quantum mechanics is couched in terms of probabilistic models, and properties such as locality and no-signalling are formulated probabilistically. We show that to a remarkable extent, the main structure of the theory, through the major No-Go theorems and beyond, survives intact under the replacement of probability distributions by mere relations.Comment: 42 pages in journal style. To appear in Studia Logic

UK Public Sector Information and Re-use Policy – A 2008 Analysis

INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority

Real measurements and Quantum Zeno effect

In 1977, Mishra and Sudarshan showed that an unstable particle would never be found decayed while it was continuously observed. They called this effect the quantum Zeno effect (or paradox). Later it was realized that the frequent measurements could also accelerate the decay (quantum anti-Zeno effect). In this paper we investigate the quantum Zeno effect using the definite model of the measurement. We take into account the finite duration and the finite accuracy of the measurement. A general equation for the jump probability during the measurement is derived. We find that the measurements can cause inhibition (quantum Zeno effect) or acceleration (quantum anti-Zeno effect) of the evolution, depending on the strength of the interaction with the measuring device and on the properties of the system. However, the evolution cannot be fully stopped.Comment: 3 figure

Diameters in preferential attachment models

In this paper, we investigate the diameter in preferential attachment (PA-) models, thus quantifying the statement that these models are small worlds. The models studied here are such that edges are attached to older vertices proportional to the degree plus a constant, i.e., we consider affine PA-models. There is a substantial amount of literature proving that, quite generally, PA-graphs possess power-law degree sequences with a power-law exponent \tau>2. We prove that the diameter of the PA-model is bounded above by a constant times \log{t}, where t is the size of the graph. When the power-law exponent \tau exceeds 3, then we prove that \log{t} is the right order, by proving a lower bound of this order, both for the diameter as well as for the typical distance. This shows that, for \tau>3, distances are of the order \log{t}. For \tau\in (2,3), we improve the upper bound to a constant times \log\log{t}, and prove a lower bound of the same order for the diameter. Unfortunately, this proof does not extend to typical distances. These results do show that the diameter is of order \log\log{t}. These bounds partially prove predictions by physicists that the typical distance in PA-graphs are similar to the ones in other scale-free random graphs, such as the configuration model and various inhomogeneous random graph models, where typical distances have been shown to be of order \log\log{t} when \tau\in (2,3), and of order \log{t} when \tau>3

Projection Postulate and Atomic Quantum Zeno Effect

The projection postulate has been used to predict a slow-down of the time evolution of the state of a system under rapidly repeated measurements, and ultimately a freezing of the state. To test this so-called quantum Zeno effect an experiment was performed by Itano et al. (Phys. Rev. A 41, 2295 (1990)) in which an atomic-level measurement was realized by means of a short laser pulse. The relevance of the results has given rise to controversies in the literature. In particular the projection postulate and its applicability in this experiment have been cast into doubt. In this paper we show analytically that for a wide range of parameters such a short laser pulse acts as an effective level measurement to which the usual projection postulate applies with high accuracy. The corrections to the ideal reductions and their accumulation over n pulses are calculated. Our conclusion is that the projection postulate is an excellent pragmatic tool for a quick and simple understanding of the slow-down of time evolution in experiments of this type. However, corrections have to be included, and an actual freezing does not seem possible because of the finite duration of measurements.Comment: 25 pages, LaTeX, no figures; to appear in Phys. Rev.

On Relativistic Quantum Information Properties of Entangled Wave Vectors of Massive Fermions

We study special relativistic effects on the entanglement between either spins or momenta of composite quantum systems of two spin-1/2 massive particles, either indistinguishable or distinguishable, in inertial reference frames in relative motion. For the case of indistinguishable particles, we consider a balanced scenario where the momenta of the pair are well-defined but not maximally entangled in the rest frame while the spins of the pair are described by a one-parameter ($\eta$) family of entangled bipartite states. For the case of distinguishable particles, we consider an unbalanced scenario where the momenta of the pair are well-defined and maximally entangled in the rest frame while the spins of the pair are described by a one-parameter ($\xi$) family of non-maximally entangled bipartite states. In both cases, we show that neither the spin-spin ($ss$) nor the momentum-momentum ($mm$) entanglements quantified by means of Wootters' concurrence are Lorentz invariant quantities: the total amount of entanglement regarded as the sum of these entanglements is not the same in different inertial moving frames. In particular, for any value of the entangling parameters, both $ss$ and $mm$-entanglements are attenuated by Lorentz transformations and their parametric rates of change with respect to the entanglements observed in a rest frame have the same monotonic behavior. However, for indistinguishable (distinguishable) particles, the change in entanglement for the momenta is (is not) the same as the change in entanglement for spins. As a consequence, in both cases, no entanglement compensation between spin and momentum degrees of freedom occurs.Comment: 21 pages, 8 figure

Quantum mechanics: Myths and facts

A common understanding of quantum mechanics (QM) among students and practical users is often plagued by a number of "myths", that is, widely accepted claims on which there is not really a general consensus among experts in foundations of QM. These myths include wave-particle duality, time-energy uncertainty relation, fundamental randomness, the absence of measurement-independent reality, locality of QM, nonlocality of QM, the existence of well-defined relativistic QM, the claims that quantum field theory (QFT) solves the problems of relativistic QM or that QFT is a theory of particles, as well as myths on black-hole entropy. The fact is that the existence of various theoretical and interpretational ambiguities underlying these myths does not yet allow us to accept them as proven facts. I review the main arguments and counterarguments lying behind these myths and conclude that QM is still a not-yet-completely-understood theory open to further fundamental research.Comment: 51 pages, pedagogic review, revised, new references, to appear in Found. Phy