2,188 research outputs found
Multi-PeV Signals from a New Astrophysical Neutrino Flux Beyond the Glashow Resonance
The IceCube neutrino discovery was punctuated by three showers with ~
1-2 PeV. Interest is intense in possible fluxes at higher energies, though a
marked deficit of ~ 6 PeV Glashow resonance events implies a spectrum
that is soft and/or cutoff below ~few PeV. However, IceCube recently reported a
through-going track event depositing 2.6 0.3 PeV. A muon depositing so
much energy can imply 10 PeV. We show that extending the
soft spectral fit from TeV-PeV data is unlikely to yield such an
event. Alternatively, a tau can deposit this much energy, though requiring
~10x higher. We find that either scenario hints at a new flux,
with the hierarchy of and energies suggesting a window
into astrophysical neutrinos at ~ 100 PeV if a tau. We address
implications, including for ultrahigh-energy cosmic-ray and neutrino origins.Comment: 6 pages, 4 figures + 3 pages Supplementary Material; updated to agree
with version published in Physical Review Letter
Inositol phosphate kinases in the eukaryote landscape
Inositol phosphate encompasses a large multifaceted family of signalling molecules that originate from the combinatorial attachment of phosphate groups to the inositol ring. To date, four distinct inositol kinases have been identified, namely, IPK, ITPK, IPPK (IP5-2K), and PPIP5K. Although, ITPKs have recently been identified in archaea, eukaryotes have taken advantage of these enzymes to create a sophisticated signalling network based on inositol phosphates. However, it remains largely elusive what fundamental biochemical principles control the signalling cascade. Here, we present an evolutionary approach to understand the development of the 'inositol phosphate code' in eukaryotes. Distribution analyses of these four inositol kinase groups throughout the eukaryotic landscape reveal the loss of either ITPK, or of PPIP5K proteins in several species. Surprisingly, the loss of IPPK, an enzyme thought to catalyse the rate limiting step of IP6 (phytic acid) synthesis, was also recorded. Furthermore, this study highlights a noteworthy difference between animal (metazoan) and plant (archaeplastida) lineages. While metazoan appears to have a substantial amplification of IPK enzymes, archaeplastida genomes show a considerable increase in ITPK members. Differential evolution of IPK and ITPK between plant and animal lineage is likely reflective of converging functional adaptation of these two types of inositol kinases. Since, the IPK family comprises three sub-types IPMK, IP6K, and IP3-3K each with dedicated enzymatic specificity in metazoan, we propose that the amplified ITPK group in plant could be classified in sub-types with distinct enzymology
A sticky business: the status of the conjectured viscosity/entropy density bound
There have been a number of forms of a conjecture that there is a universal
lower bound on the ratio, eta/s, of the shear viscosity, eta, to entropy
density, s, with several different domains of validity. We examine the various
forms of the conjecture. We argue that a number of variants of the conjecture
are not viable due to the existence of theoretically consistent
counterexamples. We also note that much of the evidence in favor of a bound
does not apply to the variants which have not yet been ruled out.Comment: 23 pages, 4 figures, added references, corrected typos, added
subsection in response to Son's comments in arXiv:0709.465
ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism
Inositol phosphates (IPs) comprise a network of phosphorylated molecules that play multiple signaling roles in eukaryotes. IPs synthesis is believed to originate with IP_{3} generated from PIP_{2} by phospholipase C (PLC). Here, we report that in mammalian cells PLC-generated IPs are rapidly recycled to inositol, and uncover the enzymology behind an alternative “soluble” route to synthesis of IPs. Inositol tetrakisphosphate 1-kinase 1 (ITPK1)—found in Asgard archaea, social amoeba, plants, and animals—phosphorylates I(3)P_{1} originating from glucose-6-phosphate, and I(1)P_{1} generated from sphingolipids, to enable synthesis of IP_{6}. We also found using PAGE mass assay that metabolic blockage by phosphate starvation surprisingly increased IP_{6} levels in a ITPK1-dependent manner, establishing a route to IP_{6} controlled by cellular metabolic status, that is not detectable by traditional [{3}^H]-inositol labeling. The presence of ITPK1 in archaeal clades thought to define eukaryogenesis indicates that IPs had functional roles before the appearance of the eukaryote
Galactic Center Radio Constraints on Gamma-Ray Lines from Dark Matter Annihilation
Recent evidence for one or more gamma-ray lines at ~ 130 GeV in the Fermi-LAT
data from the Galactic Center has been interpreted as a hint for dark matter
annihilation to Z{\gamma} or H{\gamma} with an annihilation cross section,
~ 10^{-27} cm^3 s^{-1} . We test this hypothesis by comparing
synchrotron fluxes due to the electrons and positrons from the decay of the Z
or the H boson only in the Galactic Center against radio data from the same
region in the Galactic Center. We find that the radio data from single dish
telescopes marginally constrain this interpretation of the claimed gamma lines
for a contracted NFW profile. Already-operational radio telescopes such as LWA,
VLA-Low and LOFAR, and future radio telescopes like SKA, which are sensitive to
annihilation cross sections as small as 10^{-28} cm^3 s^{-1}, can confirm or
rule out this scenario very soon. We discuss the assumptions on the dark matter
profile, magnetic fields, and background radiation density profiles, and show
that the constraints are relatively robust for any reasonable assumptions.
