Prion degradation pathways: Potential for therapeutic intervention

Prion diseases are fatal neurodegenerative disorders. Pathology is closely linked to the misfolding of native cellular PrP(C) into the disease-associated form PrP(Sc) that accumulates in the brain as disease progresses. Although treatments have yet to be developed, strategies aimed at stimulating the degradation of PrP(Sc) have shown efficacy in experimental models of prion disease. Here, we describe the cellular pathways that mediate PrP(Sc) degradation and review possible targets for therapeutic intervention. This article is part of a Special Issue entitled 'Neuronal Protein'

The Lost Tort of Moral Rights Invasion

Moral rights are often portrayed as an unwelcome import into U.S. law. During the nineteenth century, European lawmakers, influenced by personality theories of authorship, began granting authors rights of attribution and integrity. However, while these rights proliferated in Europe and international copyright treaties, they were not adopted in the United States. According to a common historical narrative, U.S. courts and lawmakers resisted moral rights because they were deemed incompatible with the copyright tradition of treating expressive works as alienable property. What little moral rights U.S. law provides today is thus seen as a necessary evil, grudgingly accepted, simply to comply with international obligations. This Article presents a history of moral rights protection that challenges, to a degree, that common historical narrative. The Article tracks how American courts adjudicated attribution and integrity disputes during the twentieth century. Doing so not only reveals that the American judiciary was more sympathetic to these claims than commonly appreciated, but, even more surprisingly, came close to developing a tort of moral rights invasion. While copyright historians know that courts have long provided proxy protection for moral rights under preexisting common law causes of action (e.g., defamation, unfair competition,privacy, etc.), what is not widely known is how frequently courts were willing to protect attribution and integrity interests directly under the banner of moral rights. This Article tells the story of how courts in the mid-twentieth century, applying state law, increasingly articulated a “sui generis tort” of moral rights invasion. It then proceeds to question why the moral rights tort stagnated and was forgotten about in the late twentieth century

Heat current rectification and mobility edges

We investigate how the presence of a single-particle mobility edge in a system can generate strong heat current rectification. Specifically, we study a quadratic bosonic chain subject to a quasi-periodic potential and coupled at its boundaries to spin baths of differing temperature. We find that rectification increases by orders of magnitude depending on the spatial position in the chain of localized eigenstates above the mobility edge. The largest enhancements occur when the coupling of one bath to the system is dominated by a localized eigenstate, while the other bath couples to numerous delocalized eigenstates. By tuning the parameters of the quasi-periodic potential it is thus possible to vary the amplitude, and even invert the direction, of the rectification.Comment: 5+3 pages 4+4 figure

An eccentrically perturbed Tonks-Girardeau gas

We investigate the static and dynamic properties of a Tonks-Girardeau gas in a harmonic trap with an eccentric $\delta$-perturbation of variable strength. For this we first find the analytic eigensolution of the single particle problem and use this solution to calculate the spatial density and energy profiles of the many particle gas as a function of the strength and position of the perturbation. We find that the crystal nature of the Tonks state is reflected in both the lowest occupation number and momentum distribution of the gas. As a novel application of our model, we study the time evolution of the the spatial density after a sudden removal of the perturbation. The dynamics exhibits collapses and revivals of the original density distribution which occur in units of the trap frequency. This is reminiscent of the Talbot effect from classical optics.Comment: Comments and suggestions are welcom

Anisotropic diffusion limited aggregation in three dimensions : universality and nonuniversality

We explore the macroscopic consequences of lattice anisotropy for diffusion limited aggregation (DLA) in three dimensions. Simple cubic and bcc lattice growths are shown to approach universal asymptotic states in a coherent fashion, and the approach is accelerated by the use of noise reduction. These states are strikingly anisotropic dendrites with a rich hierarchy of structure. For growth on an fcc lattice, our data suggest at least two stable fixed points of anisotropy, one matching the bcc case. Hexagonal growths, favoring six planar and two polar directions, appear to approach a line of asymptotic states with continuously tunable polar anisotropy. The more planar of these growths visually resembles real snowflake morphologies. Our simulations use a new and dimension-independent implementation of the DLA model. The algorithm maintains a hierarchy of sphere coverings of the growth, supporting efficient random walks onto the growth by spherical moves. Anisotropy was introduced by restricting growth to certain preferred directions

Work and Quantum Phase Transitions: Is there Quantum Latency?

We study the physics of quantum phase transitions from the perspective of non-equilibrium thermodynamics. For first order quantum phase transitions, we find that the average work done per quench in crossing the critical point is discontinuous. This leads us to introduce the quantum latent work in analogy with the classical latent heat of first order classical phase transitions. For second order quantum phase transitions the irreversible work is closely related to the fidelity susceptibility for weak sudden quenches of the system Hamiltonian. We demonstrate our ideas with numerical simulations of first, second, and infinite order phase transitions in various spin chain models.Comment: accepted in PR

