4,186 research outputs found
The Real Combination Problem : Panpsychism, Micro-Subjects, and Emergence
Panpsychism harbors an unresolved tension, the seriousness of which has yet to be fully appreciated. I capture this tension as a dilemma, and offer panpsychists advice on how to resolve it. The dilemma, briefly, is as follows. Panpsychists are committed to the perspicuous explanation of macro-mentality in terms of micro-mentality. But panpsychists take the micro-material realm to feature not just mental properties, but also micro-subjects to whom these properties belong. Yet it is impossible to explain the constitution of a macro-subject (like one of us) in terms of the assembly of micro-subjects, for, I show, subjects cannot combine. Therefore the panpsychist explanatory project is derailed by the insistence that the world’s ultimate material constituents (ultimates) are subjects of experience. The panpsychist faces a choice of abandoning her explanatory project, or recanting the claim that the ultimates are subjects. This is the dilemma. I argue that the latter option is to be preferred. This needn’t constitute a wholesale abandonment of panpsychism, however, since panpsychists can maintain that the ultimates possess phenomenal qualities, despite not being subjects of those qualities. This proposal requires us to make sense of phenomenal qualities existing independently of experiencing subjects, a challenge I tackle in the penultimate section. The position eventually reached is a form of neutral monism, so another way to express the overall argument is to say that, keeping true to their philosophical motivations, panpsychists should really be neutral monists.Peer reviewedFinal Accepted Versio
RNA editing regulates insect gamma-aminobutyric acid receptor function and insecticide sensitivity
A-to-I pre-mRNA editing by adenosine deaminase enzymes has been reported to enhance protein diversity in the nervous system. In Drosophila, the resistance to dieldrin (RDL) gamma-aminobutyric acid (GABA) receptor subunit displays an editing site (R122) that is close to the putative GABA-binding site. We assessed the functional effects of editing at this site by expressing homomeric RDL receptors in Xenopus oocytes. After replacement of arginine 122 with a glycine, both agonist and fipronil potencies were shifted to the right in either fipronil-sensitive receptors or mutated resistant receptors (A301G/T350M). These data provide the first insight on the influence of RNA editing on GABA receptor function
Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity
The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments
Spin correlations and exchange in square lattice frustrated ferromagnets
The J1-J2 model on a square lattice exhibits a rich variety of different
forms of magnetic order that depend sensitively on the ratio of exchange
constants J2/J1. We use bulk magnetometry and polarized neutron scattering to
determine J1 and J2 unambiguously for two materials in a new family of vanadium
phosphates, Pb2VO(PO4)2 and SrZnVO(PO4)2, and we find that they have
ferromagnetic J1. The ordered moment in the collinear antiferromagnetic ground
state is reduced, and the diffuse magnetic scattering is enhanced, as the
predicted bond-nematic region of the phase diagram is approached.Comment: 4 pages, 4 figure
The phase diagram of the lattice Calogero-Sutherland model
We introduce a {\it lattice} version of the Calogero Sutherland model adapted
to describe pairwise interacting steps with discrete positions on a
vicinal surface. The configurational free energy is obtained within a transfer
matrix method. The full phase diagram for attractive and for repulsive
interaction is deduced. For attraction, critical temperatures of faceting
transitions are found to depend on step density.Comment: latex PRBCalogSuth.tex, 6 files, 4 pages [SPEC-S00/900
Classical simulation of measurement-based quantum computation on higher-genus surface-code states
We consider the efficiency of classically simulating measurement-based
quantum computation on surface-code states. We devise a method for calculating
the elements of the probability distribution for the classical output of the
quantum computation. The operational cost of this method is polynomial in the
size of the surface-code state, but in the worst case scales as in the
genus of the surface embedding the code. However, there are states in the
code space for which the simulation becomes efficient. In general, the
simulation cost is exponential in the entanglement contained in a certain
effective state, capturing the encoded state, the encoding and the local
post-measurement states. The same efficiencies hold, with additional
assumptions on the temporal order of measurements and on the tessellations of
the code surfaces, for the harder task of sampling from the distribution of the
computational output.Comment: 21 pages, 13 figure
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Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study
Aims
To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function.
Methods
An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity.
Results
After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively.
Conclusions
Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction
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