Independent of the above said recent developments, we emphasize that our radio
constraints apply to all models where dark matter annihilates to Z{\gamma} or
H{\gamma}.Comment: v3: 18 pages, 7 figures. Minor changes. Published in Phys. Rev.
ITPK1 is an InsP6/ADP phosphotransferase that controls phosphate signaling in Arabidopsis
In plants, phosphate (Pi) homeostasis is regulated by the interaction of PHR transcription factors with stand-alone SPX proteins, which act as sensors for inositol pyrophosphates. Here, we combined different methods to obtain a comprehensive picture of how inositol (pyro)phosphate metabolism is regulated by Pi and dependent on the inositol phosphate kinase ITPK1. We found that inositol pyrophosphates are more responsive to Pi than lower inositol phosphates, a response conserved across kingdoms. With CE-ESI-MS we could separate different InsP7 isomers in Arabidopsis and rice, and identify 4/6-InsP7 and a PP-InsP4 isomer hitherto not reported in plants. We found that the inositol pyrophosphates 1/3-InsP7, 5-InsP7 and InsP8 increase severalfold in shoots after Pi resupply and that tissue-specific accumulation of inositol pyrophosphates relies on ITPK1 activities and MRP5-dependent InsP6 compartmentalization. Notably, ITPK1 is critical for Pi-dependent 5-InsP7 and InsP8 synthesis in planta and its activity regulates Pi starvation responses in a PHR-dependent manner. Furthermore, we demonstrate that ITPK1-mediated conversion of InsP6 to 5-InsP7 requires high ATP concentrations and that Arabidopsis ITPK1 has an ADP phosphotransferase activity to dephosphorylate specifically 5-InsP7 under low ATP. Collectively, our study provides deeper insights into Pi-dependent changes in nutritional and energetic states with the synthesis of regulatory inositol pyrophosphates
Free Meixner states
Free Meixner states are a class of functionals on non-commutative polynomials
introduced in math.CO/0410482. They are characterized by a resolvent-type form
for the generating function of their orthogonal polynomials, by a recursion
relation for those polynomials, or by a second-order non-commutative
differential equation satisfied by their free cumulant functional. In this
paper, we construct an operator model for free Meixner states. By combinatorial
methods, we also derive an operator model for their free cumulant functionals.
This, in turn, allows us to construct a number of examples. Many of these
examples are shown to be trivial, in the sense of being free products of
functionals which depend on only a single variable, or rotations of such free
products. On the other hand, the multinomial distribution is a free Meixner
state and is not a product. Neither is a large class of tracial free Meixner
states which are analogous to the simple quadratic exponential families in
statistics.Comment: 30 page
Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors
Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer’s disease. A structure–activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved
Arabidopsis ITPK1 and ITPK2 Have an Evolutionarily Conserved Phytic Acid Kinase Activity
Diphospho-myo-inositol polyphosphates, also termed inositol pyrophosphates, are molecular messengers containing at least one high-energy phosphoanhydride bond and regulate a wide range of cellular processes in eukaryotes. While inositol pyrophosphates InsP7 and InsP8 are present in different plant species, both the identity of enzymes responsible for InsP7 synthesis and the isomer identity of plant InsP7 remain unknown. This study demonstrates that Arabidopsis ITPK1 and ITPK2 catalyze the phosphorylation of phytic acid (InsP6) to the symmetric InsP7 isomer 5-InsP7 and that the InsP6 kinase activity of ITPK enzymes is evolutionarily conserved from humans to plants. We also show by 31P nuclear magnetic resonance that plant InsP7 is structurally identical to the in vitro InsP6 kinase products of ITPK1 and ITPK2. Our findings lay the biochemical and genetic basis for uncovering physiological processes regulated by 5-InsP7 in plants
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