920 research outputs found
Instanton Contribution to the Proton and Neutron Electric Form Factors
We study the instanton contribution to the proton and neutron electric form
factors. Using the single instanton approximation, we perform the calculations
in a mixed time-momentum representation in order to obtain the form factors
directly in momentum space. We find good agreement with the experimentally
measured electric form factor of the proton. For the neutron, our result falls
short of the experimental data. We argue that this discrepancy is due to the
fact that we neglect the contribution of the sea quarks. We compare to lattice
calculations and a relativistic version of the quark-diquark model.Comment: 8 pages, 5 figures, updated references, to appear in Phys. Lett.
What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands
Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand.
We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates.
Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging
Gad65 is recognized by t-cells, but not by antibodies from nod-mice
Since the 64kDa-protein glutamic acid decarboxylase (GAD) is one of the major autoantigens in T-cell mediated Type 1 diabetes, its relevance as a T-cell antigen needs to be clarified. After isolation of splenic T-cells from non-obese diabetic (NOD) mice, a useful model for human Type 1 diabetes, we found that these T-cells proliferate spontaneously when incubated with human GAD65, but only marginally after incubation with GAD67, both recombinated in the baculovirus system. No effect was observed with non-diabetic NOD mice or with T-cells from H-2 identical NON-NOD-H-2g7 control mice. It has been published previously that NOD mice develop autoantibodies against a 64kDa protein detected with mouse beta cells. In immunoprecipitation experiments with sera from the same NOD mice and 33S-methionine-labelled GAD, no autoantibody binding could be detected. We conclude firstly that GAD65 is an important T-cell antigen which is relevant early in the development of Type 1 diabetes and secondly that there is an antigenic epitope in the human GAD65 molecule recognized by NOD T-cells, but not by NOD autoantibodies precipitating conformational epitopes. Our results therefore provide further evidence that GAD65 is a T-cell antigen in NOD mice, being possibly also involved in very early processes leading to the development of human Type 1 diabetes
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On Ex Situ NMR: Developing portable low-cost and/or single sided NMR/MRI
Nuclear magnetic resonance spectroscopy (NMR) is of unsurpassed versatility in its ability to non-destructively probe for chemical identity. Portable, low-cost NMR sensors would enable on site identification of potentially hazardous substances, such as signatures from production of nuclear, chemical, and biological weapon agents, narcotics, explosives, toxins, and poisons. There exist however problems that need to be considered in the case of such sensors: (a) small-scale magnets produce inhomogeneous magnetic fields and therefore undesired Larmor frequency distributions that conceal much of the useful spectral information, and (b) sensitivity in most experiments decreases due to the inherently low and strongly inhomogeneous fields associated with portable instruments. Our approach is to: (a) try to improve the field of low cost magnets either with hardware (e.g. magnet design and construction of ''shim coils'') or via special pulse sequences, where the field is ''effectively shimmed'' to appear homogeneous to the sample, and (b) to use microcoils to improve sensitivity and to allow focusing in smaller regions and therefore smaller static field variations. We have been working in setting up a table top, 2-Tesla permanent Halbach magnet system for tabletop NMR. The Spectrometer console is a Tecmag Apollo, controlled by a dell notebook. Currently an external linear chemagnetics rf amplifier is being used, though the power requirements for our system are quite low (a few Watts). The Magnetic Resonance lab in LLNL, has developed several types and sizes of microcoils, which have been proven to perform well for NMR experiments. We have evaluated an rf, 360 {micro}m O.D., microcoil probe that was built previously. We have finished mapping the magnetic field of the magnet. In the optimal position (in terms of field quality), the field inhomogeneity was at 17ppm. Preliminary fluorine spectra with a resolved two peak separation have now been obtained. For the field, as mapped, we have initial designs of first degree shimming, or gradient coils (linear correction to the field). We have calculated ''shim pulses'' to effectively shim the mapped field, for ideal gradient coils. These calculations will be repeated after the coils will be built and evaluated
Щодо утворення сімейств атомарних радіальних базисних функцій
Наведено схему побудови сімейств атомарних радіальних базисних функцій, які є нескінченно диференційовними фінітними розв'язками функціонально-диференціальних рівнянь, породжених операторами Лапласа та Гельмгольца.The scheme of building a family of atomic radial basis functions which are infinitely differentiable finite solutions of the functional-differential equations containing the Laplace and Helmholtz operators is introduced
Extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors
Nucleon electromagnetic form factor data (including recent data) is fitted
with models that respect the confinement and asymptotic freedom properties of
QCD. Gari-Krumpelmann (GK) type models, which include the major vector meson
pole contributions and at high momentum transfer conform to the predictions of
perturbative QCD, are combined with Hohler-Pietarinen (HP) models, which also
include the width of the rho meson and the addition of higher mass vector meson
exchanges, but do not evolve into the explicit form of PQCD at high momentum
transfer. Different parameterizations of the GK model's hadronic form factors,
the effect of including the width of the rho meson and the addition of the next
(in mass) isospin 1 vector meson are considered. The quality of fit and the
consistency of the parameters select three of the combined HP/GK type models.
Projections are made to the higher momentum transfers which are relevant to
electron-deuteron experiments. The projections vary little for the preferred
models, removing much of the ambiguity in electron-nucleus scattering
predictions.Comment: 18pp, 7 figures, using RevTeX with BoxedEPS macros; 1 new figure,
minor textual changes; email correspondence to [email protected]
Effect of recent R_p and R_n measurements on extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors
The Gari-Krumpelmann (GK) models of nucleon electromagnetic form factors, in
which the rho, omega, and phi vector meson pole contributions evolve at high
momentum transfer to conform to the predictions of perturbative QCD (pQCD), was
recently extended to include the width of the rho meson by substituting the
result of dispersion relations for the pole and the addition of rho' (1450)
isovector vector meson pole. This extended model was shown to produce a good
overall fit to all the available nucleon electromagnetic form factor (emff)
data. Since then new polarization data shows that the electric to magnetic
ratios R_p and R_n obtained are not consistent with the older G_{Ep} and G_{En}
data in their range of momentum transfer. The model is further extended to
include the omega' (1419) isoscalar vector meson pole. It is found that while
this GKex cannot simultaneously fit the new R_p and the old G_{En} data, it can
fit the new R_p and R_n well simultaneously. An excellent fit to all the
remaining data is obtained when the inconsistent G_{Ep} and G_{En} is omitted.
The model predictions are shown up to momentum transfer squared, Q^2, of 8
GeV^2/c^2.Comment: 14 pages, 8 figures, using RevTeX4; email correspondence to
[email protected] ; minor typos corrected, figures added, conclusions
extende
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Magnetic Resonance Based Diagnostics for Polymer Production and Surveillance
In an effort to develop a magnetic resonance based diagnostic tool to be used for polymer production and surveillance, we have investigated the use of magnetic resonance imaging (MRI) and unilateral relaxometry. MRI provides a spatial map of the polymer, which can be correlated to the structure heterogeneity. Though highly detailed information can be obtained with MRI, the high equipment cost and expertise required to operate the system makes it a poor choice for a production setting. Unilateral relaxometry via the NMR MOUSE provides rapid, inexpensive polymer screening, useful in the development in new polymer parts or to identify potentially defective components. The NMR ProFiler (originally called the NMR MOUSE) was procured by Kansas City originally for production support of the W80 LEP with future applications as a surveillance diagnostic. A robotic autosampler has been designed allowing the detection of several components without the need for any human interaction. A summary of the qualification experiments and results to date from the ProFiler and the robotic unit will be presented
Neutron charge form factor at large
The neutron charge form factor is determined from an analysis of
the deuteron quadrupole form factor data. Recent calculations, based
on a variety of different model interactions and currents, indicate that the
contributions associated with the uncertain two-body operators of shorter range
are relatively small for , even at large momentum transfer . Hence,
can be extracted from at large without undue
systematic uncertainties from theory.Comment: 8 pages, 3 figure
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