Beyond A-Theory and the Block Universe: A non-circular derivation of “before”, change, and local asymmetric time

This article proposes a “third way” in the philosophy of time beyond A-theory and the block universe, in which time is understood as a purely local phenomenon. It does so by starting with simple metaphysical assumptions about substances and their properties. Based on these assumptions, the notions of “before”, of change, and of time as a local quantification of change can be derived non-circularly, i.e. without invoking temporal concepts. I then proceed to prove the irreversibility of local time by showing that the propositional content of the local past cannot be changed, since this would imply a contradiction, whereas that of the future can. Time’s familiar asymmetric character, in particular the difference between the fixed past and the open or “branching” future, is therefore a non-illusory but purely local phenomenon. Such a model requires no past-present-future distinction valid for the entire cosmos, and is therefore consistent with special and general relativity. The article furthermore explores the implications of this model for the notion of an evolving universe

Beyond A-Theory and the Block Universe: A non-circular derivation of “before”, change, and the local arrow of time

This article proposes a “third way” in the philosophy of time beyond A-theory and the block universe, in which time is understood as a purely local phenomenon. It does so by starting with simple metaphysical assumptions about substances and their properties. Based on these assumptions, the notions of “before”, of change, and of time as local quantification of change can be derived non-circularly, i.e. without invoking temporal concepts. I then proceed to prove the irreversibility of local time by showing that the propositional content of the local past cannot be changed, since this would imply a contradiction, whereas that of the future can. Time’s familiar asymmetric character, in particular the difference between the fixed past and the open or “branching” future, is therefore a non-illusory but purely local phenomenon. Such a model requires no past-present-future distinction valid for the entire cosmos, and is therefore consistent with special and general relativity

Beyond A-Theory and the Block Universe: A non-circular derivation of “before”, change, and local asymmetric time

This article proposes a “third way” in the philosophy of time beyond A-theory and the block universe, in which time is understood as a purely local phenomenon. It does so by starting with simple metaphysical assumptions about substances and their properties. Based on these assumptions, the notions of “before”, of change, and of time as a local quantification of change can be derived non-circularly, i.e. without invoking temporal concepts. I then proceed to prove the irreversibility of local time by showing that the propositional content of the local past cannot be changed, since this would imply a contradiction, whereas that of the future can. Time’s familiar asymmetric character, in particular the difference between the fixed past and the open or “branching” future, is therefore a non-illusory but purely local phenomenon. Such a model requires no past-present-future distinction valid for the entire cosmos, and is therefore consistent with special and general relativity. The article furthermore explores the implications of this model for the notion of an evolving universe

Beyond A-Theory and the Block Universe: A non-circular derivation of “before”, change, and the local arrow of time

This article proposes a “third way” in the philosophy of time beyond A-theory and the block universe, in which time is understood as a purely local phenomenon. It does so by starting with simple metaphysical assumptions about substances and their properties. Based on these assumptions, the notions of “before”, of change, and of time as local quantification of change can be derived non-circularly, i.e. without invoking temporal concepts. I then proceed to prove the irreversibility of local time by showing that the propositional content of the local past cannot be changed, since this would imply a contradiction, whereas that of the future can. Time’s familiar asymmetric character, in particular the difference between the fixed past and the open or “branching” future, is therefore a non-illusory but purely local phenomenon. Such a model requires no past-present-future distinction valid for the entire cosmos, and is therefore consistent with special and general relativity

The structure and properties of horse muscle acylphosphatase in solution Mobility of antigenic and active site regions

AbstractThe solution structure of acylphosphatase determined by proton nuclear magnetic resonance spectroscopy is described. The results allow us to discuss the fold of the protein (101 amino acids), to correlate the exposure and the mobility of the backbone with the antigenicity, and to locate the active site

GDF15: A Hormone Conveying Somatic Distress to the Brain.

GDF15 has recently gained scientific and translational prominence with the discovery that its receptor is a GFRAL-RET heterodimer of which GFRAL is expressed solely in the hindbrain. Activation of this receptor results in reduced food intake and loss of body weight and is perceived and recalled by animals as aversive. This information encourages a revised interpretation of the large body of previous research on the protein. GDF15 can be secreted by a wide variety of cell types in response to a broad range of stressors. We propose that central sensing of GDF15 via GFRAL-RET activation results in behaviors that facilitate the reduction of exposure to a noxious stimulus. The human trophoblast appears to have hijacked this signal, producing large amounts of GDF15 from early pregnancy. We speculate that this encourages avoidance of potential teratogens in pregnancy. Circulating GDF15 levels are elevated in a range of human disease states, including various forms of cachexia, and GDF15-GFRAL antagonism is emerging as a therapeutic strategy for anorexia/cachexia syndromes. Metformin elevates circulating GDF15 chronically in humans and the weight loss caused by this drug appears to be dependent on the rise in GDF15. This supports the concept that chronic activation of the GDF15-GFRAL axis has efficacy as an antiobesity agent. In this review, we examine the science of GDF15 since its identification in 1997 with our interpretation of this body of work now being assisted by a clear understanding of its highly selective central site of action

Site-Specific GlcNAcylation of Human Erythrocyte Proteins: Potential Biomarker(s) for Diabetes

OBJECTIVE—O-linked N-acetylglucosamine (O-GlcNAc) is upregulated in diabetic tissues and plays a role in insulin resistance and glucose toxicity. Here, we investigated the extent of GlcNAcylation on human erythrocyte proteins and compared site-specific GlcNAcylation on erythrocyte proteins from diabetic and normal individuals

Comparison of a point-of-care analyser for the determination of HbA1c with HPLC method

As the use of Point of Care Testing (POCT) devices for measurement of glycated haemoglobin (HbA1c) increases, it is imperative to determine how their performance compares to laboratory methods. This study compared the performance of the automated Quo-Test POCT device (EKF Diagnostics), which uses boronate fluorescence quenching technology, with a laboratory based High Performance Liquid Chromatography (HPLC) method (Biorad D10) for measurement of HbA1c.MethodsWhole blood EDTA samples from subjects (n=100) with and without diabetes were assayed using a BioRad D10 and a Quo-Test analyser. Intra-assay variation was determined by measuring six HbA1c samples in triplicate and inter-assay variation was determined by assaying four samples on 4 days. Stability was determined by assaying three samples stored at −20 °C for 14 and 28 days post collection.ResultsMedian (IQR) HbA1c was 60 (44.0–71.2) mmol/mol (7.6 (6.17–8.66) %) and 62 (45.0–69.0) mmol/mol (7.8 (6.27–8.46) %) for D10 and Quo-Test, respectively, with very good agreement (R2=0.969, P<0.0001). Mean (range) intra- and inter-assay variation was 1.2% (0.0–2.7%) and 1.6% (0.0–2.7%) for the D10 and 3.5% (0.0–6.7%) and 2.7% (0.7–5.1%) for the Quo-Test. Mean change in HbA1c after 28 days storage at −20 °C was −0.7% and +0.3% for D10 and Quo-Test respectively. Compared to the D10, Quo-Test showed 98% agreement for diagnosis of glucose intolerance (IGT and T2DM) and 100% for diagnosis of T2DM.ConclusionGood agreement between the D10 and Quo-Test was seen across a wide HbA1c range. The Quo-Test POCT device provided similar performance to a laboratory based HPLC method