Human monoclonal islet specific autoantibodies share features of islet cell and 64 kDa antibodies

The first human monoclonal islet cell antibodies of the IgG class (MICA 1-6) obtained from an individual with Type 1 (insulin-dependent) diabetes mellitus were cytoplasmic islet cell antibodies selected by the indirect immunofluorescence test on pancreas sections. Surprisingly, they all recognized the 64 kDa autoantigen glutamate decarboxylase. In this study we investigated which typical features of cytoplasmic islet cell antibodies are represented by these monoclonals. We show by double immunofluorescence testing that MICA 1-6 stain pancreatic beta cells which is in agreement with the beta-cell specific expression of glutamate decarboxylase. In contrast an islet-reactive IgM monoclonal antibody obtained from a pre-diabetic individual stained all islet cells but lacked the tissue specificity of MICA 1-6 and must therefore be considered as a polyreactive IgM-antibody. We further demonstrate that MICA 1-6 revealed typical features of epitope sensitivity to biochemical treatment of the target tissue which has been demonstrated for islet cell antibodies, and which has been used to argue for a lipid rather than a protein nature of target antigens. Our results provide direct evidence that the epitopes recognized by the MICA are destroyed by methanol/chloroform treatment but reveal a high stability to Pronase digestion compared to proinsulin epitopes. Conformational protein epitopes in glutamate decarboxylase therefore show a sensitivity to biochemical treatment of sections such as ganglioside epitopes. MICA 1-6 share typical features of islet cell and 64 kDa antibodies and reveal that glutamate decarboxylase-reactive islet cell antibodies represent a subgroup of islet cell antibodies present in islet cell antibody-positive sera

Disease Surveillance Networks Initiative Asia: Final Evaluation

The DSN Initiative was launched in 2007 under the new strategy of the Rockefeller Foundation. The initiative intends:[1] To improve human resources for disease surveillance in developing countries, thus bolstering national capacity to monitor, report, and respond to outbreaks;[2] To support regional networks to promote collaboration in disease surveillance and response across countries; and[3] To build bridges between regional and global monitoring effortsThe purpose of the DSN evaluation in the Mekong region was twofold:[1]To inform the work and strategy of the Foundation, its grantees, and the broader field of disease surveillance, based on the experience of DSN investments in the Mekong region. More specifically, the evaluation will inform future directions and strategies for current areas of DSN Initiative work, particularly in Asia, and will highlight potential new areas of work and strategy; and[2] To provide accountability to the Rockefeller Foundation's board, staff, and stakeholders for the DSN funds spent in the Mekong region

Effect of anisotropy on the ground-state magnetic ordering of the spin-one quantum J1XXZJ_{1}^{XXZ}--J2XXZJ_{2}^{XXZ} model on the square lattice

We study the zero-temperature phase diagram of the $J_{1}^{XXZ}$--$J_{2}^{XXZ}$ Heisenberg model for spin-1 particles on an infinite square lattice interacting via nearest-neighbour ($J_1 \equiv 1$) and next-nearest-neighbour ($J_2 > 0$) bonds. Both bonds have the same $XXZ$-type anisotropy in spin space. The effects on the quasiclassical N\'{e}el-ordered and collinear stripe-ordered states of varying the anisotropy parameter $\Delta$ is investigated using the coupled cluster method carried out to high orders. By contrast with the spin-1/2 case studied previously, we predict no intermediate disordered phase between the N\'{e}el and collinear stripe phases, for any value of the frustration $J_2/J_1$, for either the $z$-aligned ($\Delta > 1$) or $xy$-planar-aligned ($0 \leq \Delta < 1$) states. The quantum phase transition is determined to be first-order for all values of $J_2/J_1$ and $\Delta$. The position of the phase boundary $J_{2}^{c}(\Delta)$ is determined accurately. It is observed to deviate most from its classical position $J_2^c = {1/2}$ (for all values of $\Delta > 0$) at the Heisenberg isotropic point ($\Delta = 1$), where $J_{2}^{c}(1) = 0.55 \pm 0.01$. By contrast, at the XY isotropic point ($\Delta = 0$), we find $J_{2}^{c}(0) = 0.50 \pm 0.01$. In the Ising limit ($\Delta \to \infty$) $J_2^c \to 0.5$ as expected.Comment: 20 pages, 5 figure

Signatures of partition functions and their complexity reduction through the KP II equation

A statistical amoeba arises from a real-valued partition function when the positivity condition for pre-exponential terms is relaxed, and families of signatures are taken into account. This notion lets us explore special types of constraints when we focus on those signatures that preserve particular properties. Specifically, we look at sums of determinantal type, and main attention is paid to a distinguished class of soliton solutions of the Kadomtsev-Petviashvili (KP) II equation. A characterization of the signatures preserving the determinantal form, as well as the signatures compatible with the KP II equation, is provided: both of them are reduced to choices of signs for columns and rows of a coefficient matrix, and they satisfy the whole KP hierarchy. Interpretations in term of information-theoretic properties, geometric characteristics, and the relation with tropical limits are discussed.Comment: 42 pages, 11 figures. Section 7.1 has been added, the organization of the paper has been change

Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing

ROSAT X-ray sources in the field of the LMC I.Total LMC gas from the background AGN spectral fits

We analyzed a sample of 26 background X-ray sources in a ~60 square degree field of the Large Magellanic Cloud observed with the ROSAT PSPC. The sample has been selected from previously classified and optically identified X-ray sources. In addition pointlike and spectrally hard sources with at least 100 to 200 observed counts have been used for the analysis. We performed X-ray spectral fitting and derived total hydrogen absorbing column densities due to LMC gas in the range 10^20 - 2. 10^21 cm^-2. We compared these columns with the HI columns derived from a 21-cm Parkes survey of the LMC. For 7 optically identified sources we find, within the uncertainties derived from the X-ray spectral fit, agreement for both columns. For further 19 sources we constrain the LMC columns from the X-ray spectral fit assuming that the powerlaw photon index is that of AGN type spectra. We derive for 20 sources gas columns which are within the uncertainties in agreement with the HI columns. We derive for two background sources (RX J0536.9-6913 and RX J0547.0-7040) hydrogen absorbing column densities due to LMC gas, which are in excess to the HI columns. These sources - located in regions of large (~3. 10^21 cm^-2) LMC HI column densities - could be seen through additional gas which may be warm and diffuse, cold or molecular. For 10 sources we derive upper limits for the gas columns additional to HI and constrain the molecular mass fraction to <(30-140)%.Comment: Accepted by A&

Regularly alternating spin-1/2 anisotropic XY chains: The ground-state and thermodynamic properties

Using the Jordan-Wigner transformation and continued fractions we calculate rigorously the thermodynamic quantities for the spin-1/2 transverse Ising chain with periodically varying intersite interactions and/or on-site fields. We consider in detail the properties of the chains having a period of the transverse field modulation equal to 3. The regularly alternating transverse Ising chain exhibits several quantum phase transition points, where the number of transition points for a given period of alternation strongly depends on the specific set of the Hamiltonian parameters. The critical behavior in most cases is the same as for the uniform chain. However, for certain sets of the Hamiltonian parameters the critical behavior may be changed and weak singularities in the ground-state quantities appear. Due to the regular alternation of the Hamiltonian parameters the transverse Ising chain may exhibit plateau-like steps in the zero-temperature dependence of the transverse magnetization vs. transverse field and many-peak temperature profiles of the specific heat. We compare the ground-state properties of regularly alternating transverse Ising and transverse XX chains and of regularly alternating quantum and classical chains. Making use of the corresponding unitary transformations we extend the elaborated approach to the study of thermodynamics of regularly alternating spin-1/2 anisotropic XY chains without field. We use the exact expression for the ground-state energy of such a chain of period 2 to discuss how the exchange interaction anisotropy destroys the spin-Peierls dimerized phase

Hadronic WW production and the Gottfried Sum Rule

The difference in production rate between $W^+$ and $W^-$ at hadron colliders is very sensitive to the the difference between up- and down-quark distributions in the proton. This sensitivity allows for a variety of useful measurements. We consider the difference $d_s(x,Q^2) - u_s(x,Q^2)$ in the sea distributions and the difference $\Delta u(x,Q^2) - \Delta d(x,Q^2)$ in the polarized parton distribution functions. In both cases we construct an asymmetry to reduce systematic uncertainties. Although we discuss measurements at the Tevatron and future hadron colliders, we find that the Brookhaven Relativistic Heavy Ion Collider (RHIC) is the most appropriate hadron collider for these measurements.Comment: 19 pages (20 figures available from the authors), MAD/PH/74

Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases—A Review of Applications and Perspectives

The development of good quality and affordable ultrasound machines has led to the establishment and implementation of numerous point-of-care ultrasound (POCUS) protocols in various medical disciplines. POCUS for major infectious diseases endemic in tropical regions has received less attention, despite its likely even more pronounced benefit for populations with limited access to imaging infrastructure. Focused assessment with sonography for HIV-associated TB (FASH) and echinococcosis (FASE) are the only two POCUS protocols for tropical infectious diseases, which have been formally investigated and which have been implemented in routine patient care today. This review collates the available evidence for FASH and FASE, and discusses sonographic experiences reported for urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS protocols are suggested and technical as well as training aspects in the context of resource-limited settings are reviewed. Using the focused approach for tropical infectious diseases will make ultrasound diagnosis available to patients who would otherwise have very limited or no access to medical imaging