Multi-PeV Signals from a New Astrophysical Neutrino Flux Beyond the Glashow Resonance

The IceCube neutrino discovery was punctuated by three showers with $E_\nu$ ~ 1-2 PeV. Interest is intense in possible fluxes at higher energies, though a marked deficit of $E_\nu$ ~ 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 $\pm$ 0.3 PeV. A muon depositing so much energy can imply $E_{\nu_\mu} \gtrsim$ 10 PeV. We show that extending the soft $E_\nu^{-2.6}$ spectral fit from TeV-PeV data is unlikely to yield such an event. Alternatively, a tau can deposit this much energy, though requiring $E_{\nu_\tau}$ ~10x higher. We find that either scenario hints at a new flux, with the hierarchy of $\nu_\mu$ and $\nu_\tau$ energies suggesting a window into astrophysical neutrinos at $E_\nu$ ~ 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

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 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

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