Therapeutic antibodies: current state and future trends--is a paradigm change coming soon?

Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the "magic bullet" has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to$11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1-2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use

Egalitarianism in convex fuzzy games

cooperative games;algorithm

Convex fuzzy games and participation monotonic allocation schemes

90D12;03E72cooperative games

Hypercubes and compromise values for cooperative fuzzy games

90D12;03E72cooperative games

2MASSJ22560844+5954299: the newly discovered cataclysmic star with the deepest eclipse

Context: The SW Sex stars are assumed to represent a distinguished stage in CV evolution, making it especially important to study them. Aims: We discovered a new cataclysmic star and carried out prolonged and precise photometric observations, as well as medium-resolution spectral observations. Modelling these data allowed us to determine the psysical parameters and to establish its peculiarities. Results: The newly discovered vataclysmic variable 2MASSJ22560844+5954299 shows the deepest eclipse amongst the known nova-like stars. It was reproduced by totally covering a very luminous accretion disk by a red secondary component. The temperature distribution of the disk is flatter than that of steady-state disk. The target is unusual with the combination of a low mass ratio q~1.0 (considerably below the limit q=1.2 of stable mass transfer of CVs) and an M-star secondary. The intensity of the observed three emission lines, H_alpha, He 5875, and He 6678, sharply increases around phase 0.0, accompanied by a Doppler jump to the shorter wavelength. The absence of eclipses of the emission lines and their single-peaked profiles means that they originate mainly in a vertically extended hot-spot halo. The emission H_alpha line reveals S-wave wavelength shifts with semi-amplitude of around 210 km/s and phase lag of 0.03. Conclusions: The non-steady-state emission of the luminous accretion disk of 2MASSJ22560844+5954299 was attributed to the low viscosity of the disk matter caused by its unusually high temperature. The star shows all spectral properties of an SW Sex variable apart from the 0.5 central absorption.Comment: Accepted for publication in Astronomy & Astrophysics. 12 pages, 11 figures, 6 table

Nonlinear Terms of MHD Equations for Homogeneous Magnetized Shear Flow

We have derived the full set of MHD equations for incompressible shear flow of a magnetized fluid and considered their solution in the wave-vector space. The linearized equations give the famous amplification of slow magnetosonic waves and describe the magnetorotational instability. The nonlinear terms in our analysis are responsible for the creation of turbulence and self-sustained spectral density of the MHD (Alfven and pseudo-Alfven) waves. Perspectives for numerical simulations of weak turbulence and calculation of the effective viscosity of accretion disks are shortly discussed in k-space.Comment: 13 pages, no figures; AIP Conference Proceedings 1356, Proceedings of the School and Workshop on Space Plasma Physics (1--12 September 2010, Kiten, Bulgaria), American Institute of Physics, Melville, NY, 201

Unusual persistence of superconductivity against high magnetic fields in the strongly-correlated iron-chalcogenide film FeTe:Ox_{x}

We report an unusual persistence of superconductivity against high magnetic fields in the iron chalcogenide film FeTe:O$_{x}$ below ~ 2.5 K. Instead of saturating like a mean-field behavior with a single order parameter, the measured low-temperature upper critical field increases progressively, suggesting a large supply of superconducting states accessible via magnetic field or low-energy thermal fluctuations. We demonstrate that superconducting states of finite momenta can be realized within the conventional theory, despite its questionable applicability. Our findings reveal a fundamental characteristic of superconductivity and electronic structure in the strongly-correlated iron-based superconductors.Comment: 10 pages, 3 figure