Rapid cell-surface prion protein conversion revealed using a novel cell system

Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion

On defining the Hamiltonian beyond quantum theory

Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease.

CAG repeat expansion in the HTT gene drives Huntington's disease (HD) pathogenesis and is modulated by DNA damage repair pathways. In this context, the interaction between FAN1, a DNA-structure-specific nuclease, and MLH1, member of the DNA mismatch repair pathway (MMR), is not defined. Here, we identify a highly conserved SPYF motif at the N terminus of FAN1 that binds to MLH1. Our data support a model where FAN1 has two distinct functions to stabilize CAG repeats. On one hand, it binds MLH1 to restrict its recruitment by MSH3, thus inhibiting the assembly of a functional MMR complex that would otherwise promote CAG repeat expansion. On the other hand, it promotes accurate repair via its nuclease activity. These data highlight a potential avenue for HD therapeutics in attenuating somatic expansion

Teleportation of a quantum state of a spatial mode with a single massive particle

Mode entanglement exists naturally between regions of space in ultra-cold atomic gases. It has, however, been debated whether this type of entanglement is useful for quantum protocols. This is due to a particle number superselection rule that restricts the operations that can be performed on the modes. In this paper, we show how to exploit the mode entanglement of just a single particle for the teleportation of an unknown quantum state of a spatial mode. We detail how to overcome the superselection rule to create any initial quantum state and how to perform Bell state analysis on two of the modes. We show that two of the four Bell states can always be reliably distinguished, while the other two have to be grouped together due to an unsatisfied phase matching condition. The teleportation of an unknown state of a quantum mode thus only succeeds half of the time.Comment: 12 pages, 1 figure, this paper was presented at TQC 2010 and extends the work of Phys. Rev. Lett. 103, 200502 (2009

Second law, entropy production, and reversibility in thermodynamics of information

We present a pedagogical review of the fundamental concepts in thermodynamics of information, by focusing on the second law of thermodynamics and the entropy production. Especially, we discuss the relationship among thermodynamic reversibility, logical reversibility, and heat emission in the context of the Landauer principle and clarify that these three concepts are fundamentally distinct to each other. We also discuss thermodynamics of measurement and feedback control by Maxwell's demon. We clarify that the demon and the second law are indeed consistent in the measurement and the feedback processes individually, by including the mutual information to the entropy production.Comment: 43 pages, 10 figures. As a chapter of: G. Snider et al. (eds.), "Energy Limits in Computation: A Review of Landauer's Principle, Theory and Experiments

Anderson localisation in spin chains for perfect state transfer

Abstract: Anderson localisation is an important phenomenon arising in many areas of physics, andhere we explore it in the context of quantum information devices. Finite dimensional spinchains have been demonstrated to be important devices for quantum information transport,and in particular can be engineered to allow for “perfect state transfer” (PST). Here wepresent extensive investigations of disordered PST spin chains, demonstrating spatiallocalisation and transport retardation effects, and relate these effects to conventionalAnderson localisation. We provide thresholds for Anderson localisation in these finitequantum information systems for both the spatial and the transport domains. Finally, weconsider the effect of disorder on the eigenstates and energy spectrum of our Hamiltonian,where results support our conclusions on the presence of Anderson localisation. Graphical abstract: [Figure not available: see fulltext.

Eigenvectors under a generic perturbation: non-perturbative results from the random matrix approach

We consider eigenvectors of the Hamiltonian H0 perturbed by a generic perturbation V modelled by a random matrix from the Gaussian Unitary Ensemble (GUE). Using the super-symmetry approach we derive analytical results for the statistics of the eigenvectors, which are non-perturbative in V and valid for an arbitrary deterministic H0. Further we generalise them to the case of a random H0, focusing, in particular, on the Rosenzweig-Porter model. Our analytical predictions are confirmed by numerical simulations

Cost-consciousness among Swiss doctors: a cross-sectional survey

BACKGROUND: Knowing what influences physicians attitudes toward health care costs is an important matter, because most health care expenditures are the results of doctors' decisions. Many decisions regarding medical tests and treatments are influenced by factors other than the expected benefit to the patient, including the doctor's demographic characteristics and concerns about cost and income. METHODS: Doctors (n = 1184) in Geneva, Switzerland, answered questions about their cost-consciousness, practice patterns (medical specialty, public.vs. private sector, number of patients per week, time spent with a new patient), work satisfaction, and stress from uncertainty. General linear models were used to identify independent risk factors of higher cost-consciousness. RESULTS: Most doctors agreed that trying to contain costs was their responsibility ("agree" or "totally agree": 90%) and that they should take a more prominent role in limiting the use of unnecessary tests (92%); most disagreed that doctors are too busy to worry about costs (69%) and that the cost of health care is only important if the patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost-consciousness was higher among doctors in the public sector, those who saw fewer patients per week, who were most tolerant of uncertainty, and who were most satisfied with their work. CONCLUSION: Thus even in a setting with very high health care expenditures, doctors' stated cost-consciousness appeared to be generally high, even though it was not uniformly distributed among them

What effect does physician "profiling" have on inpatient physician satisfaction and hospital length of stay?

BACKGROUND: 2002 marked the first time that the rate of hospital spending in the United States outpaced the overall health care spending rate of growth since 1991. As hospital spending continues to grow and as reimbursement for hospital expenses has moved towards the prospective payment system, there is still increasing pressure to reduce costs. Hospitals have a major incentive to decrease resource utilization, including hospital length of stay. We evaluated whether physician profiling affects physician satisfaction and hospital length of stay, and assessed physicians' views concerning hospital cost containment and the quality of care they provide. METHODS: To determine if physician profiling affects hospital length of stay and/or physician satisfaction, we used quasi-experimental with before-versus-after and intervention-versus-control comparisons of length of stay data collected at an intervention and six control hospitals. Intervention hospital physicians were informed their length of stay would be compared to their peers and were given a questionnaire assessing their experience. RESULTS: Nearly half of attending pre-profiled physicians felt negative about the possibility of being profiled, while less than one-third of profiled physicians reported feeling negative about having been profiled. Nearly all physicians greatly enjoyed their ward month. Length of stay at the profiled site decreased by an additional 1/3 of a day in the profiling year, compared to the non-profiled sites (p < 0.001). CONCLUSION: A relatively non-instrusive profiling intervention modestly reduced length of stay without adversely affecting physician satisfaction

Structural versus experienced complexity: a new perspective on the relationship between organizational complexity and innovation

In this paper, we explore the relationship between organizational complexity and firm-level innovation. We define and operationalize a new construct, experienced complexity, which is the extent to which the organizational environment makes it challenging for decision-makers to do their jobs effectively. We distinguish experienced complexity from structural complexity, which is the elements of the organization, such as the number of reporting lines or integrating mechanisms, that are deliberately put in place to help the organization deliver on its objectives, and we argue that structural complexity correlates positively with firm-level innovation while experienced complexity correlates negatively with innovation. Using a novel dataset combining survey and objective data on 209 large firms, we find support for our arguments