N-terminal modification of VEGF-A C terminus-derived peptides delineates structural features involved in neuropilin-1 binding and functional activity

The interaction between VEGF-A and its neuropilin (NRP) receptors mediates a number of important biological effects. NRP1 and the related molecule NRP2 are widely expressed on multiple tumour types and throughout the tumour vasculature, and are emerging as critical molecules required for the progression of angiogenic diseases. Given the increasing evidence supporting a role for NRP1 in tumour development, there is growing interest in developing inhibitors of NRP1 interactions with VEGF and its other ligands. In order to probe the interaction we synthesised a number of exon 7- and 8-derived bicyclic peptides with N-terminal lipophilic groups and found a simple N-octanoyl derivative (EG00086) to be the most potent and functionally active. Detailed modelling studies indicated that new intramolecular hydrogen bonds were formed, stabilising the structure and possibly contributing to the potency. Removal of a salt bridge between D142 and R164 implicated in VEGF-A binding to neuropilin-1 had a minor effect on potency. Isothermal calorimetry was used to assess binding of EG00086 to NRP1 and NRP2, and the stability of the peptide in serum and in vivo was investigated. EG00086 is a potent blocker of VEGF-promoted cellular adhesion to extracellular matrices, and phosphorylation of p130Cas contributes to this effect

Jet Tomography in the Forward Direction at RHIC

Hadron production at high-$p_T$ displays a strong suppression pattern in a wide rapidity region in heavy ion collisions at RHIC energies. This finding indicates the presence of strong final state effects for both transversally and longitudinally traveling partons, namely induced energy loss. We have developed a perturbative QCD based model to describe hadron production in $pp$ collision, which can be combined with the Glauber -- Gribov model to describe hadron production in heavy ion collisions. Investigating $AuAu$ and $CuCu$ collisions at energy $\sqrt{s}=200$ $A$GeV at mid-rapidity, we find the opacity of the strongly interacting hot matter to be proportional to the participant nucleon number. Considering forward rapidities, the suppression pattern indicates the formation of a longitudinally contracted dense deconfined zone in central heavy ion collisions. We determine parameters for the initial geometry from the existing data.Comment: 6 pages for Hot Quarks '06 Conferenc

Quantum metrological triangle experiment at LNE: measurements on a three-junction R-pump using a 20 000:1 winding ratio cryogenic current comparator

International audienceThe direct closure of the quantum metrological triangle consists in achieving Ohm's law with the three effects used and investigated in quantum electrical metrology: the Josephson effect (JE), the quantum Hall effect (QHE) and the single-electron tunnelling effect (SET). The aim is to check the consistency of the phenomenological constants KJ, RK and QX associated with these effects and theoretically expressed with the fundamental constants e and h (elementary charge and Planck constant, respectively). Such an experiment is a contribution to a future redefinition of the International System of units (SI). In this paper, the experimental setup developed at LNE is described and the main obtained results are given. From a set of four measurements, agreement at a level of 1.3 parts in 105 was found between the quantum charge involved in the SET, i.e. QX, and the CODATA value of the elementary charge. The best measurement has shown a relative type-A uncertainty of 1.9 parts in 106, while the amplitude of the current generated by a metallic electron pump was as low as 3.6 pA

PATENTED PATTERNS: On the art and science of patterns. A critical inquiry.

This is a conference paper.The present paper proposes a critical reflection on the existing relationship between patterns, algorithms and their patentable status. Based on a series of legal actions related to the use of patterns (Robert Lang against Sarah Morris, Mexican indigenous peoples against Isabel Marant, Apple patent on some gestures, etc.) it will analyse the already existing legal interpretations of what a pattern is and will discuss in which way these cases can establish a precedent for today’s digitalized environments. Defined both as form of stylistic and cultural expression, as well as logical forms, patterns are becoming elements of high importance for the present digital modelization technologies (see, for example, pattern recognition algorithms). Therefore, the legal status of a pattern is becoming a field of political battle. Notions like author and collective author, cultural tradition and logical form, creative commons and intellectual property are at stake in this context. The implications are of social, political and economic importance and this paper will sketch out some of the short-comings when it comes to their use and application, their implicit ideologies, as well as arts and sciences disciplinary divisions