Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

A visual guide for lower limb prothetic alignment

A novel method to provide an objective visual guide during lower limb prosthetic alignment is proposed. A customized ambulatory device was built to collect kinematic and temporal gait data from 3 subjects walking in four different experiment setups. Multiple gait events within a gait cycle and stride time were derived as feature variables and were pre-processed using Principle Component Analysis (PCA). Distinctive clusters due to different walking setups were noticed in a PCA plot in two dimensions. Dispersion of each clusters and distances amongst each other explains the walking variability and differences under different setups

A model for orientation effects in electron‐transfer reactions

A method for solving the single‐particle Schrödinger equation with an oblate spheroidal potential of finite depth is presented. The wave functions are then used to calculate the matrix element T_BA which appears in theories of nonadiabatic electron transfer. The results illustrate the effects of mutual orientation and separation of the two centers on TBA. Trends in these results are discussed in terms of geometrical and nodal structure effects. Analytical expressions related to T_BA for states of spherical wells are presented and used to analyze the nodal structure effects for T_BA for the spheroidal wells

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Next-to-leading order QCD predictions for W+W+jj production at the LHC

Because the LHC is a proton-proton collider, sizable production of two positively charged W-bosons in association with two jets is possible. This process leads to a distinct signature of same sign high-pt leptons, missing energy and jets. We compute the NLO QCD corrections to the QCD-mediated part of pp -> W+W+jj. These corrections reduce the dependence of the production cross-section on the renormalization and factorization scale to about +- 10 percent. We find that a large number of W+W+jj events contain a relatively hard third jet. The presence of this jet should help to either pick up the W+W+jj signal or to reject it as an unwanted background.Comment: 15 pages, 5 (lovely) figures, v3 accepted for publication in JHEP, corrects tables in appendi

Instantaneous Shape Sampling - a model for the γ\gamma-absorption cross section of transitional nuclei

The influence of the quadrupole shape fluctuations on the dipole vibrations in transitional nuclei is investigated in the framework of the Instantaneous Shape Sampling Model, which combines the Interacting Boson Model for the slow collective quadrupole motion with the Random Phase Approximation for the rapid dipole vibrations. Coupling to the complex background configurations is taken into account by folding the results with a Lorentzian with an energy dependent width. The low-energy energy portion of the $\gamma$- absorption cross section, which is important for photo-nuclear processes, is studied for the isotopic series of Kr, Xe, Ba, and Sm. The experimental cross sections are well reproduced. The low-energy cross section is determined by the Landau fragmentation of the dipole strength and its redistribution caused by the shape fluctuations. Collisional damping only wipes out fluctuations of the absorption cross section, generating the smooth energy dependence observed in experiment. In the case of semi-magic nuclei, shallow pygmy resonances are found in agreement with experiment