451 research outputs found
Leibniz, Acosmism, and Incompossibility
Leibniz claims that God acts in the best possible way, and that this includes creating exactly one world. But worlds are aggregates, and aggregates have a low degree of reality or metaphysical perfection, perhaps none at all. This is Leibnizâs tendency toward acosmism, or the view that there this no such thing as creation-as-a-whole. Many interpreters reconcile Leibnizâs acosmist tendency with the high value of worlds by proposing that God sums the value of each substance created, so that the best world is just the world with the most substances. I call this way of determining the value of a world the Additive Theory of Value (ATV), and argue that it leads to the current and insoluble form of the problem of incompossibility. To avoid the problem, I read âpossible worldsâ in âGod chooses the best of all possible worldsâ as referring to Godâs ideas of worlds. These ideas, though built up from essences, are themselves unities and so well suited to be the value bearers that Leibnizâs theodicy requires. They have their own value, thanks to their unity, and that unity is not preserved when more essences are added
Network of Earthquakes and Recurrences Therein
We quantify the correlation between earthquakes and use the same to
distinguish between relevant causally connected earthquakes. Our correlation
metric is a variation on the one introduced by Baiesi and Paczuski (2004). A
network of earthquakes is constructed, which is time ordered and with links
between the more correlated ones. Data pertaining to the California region has
been used in the study. Recurrences to earthquakes are identified employing
correlation thresholds to demarcate the most meaningful ones in each cluster.
The distribution of recurrence lengths and recurrence times are analyzed
subsequently to extract information about the complex dynamics. We find that
the unimodal feature of recurrence lengths helps to associate typical rupture
lengths with different magnitude earthquakes. The out-degree of the network
shows a hub structure rooted on the large magnitude earthquakes. In-degree
distribution is seen to be dependent on the density of events in the
neighborhood. Power laws are also obtained with recurrence time distribution
agreeing with the Omori law.Comment: 17 pages, 5 figure
E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia
Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S.aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S.aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S.aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. Š 2014 The Authors
Effect of the Sumatran mega-earthquake on the global magnitude cut-off and event rate:Correspondence
Flavor SU(3) symmetry and QCD factorization in and decays
Using flavor SU(3) symmetry, we perform a model-independent analysis of
charmless decays. All the relevant
topological diagrams, including the presumably subleading diagrams, such as the
QCD- and EW-penguin exchange diagrams and flavor-singlet weak annihilation
ones, are introduced. Indeed, the QCD-penguin exchange diagram turns out to be
important in understanding the data for penguin-dominated decay modes. In this
work we make efforts to bridge the (model-independent but less quantitative)
topological diagram or flavor SU(3) approach and the (quantitative but somewhat
model-dependent) QCD factorization (QCDF) approach in these decays, by
explicitly showing how to translate each flavor SU(3) amplitude into the
corresponding terms in the QCDF framework. After estimating each flavor SU(3)
amplitude numerically using QCDF, we discuss various physical consequences,
including SU(3) breaking effects and some useful SU(3) relations among decay
amplitudes of and .Comment: 47 pages, 3 figures, 28 table
Anomalous coupling effects in exclusive radiative B-meson decays
The top-quark FCNC processes will be searched for at the CERN LHC, which are
correlated with the B-meson decays. In this paper, we study the effects of
top-quark anomalous interactions in the exclusive radiative and decays. With the current experimental data of
the branching ratios, the direct CP and the isospin asymmetries, bounds on the
coupling from and
from decays are derived,
respectively. The bound on from is generally compatible with that from . However, the isospin asymmetry further
restrict the phase of , and the combined bound results
in the upper limit, , which is lower than the
CDF result. For real , the upper bound on is about of the same order as the discovery
potential of ATLAS with an integrated luminosity of . For
decays, the NP contribution is enhanced by a large CKM factor
, and the constraint on coupling is rather
restrictive, . With refined
measurements to be available at the LHCb and the future super-B factories, we
can get close correlations between and the rare
decays, which will be studied directly at the LHC ATLAS and CMS.Comment: 25 pages, 15 figures, pdflate
Phospholipase iPLA2β averts ferroptosis by eliminating a redox lipid death signal
Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca^{2+} -independent phospholipase A2β (iPLA2β, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA_{2}β averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinsonâs disease (PD)-associated mutation (fPD^{R747W}) and found selectively decreased 15-HpETE-PE-hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-Cas9-engineered Pnpla9^{R748W/R748W} mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and Îą-synuclein-mutant Snca^{A53T} mice, with decreased iPLA2β expression and a PD-relevant phenotype. Thus, iPLA_{2}β is a new ferroptosis regulator, and its mutations may be implicated in PD pathogenesis
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