Moral Reflections on Strict Liability in Copyright

Accidental infringement of copyright is a pervasive and largely ignored problem. In the twenty-first century, it has become increasingly easy to infringe copyright unintentionally. When such accidental infringement occurs, copyright law holds the user strictly liable. Prior literature has questioned whether the strict liability standard is normatively defensible. In particular, prior literature has asked whether the strict liability standard ought to be reformed for economic reasons. This Article examines the accidental infringement problem from a new perspective. It considers whether it is fair to hold copyright users strictly liable for accidental infringements of copyright. This Article argues that the strict liability standard is not fair because it results in copyright users being held liable for accidents for which they are not morally responsible. Using the moral philosophy literature on responsibility, this Article explores our intuitions surrounding copyright’s liability standard in order to better understand why strict liability in this context seems “harsh” and “inequitable.” In turn, this provides an argument for reforming copyright’s liability rule and adopting a negligence standard. This Article then argues that, within the United States, the proposed reform to copyright’s liability rule should be accomplished by modifications to the existing fair use doctrine

Water quality and toxicity investigations of two pit lakes at the former Steep Rock iron mines, near Atikokan, Ontario / by Andrea R. Goold.

Caland and Hogarth Pit Lakes formed after cessation of mining and dewatering efforts of open-pit iron mines, near Atikokan, Ontario. They were assessed for w ater quality changes since monitoring began in 1998. Stable isotopes were used to evaluate trends in water columns and gain information on geological processes influencing water quality. Chronic toxicity investigations were carried out for Hogarth Pit Lake. Approaching depths of 200 m, both pits have been filling with groundwater and precipitation since termination of mining in 1979. Limestone and carbonate deposits in the area counter production of acids from waste rocks, resulting in near-neutral pH’s in both lakes. Although proximal pit lakes, there are major chemistry differences between them. Caland is characterized by alkaline, nutrient rich, while Hogarth has elevated conductivity, total dissolved solids (TDS), and S0[subscript 4 superscript 2] levels. Monitoring trends reveal gradual dilution of both pit lakes since 1998. Hogarth has pronounced seasonal variations, with winter months having elevated levels of the aforementioned parameters. Similar δ[superscript34]S profiles in Caland and Hogarth suggest pyritic lenses in the ore body are the major source of sulfates for both lakes. Caland δ[superscript 13]Cdic values reveal organic inputs are the major sources of carbon, whereas Hogarth’s major source of carbon comes from weathering carbonates. Hogarth Pit Lake has experienced a change in toxicity. In 1999 the lake was acutely toxic, and by 2005, chronic effects were present. Chronic toxicity testing using Ceriodaphnia dubia resulted in intermittent toxicity occurring in the winter months. Toxicity Identification Evaluation (TIE) tests did not successfully Isolate the cause of toxicity, which led to exploration of TDS toxicity using mock effluents. Mimicking concentrations of the most abundant ions (Ca[superscript2+], Mg[superscript2+], and SO[subscript 4][superscript 2-]) , mock effluent test results on both C. dubia and Lemna m/nor suggest TDS were responsible for the majority of toxicity in Hogarth. Bioaccumulation studies using Eleocharis smallii and Pyganodon grandis resulted in elevated concentrations of S and Ni in tissues exposed to Hogarth water. Metals contributing to toxicity in Hogarth, especially Ni, could still a possibility and should not be ruled out. Study sites : Caland Pit Lake near the former Caland Ore Company and Hogarth Pit Lake near the former Steep Rock Mines near Atikokan, Northwestern Ontario

Emergent thermodynamics in a quenched quantum many-body system

We study the statistics of the work done, the fluctuation relations and the irreversible entropy production in a quantum many-body system subject to the sudden quench of a control parameter. By treating the quench as a thermodynamic transformation we show that the emergence of irreversibility in the nonequilibrium dynamics of closed many-body quantum systems can be accurately characterized. We demonstrate our ideas by considering a transverse quantum Ising model that is taken out of equilibrium by the instantaneous switching of the transverse field.Comment: 6 pages, 1 figur

An ITPR1 gene deletion causes SCA15 and 16; a genetic, clinical and radiological description

Spinocerebellar ataxia (SCA) 15/16 is an autosomal dominantly inherited, almost pure cerebellar ataxia, which shows slow or no progression. (It has been designated variably SCA15 and SCA 16; we refer to it here as SCA15/16 to avoid confusion). Deletions in the inositol 1, 4, 5-triphosphate receptor 1 (ITPR1) on chromosome 3 have been shown to cause SCA15/16 in six families worldwide to date, with one further Japanese family identified as having an ITPR1 point mutation. We present a previously unreported SCA15/16 kindred. We describe the clinical phenotype of the family in detail; affected subjects display a remarkably slow, almost pure cerebellar syndrome. We also present genetic analyses for all subjects and longitudinal MRI data for one affected subject. Genetic analysis shows a deletion of 346,487bp in ITPR1 (the second largest ITPR1 deletion reported to date), suggesting SCA15 is due to a loss of ITPR1 function, and western blotting of lymphoblastoid cell line protein confirms reduced ITPR1 protein levels. Serial MRIs show progressive midline cerebellar atrophy with mild inferior parietal and temporal cortical volume loss in the absence of clinical disease progression. We believe that genetic testing for SCA15/16 should become a routine DNA screen available in all Neurogenetics clinics, which is likely to lead to an increased rate of the diagnosis. Familiarity with the phenotype is therefore important for all neurologists