Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment

Dripping Faucet Dynamics Clarified by an Improved Mass-Spring Model

An improved mass-spring model for a dripping faucet is presented. The model is constructed based on the numerical results which we recently obtained from fluid dynamical calculations. Both the fluid dynamical calculations and the present mass-spring model exhibit a variety of complex behavior including transition to chaos in good agreement with experiments. Further, the mass-spring model reveals fundamental dynamics inherent in the dripping faucet system.Comment: 17 pages, 17 figure

Treatment of giant congenital melanocytic nevi with cultured epithelial autografts: Clinical and histopathological analysis

[Introduction] Curettage and dermabrasion are effective in the treatment of giant congenital melanocytic nevi (GCMN); however, local infection and hypertrophic scar formation are major issues. Thus, we applied cultured epithelial autografts (CEA) on skin defects after curettage or abrasion of GCMN and assessed the postoperative outcomes. [Methods] Seven nevi lesions of five patients (aged 3 months to 24 years) were treated with CEA after curettage or abrasion with a dermatome or a surgical bar, respectively. We assessed the postoperative outcomes, including CEA take ratio, erosion and/or ulcer formation in the acute phase, hospitalization days, Vancouver scar scale, and color improvement one year after the operation. In addition, a histological evaluation of a skin biopsy was performed over one year after the operation. [Results] The CEAs took well on the wound, and the wound surface was mostly epithelized by postoperative day 7 in all cases. While hypertrophic scar formation and slight pigmentation were observed in some lesions, the color was improved in all of the treated lesions. Histopathological examination revealed that the regenerated epidermis had stratified keratinocytes with rete ridges, and the dermal layer without nevus cells regenerated above the remaining dermis layer. [Conclusions] In this study, we found that early epithelialization and regeneration of the dermal layer was achieved after the application of CEA, suggesting that CEA could be an effective option after curettage or abrasion of GCMN

Crystallization of authigenic carbonates in mud volcanoes at Lake Baikal

This paper presents data on authigenic siderite first found in surface sediments from mud volcanoes in the Central (K-2) and Southern (Malen’kii) basins of Lake Baikal. Ca is the predominant cation, which substitutes Fe in the crystalline lattice of siderite. The enrichment of the carbonates in the 13C isotope (from +3.3 to +6.8‰ for the Malen’kii volcano and from +17.7 to +21.9‰ for K-2) results from the crystallization of the carbonates during methane generation via the bacterial destruction of organic matter (acetate). The overall depletion of the carbonates in 18O is mainly inherited from the isotopic composition of Baikal water

Thermodynamics of the (1,1/2) Ferrimagnet in Finite Magnetic Fields

We investigate the specific heat and magnetisation of a ferrimagnet with gS=1 and S=1/2 spins in a finite magnetic field using the transfer matrix DMRG down to T=0.025J. Ferromagnetic gapless and antiferromagnetic gapped excitations for H=0 lead to rich thermodynamics for H > 0. While the specific heat is characterized by a generic double peak structure, magnetisation reveals two critical fields, Hc1=1.76(1) and Hc2=3.00(1) with square-root behaviour in the T=0 magnetisation. Simple analytical arguments allow to understand these experimentally accessible findings.Comment: 5 pages, 7 eps figures, uses RevTeX, submitted to PR

Elementary Excitations of Heisenberg Ferrimagnetic Spin Chains

We numerically investigate elementary excitations of the Heisenberg alternating-spin chains with two kinds of spins 1 and 1/2 antiferromagnetically coupled to each other. Employing a recently developed efficient Monte Carlo technique as well as an exact diagonalization method, we verify the spin-wave argument that the model exhibits two distinct excitations from the ground state which are gapless and gapped. The gapless branch shows a quadratic dispersion in the small-momentum region, which is of ferromagnetic type. With the intention of elucidating the physical mechanism of both excitations, we make a perturbation approach from the decoupled-dimer limit. The gapless branch is directly related to spin 1's, while the gapped branch originates from cooperation of the two kinds of spins.Comment: 7 pages, 7 Postscript figures, RevTe

Statics, metastable states and barriers in protein folding: A replica variational approach

Protein folding is analyzed using a replica variational formalism to investigate some free energy landscape characteristics relevant for dynamics. A random contact interaction model that satisfies the minimum frustration principle is used to describe the coil-globule transition (characterized by T_CG), glass transitions (by T_A and T_K) and folding transition (by T_F). Trapping on the free energy landscape is characterized by two characteristic temperatures, one dynamic, T_A the other static, T_K (T_A> T_K), which are similar to those found in mean field theories of the Potts glass. 1)Above T_A, the free energy landscape is monotonous and polymer is melted both dynamically and statically. 2)Between T_A and T_K, the melted phase is still dominant thermodynamically, but frozen metastable states, exponentially large in number, appear. 3)A few lowest minima become thermodynamically dominant below T_K, where the polymer is totally frozen. In the temperature range between T_A and T_K, barriers between metastable states are shown to grow with decreasing temperature suggesting super-Arrhenius behavior in a sufficiently large system. Due to evolutionary constraints on fast folding, the folding temperature T_F is expected to be higher than T_K, but may or may not be higher than T_A. Diverse scenarios of the folding kinetics are discussed based on phase diagrams that take into account the dynamical transition, as well as the static ones.Comment: 41 pages, LaTeX, 9 EPS figure

Dark Matter Model Selection and the ATIC/PPB-BETS anomaly

We argue that we may be able to sort out dark matter models in which electrons are generated through the annihilation and/or decay of dark matter, by using a fact that the initial energy spectrum is reflected in the cosmic-ray electron flux observed at the Earth even after propagation through the galactic magnetic field. To illustrate our idea we focus on three representative initial spectra: (i)monochromatic (ii)flat and (iii)double-peak ones. We find that those three cases result in significantly different energy spectra, which may be probed by the Fermi satellite in operation or an up-coming cosmic-ray detector such as CALET.Comment: 19 pages, 8 figure

Self-trapping and stable localized modes in nonlinear photonic crystals

We predict the existence of stable nonlinear localized modes near the band edge of a two-dimensional reduced-symmetry photonic crystal with a Kerr nonlinearity. Employing the technique based on the Green function, we reveal a physical mechanism of the mode stabilization associated with the effective nonlinear dispersion and long-range interaction in the photonic crystals.Comment: 4 pages (RevTex) with 5 figures (EPS

Magnetic Properties of Quantum Ferrimagnetic Spin Chains

Magnetic susceptibilities of spin-$(S,s)$ ferrimagnetic Heisenberg chains are numerically investigated. It is argued how the ferromagnetic and antiferromagnetic features of quantum ferrimagnets are exhibited as functions of $(S,s)$. Spin-$(S,s)$ ferrimagnetic chains behave like combinations of spin-$(S-s)$ ferromagnetic and spin-$(2s)$ antiferromagnetic chains provided $S=2s$.Comment: 4 pages, 7 PS figures, to appear in Phys. Rev. B: Rapid Commu