Quantum Mechanics on Spacetime I: Spacetime State Realism

What ontology does realism about the quantum state suggest? The main extant view in contemporary philosophy of physics is wave-function realism. We elaborate the sense in which wave-function realism does provide an ontological picture; and defend it from certain objections that have been raised against it. However, there are good reasons to be dissatisfied with wave-function realism, as we go on to elaborate. This motivates the development of an opposing picture: what we call spacetime state realism; a view which takes the states associated to spacetime regions as fundamental. This approach enjoys a number of beneficial features, although, unlike wave-function realism, it involves non-separability at the level of fundamental ontology. We investigate the pros and cons of this non-separability, arguing that it is a quite acceptable feature; even one which proves fruitful in the context of relativistic covariance. A companion paper discusses the prospects for combining a spacetime-based ontology with separability, along lines suggested by Deutsch and HaydenComment: LaTeX; 29 pages, 1 Fig. Forthcoming in the British Journal for the Philosophy of Scienc

Non-locality and gauge freedom in Deutsch and Hayden's formulation of quantum mechanics

Deutsch and Hayden have proposed an alternative formulation of quantum mechanics which is completely local. We argue that their proposal must be understood as having a form of `gauge freedom' according to which mathematically distinct states are physically equivalent. Once this gauge freedom is taken into account, their formulation is no longer local.Comment: 3 page

Resolution of inflammation:state of the art, definitions and terms

A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution

Role of the C-terminal domain in the structure and function of tetrameric sodium channels.

Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil

Role of the C-terminal domain in the structure and function of tetrameric sodium channels

Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil

The Bionic Bra: Using electromaterials to sense and modify breast support to enhance active living

Background: Although the most supportive sports bras can control breast motion and associated breast pain, they are frequently deemed uncomfortable to wear and, as a result, many women report exercise bra discomfort. Given that exercise bra discomfort is associated with decreased levels of physical activity, there is a pertinent need to develop innovative solutions to address this problem. Objectives: This research aimed to evaluate the use of electromaterial sensors and artificial muscle technology to create a bra that was capable of detecting increases in breast motion and then responding with increased breast support to enhance active living. Methods: The research involved two phases: (i) evaluating sensors suitable for monitoring and providing feedback on changes in the amplitude and frequency of breast motion, and (ii) evaluating an actuator capable of changing breast support provided by a bra during activity. Results: When assessed in isolation, the developed technologies were capable of sensing breast motion and actuating to provide some additional breast support. Conclusions: The challenge now lies in integrating both technologies into a functional sports bra prototype, and assessing this prototype in a controlled biomechanical analysis to provide a breast support solution that will enable women to enjoy active living in comfort

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

Development of a Coaxial 3D Printing Platform for Biofabrication of Implantable Islet-Containing Constructs

Over the last two decades, pancreatic islet transplantations have become a promising treatment for Type I diabetes. However, although providing a consistent and sustained exogenous insulin supply, there are a number of limitations hindering the widespread application of this approach. These include the lack of sufficient vasculature and allogeneic immune attacks after transplantation, which both contribute to poor cell survival rates. Here, these issues are addressed using a biofabrication approach. An alginate/gelatin-based bioink formulation is optimized for islet and islet-related cell encapsulation and 3D printing. In addition, a custom-designed coaxial printer is developed for 3D printing of multicellular islet-containing constructs. In this work, the ability to fabricate 3D constructs with precise control over the distribution of multiple cell types is demonstrated. In addition, it is shown that the viability of pancreatic islets is well maintained after the 3D printing process. Taken together, these results represent the first step toward an improved vehicle for islet transplantation and a potential novel strategy to treat Type I diabetes