Review of the biotechnology research and development (R and D) in OECD countries concerning biological drugs

The pharmaceutical industry is among high technology industries that needs considerable attention in research and development. Overall, the processes that a drug must go through from its production in the laboratory, to clinical trials on certain groups, to the drug being licensed and finally planning for its marketing makes it different to any other product. Boosting research and development capability in this industry as well as saving patients’ lives is also essential in controlling the costs of importing drugs. According to this point of view, having suitable R and D strategies in the pharmaceutical sector becomes very important for every country. In this study, we aimed to review several studies concerning biological drugs R and D in selected countries. Since the discussions in relation to the R and D within the pharmaceutical sector about biological drugs come under the umbrella of innovation system of each country. By reviewing the pharmaceutical innovation system studies of selected OECD countries including Norway, Germany and Japan, we aimed to look at the main factors in national R and D system, the trading system conditions, R and D co-operations, human resources, financial matters, entrepreneurship, the market, R and D policy making and coordination of different organizations and main support policies within the biological drugs system.Key words: R and D, biotechnology, biological drugs

Big Bang Nucleosynthesis Constraints on Primordial Magnetic Fields

We reanalyze the effect of magnetic fields in BBN, incorporating several features which were omitted in previous analyses. We find that the effects of coherent magnetic fields on the weak interaction rates and the electron thermodynamic functions (\rhoe, \Pe, and \drhoedt ) are unimportant in comparison to the contribution of the magnetic field energy density in BBN. In consequence the effect of including magnetic fields in BBN is well approximated numerically by treating the additional energy density as effective neutrino number. A conservative upper bound on the primordial magnetic field, parameterized as $\zeta=2eB_{rms}/(T_\nu^2)$, is $\zeta \le 2$ ($\rho_B < 0.27 \rho_\nu$). This bound can be stronger than the conventional bound coming from the Faraday rotation measures of distant quasars if the cosmological magnetic field is generated by a causal mechanism.Comment: Latex, 20 pages, 3 uuencoded figures appende

Testing The Friedmann Equation: The Expansion of the Universe During Big-Bang Nucleosynthesis

In conventional general relativity, the expansion rate H of a Robertson-Walker universe is related to the energy density by the Friedmann equation. Aside from the present day, the only epoch at which we can constrain the expansion history in a model-independent way is during Big-Bang Nucleosynthesis (BBN). We consider a simple two-parameter characterization of the behavior of H during BBN and derive constraints on this parameter space, finding that the allowed region of parameter space is essentially one-dimensional. We also study the effects of a large neutrino asymmetry within this framework. Our results provide a simple way to compare an alternative cosmology to the observational requirement of matching the primordial abundances of the light elements.Comment: 18 pages, Final version to be published in Phys. Rev.

Solar Neutrino Constraints on the BBN Production of Li

Using the recent WMAP determination of the baryon-to-photon ratio, 10^{10} \eta = 6.14 to within a few percent, big bang nucleosynthesis (BBN) calculations can make relatively accurate predictions of the abundances of the light element isotopes which can be tested against observational abundance determinations. At this value of \eta, the Li7 abundance is predicted to be significantly higher than that observed in low metallicity halo dwarf stars. Among the possible resolutions to this discrepancy are 1) Li7 depletion in the atmosphere of stars; 2) systematic errors originating from the choice of stellar parameters - most notably the surface temperature; and 3) systematic errors in the nuclear cross sections used in the nucleosynthesis calculations. Here, we explore the last possibility, and focus on possible systematic errors in the He3(\alpha,\gamma)Be7 reaction, which is the only important Li7 production channel in BBN. The absolute value of the cross section for this key reaction is known relatively poorly both experimentally and theoretically. The agreement between the standard solar model and solar neutrino data thus provides additional constraints on variations in the cross section (S_{34}). Using the standard solar model of Bahcall, and recent solar neutrino data, we can exclude systematic S_{34} variations of the magnitude needed to resolve the BBN Li7 problem at > 95% CL. Additional laboratory data on He3(\alpha,\gamma)Be7 will sharpen our understanding of both BBN and solar neutrinos, particularly if care is taken in determining the absolute cross section and its uncertainties. Nevertheless, it already seems that this ``nuclear fix'' to the Li7 BBN problem is unlikely; other possible solutions are briefly discussed.Comment: 21 pages, 3 ps figure

Regular and chaotic vibration in a piezoelectric energy harvester

We examine regular and chaotic responses of a vibrational energy harvester composed of a vertical beam and a tip mass. The beam is excited horizontally by a harmonic inertial force while mechanical vibrational energy is converted to electrical power through a piezoelectric patch. The mechanical resonator can be described by single or double well potentials depending on the gravity force from the tip mass. By changing the tip mass we examine bifurcations from single well oscillations, to regular and chaotic vibrations between the potential wells. The appearance of chaotic responses in the energy harvesting system is illustrated by the bifurcation diagram, the corresponding Fourier spectra, the phase portraits, and is confirmed by the 0–1 test. The appearance of chaotic vibrations reduces the level of harvested energy

Constraining Strong Baryon-Dark Matter Interactions with Primordial Nucleosynthesis and Cosmic Rays

Self-interacting dark matter (SIDM) was introduced by Spergel & Steinhardt to address possible discrepancies between collisionless dark matter simulations and observations on scales of less than 1 Mpc. We examine the case in which dark matter particles not only have strong self-interactions but also have strong interactions with baryons. The presence of such interactions will have direct implications for nuclear and particle astrophysics. Among these are a change in the predicted abundances from big bang nucleosynthesis (BBN) and the flux of gamma-rays produced by the decay of neutral pions which originate in collisions between dark matter and Galactic cosmic rays (CR). From these effects we constrain the strength of the baryon--dark matter interactions through the ratio of baryon - dark matter interaction cross section to dark matter mass, $s$. We find that BBN places a weak upper limit to this ratio $< 10^8 cm^2/g$. CR-SIDM interactions, however, limit the possible DM-baryon cross section to $< 5 \times 10^{-3} cm^2/g$; this rules out an energy-independent interaction, but not one which falls with center-of-mass velocity as $s \propto 1/v$ or steeper.Comment: 17 pages, 2 figures; plain LaTeX. To appear in PR

Quantifying uncertainties in primordial nucleosynthesis without Monte Carlo simulations

We present a simple method for determining the (correlated) uncertainties of the light element abundances expected from big bang nucleosynthesis, which avoids the need for lengthy Monte Carlo simulations. Our approach helps to clarify the role of the different nuclear reactions contributing to a particular elemental abundance and makes it easy to implement energy-independent changes in the measured reaction rates. As an application, we demonstrate how this method simplifies the statistical estimation of the nucleon-to-photon ratio through comparison of the standard BBN predictions with the observationally inferred abundances.Comment: 22 pages (RevTeX) incl. 8 figures (epsf); Changes: Figs. 5 & 6 combined + typo in Footnote 1 corrected + several stylistic changes; to appear in Phys. Rev.

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL