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

Feynman rules for the rational part of the Electroweak 1-loop amplitudes

We present the complete set of Feynman rules producing the rational terms of kind R_2 needed to perform any 1-loop calculation in the Electroweak Standard Model. Our results are given both in the 't Hooft-Veltman and in the Four Dimensional Helicity regularization schemes. We also verified, by using both the 't Hooft-Feynman gauge and the Background Field Method, a huge set of Ward identities -up to 4-points- for the complete rational part of the Electroweak amplitudes. This provides a stringent check of our results and, as a by-product, an explicit test of the gauge invariance of the Four Dimensional Helicity regularization scheme in the complete Standard Model at 1-loop. The formulae presented in this paper provide the last missing piece for completely automatizing, in the framework of the OPP method, the 1-loop calculations in the SU(3) X SU(2) X U(1) Standard Model.Comment: Many thanks to Huasheng Shao for having recomputed, independently of us, all of the ${\rm R_2}$ effective vertices. Thanks to his help and by comparing with an independent computation we performed in a general $R_\xi$ gauge, we could fix, in the present version, the following formulae: the vertex $A l \bar l$ in Eq. (3.6), the vertex $Z \phi^+ \phi^-$ in Eq. (3.8), Eqs (3.16), (3.17) and (3.18

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

Competing for Refugees: A Market-Based Solution to a Humanitarian Crisis

The current refugee crisis demands novel legal solutions, and new ways of summoning the political will to implement them. As a matter of national incentives, the goal must be to design mechanisms that discourage countries of origin from creating refugees, and encourage host countries to welcome them. One way to achieve this would be to recognize that persecuted refugee groups have a financial claim against their countries of origin, and that this claim can be traded to host nations in exchange for acceptance. Modifications to the international apparatus would be necessary, but the basic legal elements of this proposal already exist. In short, international law can and should give refugees a legal asset, give host nations incentives to accept them, and give oppressive countries of origin the bill

Tensorial Reconstruction at the Integrand Level

We present a new approach to the reduction of one-loop amplitudes obtained by reconstructing the tensorial expression of the scattering amplitudes. The reconstruction is performed at the integrand level by means of a sampling in the integration momentum. There are several interesting applications of this novel method within existing techniques for the reduction of one-loop multi-leg amplitudes: to deal with numerically unstable points, such as in the vicinity of a vanishing Gram determinant; to allow for a sampling of the numerator function based on real values of the integration momentum; to optimize the numerical reduction in the case of long expressions for the numerator functions.Comment: 20 pages, 2 figure

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

Potentiality in Biology

We take the potentialities that are studied in the biological sciences (e.g., totipotency) to be an important subtype of biological dispositions. The goal of this paper is twofold: first, we want to provide a detailed understanding of what biological dispositions are. We claim that two features are essential for dispositions in biology: the importance of the manifestation process and the diversity of conditions that need to be satisfied for the disposition to be manifest. Second, we demonstrate that the concept of a disposition (or potentiality) is a very useful tool for the analysis of the explanatory practice in the biological sciences. On the one hand it allows an in-depth analysis of the nature and diversity of the conditions under which biological systems display specific behaviors. On the other hand the concept of a disposition may serve a unificatory role in the philosophy of the natural sciences since it captures not only the explanatory practice of biology, but of all natural sciences. Towards the end we will briefly come back to the notion of a potentiality in biology

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

Is the Shroud of Turin in Relation to the Old Jerusalem Historical Earthquake?

Phillips and Hedges suggested, in the scientific magazine Nature (1989), that neutron radiation could be liable of a wrong radiocarbon dating, while proton radiation could be responsible of the Shroud body image formation. On the other hand, no plausible physical reason has been proposed so far to explain the radiation source origin, and its effects on the linen fibres. However, some recent studies, carried out by the first author and his Team at the Laboratory of Fracture Mechanics of the Politecnico di Torino, found that it is possible to generate neutron emissions from very brittle rock specimens in compression through piezonuclear fission reactions. Analogously, neutron flux increments, in correspondence to seismic activity, should be a result of the same reactions. A group of Russian scientists measured a neutron flux exceeding the background level by three orders of magnitude in correspondence to rather appreciable earthquakes (4th degree in Richter Scale). The authors consider the possibility that neutron emissions by earthquakes could have induced the image formation on Shroud linen fibres, trough thermal neutron capture by Nitrogen nuclei, and provided a wrong radiocarbon dating due to an increment in C(14,6)content. Let us consider that, although the calculated integral flux of 10^13 neutrons per square centimetre is 10 times greater than the cancer therapy dose, nevertheless it is100 times smaller than the lethal dose.Comment: 13 pages, 1 figur

Scattering AMplitudes from Unitarity-based Reduction Algorithm at the Integrand-level

SAMURAI is a tool for the automated numerical evaluation of one-loop corrections to any scattering amplitudes within the dimensional-regularization scheme. It is based on the decomposition of the integrand according to the OPP-approach, extended to accommodate an implementation of the generalized d-dimensional unitarity-cuts technique, and uses a polynomial interpolation exploiting the Discrete Fourier Transform. SAMURAI can process integrands written either as numerator of Feynman diagrams or as product of tree-level amplitudes. We discuss some applications, among which the 6- and 8-photon scattering in QED, and the 6-quark scattering in QCD. SAMURAI has been implemented as a Fortran90 library, publicly available, and it could be a useful module for the systematic evaluation of the virtual corrections oriented towards automating next-to-leading order calculations relevant for the LHC phenomenology.Comment: 35 pages, 7 figure