Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy

Neurofibrillary tangles (NFTs) are associated with neuronal loss and correlate with cognitive impairment in Alzheimer disease, but how NFTs relate to neuronal death is not clear. We studied cell death in Tg4510 mice that reversibly express P301L mutant human tau and accumulate NFTs using in vivo multiphoton imaging of neurofibrillary pathology, propidium iodide (PI) incorporation into cells, caspase activation and DNA labeling. We first observed that in live mice a minority of neurons was labeled with the caspase probe or with PI fluorescence. These markers of cell stress were localized in the same cells and appeared to be specifically within NFT-bearing neurons. Contrary to expectations, the PI-stained neurons did not die over a day of observation; the presence of Hoechst-positive nuclei in them on the subsequent day indicated that the NFT-associated membrane disruption suggested by PI staining and caspase activation do not lead to acute death of neurons in this tauopathy model. This unique combination of in vivo multiphoton imaging with markers of cell death and pathologic alteration is a powerful tool for investigating neuronal damage associated with neurofibrillary pathology

Response of Lithographic Mask Structures to Repetitively Pulsed X-rays: Thermal Stress Analysis

This paper examines the effects of thermal loading and time history upon the thermal stresses developed in lithographic mask structures as would be expected under irradiation by intense soft x rays. The objective of this work was to examine the phenomenology of the interaction and to evaluate the limits placed upon mask dosage. The mechanics of mask failure are examined in terms of single pulse and cumulative, or fatigue, effects. A number of prototypical mask structures are investigated, which show that the application of intense pulsed sources to x‐ray lithography does not reduce the potential utility of the techique. However, it is shown that the estimated damage thresholds do impact the operating conditions chosen for optimal production rates and mask lifetime

Dynamics and Transport in Random Antiferromagnetic Spin Chains

We present the first results on the low-frequency dynamical and transport properties of random antiferromagnetic spin chains at low temperature ($T$). We obtain the momentum and frequency dependent dynamic structure factor in the Random Singlet (RS) phases of both spin-1/2 and spin-1 chains, as well as in the Random Dimer phase of spin-1/2 chains. We also show that the RS phases are unusual `spin-metals' with divergent low-frequency conductivity at T=0, and follow the spin conductivity through `metal-insulator' transitions tuned by the strength of dimerization or Ising anisotropy in the spin-1/2 case, and by the strength of disorder in the spin-1 case.Comment: 4 pages (two-column format). Presentation substantially revised to accomodate new result

Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model

Neurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and while they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal function. To investigate the response of cells in hippocampal circuits to complex behavioral stimuli, we used an environmental enrichment paradigm to induce expression of an immediate-early gene, Arc, in the rTg4510 mouse model of tauopathy. These mice reversibly overexpress P301L tau and exhibit substantial neurofibrillary tangle deposition, neuronal loss, and memory deficits. Employing fluorescent in situ hybridization to detect Arc mRNA, we found that rTg4510 mice have impaired hippocampal Arc expression both without stimulation and in response to environmental enrichment; this likely reflects the combination of functional impairments of existing neurons and loss of neurons. However, tangle-bearing cells were at least as likely as non-tangle-bearing neurons to exhibit Arc expression in response to enrichment. Transgene suppression with doxycycline for 6 weeks resulted in increased percentages of Arc-positive cells in rTg4510 brains compared to untreated transgenics, restoring enrichment-induced Arc mRNA levels to that of wild-type controls despite the continued presence of neurofibrillary pathology. We interpret these data to indicate that soluble tau contributes to impairment of hippocampal function, while tangles do not preclude neurons from responding in a functional circuit

Comparison between disordered quantum spin 1/2 chains

We study the magnetic properties of two types of one dimensional XX spin 1/2 chains. The first type has only nearest neighbor interactions which can be either antiferromagnetic or ferromagnetic and the second type which has both nearest neighbor and next nearest neighbor interactions, but only antiferromagnetic in character. We study these systems in the presence of low transverse magnetic fields both analytically and numerically. Comparison of results show a close relation between the two systems, which is in agreement with results previously found in Heisenberg chains by means of a numerical real space renormalization group procedure.Comment: 7 page

Global unions: chasing the dream or building the reality?

This article takes as its theme the global restructuring of capital and its impact on worker organization. It argues for a reassertion of class in any analysis of global solidarity, and assesses the opportunities and barriers to effective global unionization. Rooted in the UK experience, the article analyzes the impact of the European social dimension on trade unions, before taking the discussion into a global dimension. It concludes by suggesting that there are reasons for cautious optimism in terms of solidarity building, despite difficult historical legacies and the common replacement of action with rhetoric

Dynamics and transport in random quantum systems governed by strong-randomness fixed points

We present results on the low-frequency dynamical and transport properties of random quantum systems whose low temperature ($T$), low-energy behavior is controlled by strong disorder fixed points. We obtain the momentum and frequency dependent dynamic structure factor in the Random Singlet (RS) phases of both spin-1/2 and spin-1 random antiferromagnetic chains, as well as in the Random Dimer (RD) and Ising Antiferromagnetic (IAF) phases of spin-1/2 random antiferromagnetic chains. We show that the RS phases are unusual `spin metals' with divergent low-frequency spin conductivity at T=0, and we also follow the conductivity through novel `metal-insulator' transitions tuned by the strength of dimerization or Ising anisotropy in the spin-1/2 case, and by the strength of disorder in the spin-1 case. We work out the average spin and energy autocorrelations in the one-dimensional random transverse field Ising model in the vicinity of its quantum critical point. All of the above calculations are valid in the frequency dominated regime \omega \agt T, and rely on previously available renormalization group schemes that describe these systems in terms of the properties of certain strong-disorder fixed point theories. In addition, we obtain some information about the behavior of the dynamic structure factor and dynamical conductivity in the opposite `hydrodynamic' regime $\omega < T$ for the special case of spin-1/2 chains close to the planar limit (the quantum x-y model) by analyzing the corresponding quantities in an equivalent model of spinless fermions with weak repulsive interactions and particle-hole symmetric disorder.Comment: Long version (with many additional results) of Phys. Rev. Lett. {\bf 84}, 3434 (2000) (available as cond-mat/9904290); two-column format, 33 pages and 8 figure

Griffiths effects and quantum critical points in dirty superconductors without spin-rotation invariance: One-dimensional examples

We introduce a strong-disorder renormalization group (RG) approach suitable for investigating the quasiparticle excitations of disordered superconductors in which the quasiparticle spin is not conserved. We analyze one-dimensional models with this RG and with elementary transfer matrix methods. We find that such models with broken spin rotation invariance {\it generically} lie in one of two topologically distinct localized phases. Close enough to the critical point separating the two phases, the system has a power-law divergent low-energy density of states (with a non-universal continuously varying power-law) in either phase, due to quantum Griffiths singularities. This critical point belongs to the same infinite-disorder universality class as the one dimensional particle-hole symmetric Anderson localization problem, while the Griffiths phases in the vicinity of the transition are controlled by lines of strong (but not infinite) disorder fixed points terminating in the critical point.Comment: 14 pages (two-column PRB format), 9 eps figure