Radion Potential and Brane Dynamics

We examine the cosmology of the Randall-Sundrum model in a dynamic setting where scalar fields are present in the bulk as well as the branes. This generates a mechanism similar to that of Goldberger-Wise for radion stabilization and the recovery of late-cosmology features in the branes. Due to the induced radion dynamics, the inflating branes roll towards the minimum of the radion potential, thereby exiting inflation and reheating the Universe. In the slow roll part of the potential, the 'TeV' branes have maximum inflation rate and energy as their coupling to the radion and bulk modes have minimum suppresion. Hence, when rolling down the steep end of the potential towards the stable point, the radion field (which appears as the inflaton of the effective 4D theory in the branes) decays very fast, reheats the Universe .This process results decayin a decrease of brane's canonical vacuum energy $\Lambda_4$. However, at the minimum of the potential $\Lambda_4$ is small but not neccessarily zero and the fine-tuning issue remains .Density perturbation constraints introduce an upper bound when the radion stabilizies. Due to the large radion mass and strong suppression to the bulk modes, moduli problems and bulk reheating do not occur. The reheat temperature and a sufficient number of e-folding constraints for the brane-universe are also satisfied. The model therefore recovers the radiation dominated FRW universe.Comment: 16 pages, 3 figures,extraneous sentences removed, 2 footnotes added, some typos correcte

Radiological Features of Giant Cell Tumours of Bone

Introduction The aim of this study was to evaluate radiological measurements to establish the origin of giant cell tumours of bone. Methods A multi-centre retrospective review was conducted of patients with histologically confirmed giant cell tumours of bone. Images were analysed to estimate the centre of the tumour. Measured from the joint line, the ratio between the distance of the centre of the tumour and the physeal scar was calculated. Results Ninety-five patients were included in the study. Two observers found the tumour to be arising from the metaphyseal area in 94% - 97% of the cases. There was good agreement between the measurements of observers (interclass correlation coefficient 0.71). Conclusion Giant cell tumours of bone appear to be arising from the metaphyseal region

Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products

Elucidating the impact of excipient variability on oral product performance in a biopharmaceutical perspective would be beneficial and allow excipient implementation on Quality by Design (QbD) approaches. The current study investigated the impact of varying viscosity of binders (hypromellose (HPMC)) and superdisintegrants (sodium starch glycolate (SSG)) and particle size distribution of lubricants (magnesium stearate (MgSt)) on the in vitro dissolution of a highly and a poorly soluble drug from immediate release formulations. Compendial (pharmacopoeia buffers) and biorelevant (media simulating the gastrointestinal fluids) media and the USP 2 and USP 4 apparatuses were used to assess the exerted excipient effects on drug dissolution. Real-time dissolution UV imaging provided mechanistic insights into disintegration and dissolution of the immediate release formulations. Varying the viscosity type of HPMC or SSG did not significantly affect drug dissolution irrespective of the compound used. Faster drug dissolution was observed when decreasing the particle size of MgSt for the highly soluble drug. The use of real-time dissolution UV Imaging revealed the influential role of excipient variability on tablet disintegration, as for the highly soluble drug, tablets containing high viscosity HPMC or low particle size MgSt disintegrated faster as compared to the control tablets while for the poorly soluble drug, slower tablet disintegration was observed when increasing the viscosity of the HPMC as compared to the control tablets. Changes in drug dissolution when varying excipients may be anticipated if the excipient change has previously affected drug solubility. The use of multivariate data analysis revealed the influential biopharmaceutical factors such as critical excipient types/properties, drug aqueous solubility, medium/hydrodynamic characteristics affecting the impact of excipient variability on in vitro drug dissolution.</p

Surface dissolution UV imaging for characterization of superdisintegrants and their impact on drug dissolution

Superdisintegrants are a key excipient used in immediate release formulations to promote fast tablet disintegration, therefore understanding the impact of superdisintegrant variability on product performance is important. The current study examined the impact of superdisintegrant critical material attributes (viscosity for sodium starch glycolate (SSG), particle size distribution (PSD) for croscarmellose sodium (CCS)) on their performance (swelling) and on drug dissolution using surface dissolution UV imaging. Acidic and basic pharmacopoeia (compendial) media were used to assess the role of varying pH on superdisintegrant performance and its effect on drug dissolution. A highly soluble (paracetamol) and a poorly soluble (carbamazepine) drug were used as model compounds and drug compacts and drug-excipient compacts were prepared for the dissolution experiments. The presence of a swelled SSG or CCS layer on the compact surface, due to the fast excipient hydration capacity, upon contact with dissolution medium was visualized. The swelling behaviour of superdisintegrants depended on excipient critical material attributes and the pH of the medium. Drug dissolution was faster in presence compared to superdisintegrant absence due to improved compact wetting or compact disintegration. The improvement in drug dissolution was less pronounced with increasing SSG viscosity or CCS particle size. Drug dissolution was slightly more complete in basic compared to acidic conditions in presence of the studied superdisintegrants for the highly soluble drug attributed to the increased excipient hydration capacity and the fast drug release through the swelled excipient structure. The opposite was observed for the poorly soluble drug as potentially the improvement in drug dissolution was compromised by drug release from the highly swelled structure. The use of multivariate data analysis revealed the influential role of excipient and drug properties on the impact of excipient variability on drug dissolution.</p

Spectral Line Imaging Observations of 1E0102.2-7219

E0102-72 is the second brightest X-ray source in the Small Magellanic Cloud and the brightest supernova remnant in the SMC. We observed this SNR for ~140 ksec with the High Energy Transmission Gratings (HETG) aboard the Chandra X-ray Observatory. The small angular size and high surface brightness make this an excellent target for HETG and we resolve the remnant into individual lines. We observe fluxes from several lines which include O VIII Ly$\alpha$, Ly$\beta$, and O VII along with several lines from Ne X, Ne IX and Mg XII. These line ratios provide powerful constraints on the electron temperature and the ionization age of the remnant.Comment: To appear in "Young Supernova Remnants" (11th Annual Astrophysics Conference in Maryland), S. S. Holt & U. Hwang (eds), AIP, New York (2001

Multiple motor memories are learned to control different points on a tool.

Skillful object manipulation requires learning the dynamics of objects, linking applied force to motion 1 ,2 . This involves the formation of a motor memory 3 ,4 , which has been assumed to be associated with the object, independent of the point on the object that one chooses to control. Importantly, in manipulation tasks, different control points on an object, such as the rim of a cup when drinking or its base when setting it down, can be associated with distinct dynamics. Here we show that opposing dynamic perturbations, which interfere when controlling a single location on an object, can be learned when each is associated with a separate control point. This demonstrates that motor memory formation is linked to control points on the object, rather than the object per se . We also show that the motor system only generates separate memories for different control points if they are linked to different dynamics, allowing efficient use of motor memory. To account for these results, we develop a normative switching state-space model of motor learning, in which the association between cues (control points) and contexts (dynamics) is learned rather than fixed. Our findings uncover an important mechanism through which the motor system generates flexible and dexterous behavior