Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming

BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. METHODS and RESULTS: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. CONCLUSIONS: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT

Charge Ordering in the One-Dimensional Extended Hubbard Model: Implication to the TMTTF Family of Organic Conductors

We study the charge ordering (CO) in the one-dimensional (1D) extended Hubbard model at quarter filling where the nearest-neighbor Coulomb repulsion and dimerization in the hopping parameters are included. Using the cluster mean-field approximation to take into account the effect of quantum fluctuations, we determine the CO phase boundary of the model in the parameter space at T=0 K. We thus find that the dimerization suppresses the stability of the CO phase strongly, and in consequence, the realistic parameter values for quasi-1D organic materials such as (TMTTF)$_2$PF$_6$ are outside the region of CO. We suggest that the long-range Coulomb interaction between the chains should persist to stabilize the CO phase.Comment: 5 pages, 4 eps figures, to appear in 15 Nov. 2001 issue of PR

Nonmyeloablative Peripheral Blood Haploidentical Stem Cell Transplantation for Refractory Severe Aplastic Anemia

New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy

Topological reversibility and causality in feed-forward networks

Systems whose organization displays causal asymmetry constraints, from evolutionary trees to river basins or transport networks, can be often described in terms of directed paths (causal flows) on a discrete state space. Such a set of paths defines a feed-forward, acyclic network. A key problem associated with these systems involves characterizing their intrinsic degree of path reversibility: given an end node in the graph, what is the uncertainty of recovering the process backwards until the origin? Here we propose a novel concept, \textit{topological reversibility}, which rigorously weigths such uncertainty in path dependency quantified as the minimum amount of information required to successfully revert a causal path. Within the proposed framework we also analytically characterize limit cases for both topologically reversible and maximally entropic structures. The relevance of these measures within the context of evolutionary dynamics is highlighted.Comment: 9 pages, 3 figure

Tricritical Behavior in the Extended Hubbard Chains

Phase diagrams of the one-dimensional extended Hubbard model (including nearest-neighbor interaction $V$) at half- and quarter-filling are studied by observing level crossings of excitation spectra using the exact diagonalization. This method is based on the Tomonaga-Luttinger liquid theory including logarithmic corrections which stem from the renormalization of the Umklapp- and the backward-scattering effects. Using this approach, the phase boundaries are determined with high accuracy, and then the structure of the phase diagram is clarified. At half-filling, the phase diagram consists of two Berezinskii-Kosterlitz-Thouless (BKT) transition lines and one Gaussian transition line in the charge sector, and one spin-gap transition line. This structure reflects the U(1) $\otimes$ SU(2) symmetry of the electron system. Near the $U=2V$ line, the Gaussian and the spin-gap transitions take place independently from the weak- to the intermediate-coupling region, but these two transition lines are coupled in the strong-coupling region. This result demonstrates existence of a tricritical point and a bond-charge-density-wave (BCDW) phase between charge- and spin-density-wave (CDW, SDW) phases. To clarify this mechanism of the transition, we also investigate effect of a correlated hopping term which plays a role to enlarge BCDW and bond-spin-density-wave (BSDW) phases. At quarter-filling, a similar crossover phenomenon also takes place in the large-$V$ region involving spin-gap and BKT-type metal-insulator transitions.Comment: 18 pages(REVTeX), 17 figures(EPS(color)), 3 tables, Detailed paper of JPSJ 68 (1999) 3123 (cond-mat/9903227), see also cond-mat/000341

Propagation of ultra-high energy protons in the nearby universe

We present a new calculation of the propagation of protons with energies above $10^{19}$ eV over distances of up to several hundred Mpc. The calculation is based on a Monte Carlo approach using the event generator SOPHIA for the simulation of hadronic nucleon-photon interactions and a realistic integration of the particle trajectories in a random extragalactic magnetic field. Accounting for the proton scattering in the magnetic field affects noticeably the nucleon energy as a function of the distance to their source and allows us to give realistic predictions on arrival energy, time delay, and arrival angle distributions and correlations as well as secondary particle production spectra.Comment: 12 pages, 9 figures, ReVTeX. Physical Review D, accepte

Bond and charge density waves in the isotropic interacting two-dimensional quarter-filled band and the insulating state proximate to organic superconductivity

We report two surprising results regarding the nature of the spatial broken symmetries in the two-dimensional (2D), quarter-filled band with strong electron-electron interactions. First, in direct contradiction to the predictions of one-electron theory, we find a coexisting ``bond-order and charge density wave'' (BCDW) insulating ground state in the 2D rectangular lattice for all anisotropies, including the isotropic limit. Second, we find that the BCDW further coexists with a spin-density wave (SDW) in the range of large anisotropy. Further, in contrast to the interacting half-filled band, in the interacting quarter-filled band there are two transitions: first, a similar singlet-to-AFM/SDW transition for large anisotropy and second, an AFM/SDW-to-singlet transition at smaller anisotropy. We discuss how these theoretical results apply to the insulating states that are proximate to the superconducting states of 2:1 cationic charge-transfer solids (CTS). An important consequence of this work is the suggestion that organic superconductivity is related to the proximate Coulomb-induced BCDW, with the SDW that coexists for large anisotropies being also a consequence of the BCDW, rather than the driver of superconductivity.Comment: 29 pages, 18 eps figures. Revised with new appendices; to appear in Phys. Rev. B 62, Nov 15, 200

Ultrahigh Energy Cosmic Rays: The state of the art before the Auger Observatory

In this review we discuss the important progress made in recent years towards understanding the experimental data on cosmic rays with energies \agt 10^{19} eV. We begin with a brief survey of the available data, including a description of the energy spectrum, mass composition, and arrival directions. At this point we also give a short overview of experimental techniques. After that, we introduce the fundamentals of acceleration and propagation in order to discuss the conjectured nearby cosmic ray sources. We then turn to theoretical notions of physics beyond the Standard Model where we consider both exotic primaries and exotic physical laws. Particular attention is given to the role that TeV-scale gravity could play in addressing the origin of the highest energy cosmic rays. In the final part of the review we discuss the potential of future cosmic ray experiments for the discovery of tiny black holes that should be produced in the Earth's atmosphere if TeV-scale gravity is realized in Nature.Comment: Final version. To be published in Int. J. Mod. Phys.

Subset currents on free groups

We introduce and study the space of \emph{subset currents} on the free group $F_N$. A subset current on $F_N$ is a positive $F_N$-invariant locally finite Borel measure on the space $\mathfrak C_N$ of all closed subsets of $\partial F_N$ consisting of at least two points. While ordinary geodesic currents generalize conjugacy classes of nontrivial group elements, a subset current is a measure-theoretic generalization of the conjugacy class of a nontrivial finitely generated subgroup in $F_N$, and, more generally, in a word-hyperbolic group. The concept of a subset current is related to the notion of an "invariant random subgroup" with respect to some conjugacy-invariant probability measure on the space of closed subgroups of a topological group. If we fix a free basis $A$ of $F_N$, a subset current may also be viewed as an $F_N$-invariant measure on a "branching" analog of the geodesic flow space for $F_N$, whose elements are infinite subtrees (rather than just geodesic lines) of the Cayley graph of $F_N$ with respect to $A$.Comment: updated version; to appear in Geometriae Dedicat