Digital media - social memory: remembering in digitally networked times

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Drug development: Lessons from nature.

Natural products have been acknowledged for numerous years as a vital source of active ingredients in therapeutic agents. In particular, the use of active ingredients derived from plants for use in microbial natural products have long been used before the dawn of modern medicine. From ancient times, the efficacy of natural products has been associated with the chemistry, biochemistry and synthetic activities of natural products. Thus, with scientific advancement in modern molecular and cellular biology, analytical chemistry and pharmacology, the unique properties of these natural products are being harnessed in order to exploit the chemical and structural diversity and biodiversity of these types of products in relation to their therapeutic effect. Often, new molecules of interest in drug design units focus on the rearrangement of chemical entities or structural isomers of naturally occurring products in order to generate new molecules; these may be formulated into clinically useful therapies

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

On the importance of testing gravity at distances less than 1cm

If the mechanism responsible for the smallness of the vacuum energy is consistent with local quantum field theory, general arguments suggest the existence of at least one unobserved scalar particle with Compton wavelength bounded from below by one tenth of a millimeter. We show that this bound is saturated if vacuum energy is a substantial component of the energy density of the universe. Therefore, the success of cosmological models with a significant vacuum energy component suggests the existence of new macroscopic forces with range in the sub-millimeter region. There are virtually no experimental constraints on the existence of quanta with this range of interaction.Comment: 9 pages TeX, 2 eps figures, uses mtexsis.tex and epsf.tex. Entry in 1996 Gravity Research Foundation essay competition. To be published in the Journal of General Relativity and Gravitatio

Boundary-layer friction in midlatitude cyclone

Results from an idealized three-dimensional baroclinic life-cycle model are interpreted in a potential vorticity (PV) framework to identify the physical mechanisms by which frictional processes acting in the atmospheric boundary layer modify and reduce the baroclinic development of a midlatitude storm. Considering a life cycle where the only non-conservative process acting is boundary-layer friction, the rate of change of depth-averaged PV within the boundary layer is governed by frictional generation of PV and the flux of PV into the free troposphere. Frictional generation of PV has two contributions: Ekman generation, which is directly analogous to the well-known Ekman-pumping mechanism for barotropic vortices, and baroclinic generation, which depends on the turning of the wind in the boundary layer and low-level horizontal temperature gradients. It is usually assumed, at least implicitly, that an Ekman process of negative PV generation is the mechanism whereby friction reduces the strength and growth rates of baroclinic systems. Although there is evidence for this mechanism, it is shown that baroclinic generation of PV dominates, producing positive PV anomalies downstream of the low centre, close to developing warm and cold fronts. These PV anomalies are advected by the large-scale warm conveyor belt flow upwards and polewards, fluxed into the troposphere near the warm front, and then advected westwards relative to the system. The result is a thin band of positive PV in the lower troposphere above the surface low centre. This PV is shown to be associated with a positive static stability anomaly, which Rossby edge wave theory suggests reduces the strength of the coupling between the upper- and lower-level PV anomalies, thereby reducing the rate of baroclinic development. This mechanism, which is a result of the baroclinic dynamics in the frontal regions, is in marked contrast with simple barotropic spin-down ideas. Finally we note the implications of these frictionally generated PV anomalies for cyclone forecasting

A GIT interpretration of the Harder-Narasimhan filtration

An unstable torsion free sheaf on a smooth projective variety gives a GIT unstable point in certain Quot scheme. To a GIT unstable point, Kempf associates a "maximally destabilizing" 1-parameter subgroup, and this induces a filtration of the torsion free sheaf. We show that this filtration coincides with the Harder-Narasimhan filtration.Comment: 19 pages; Comments of the referees and references added. The construction for holomorphic pairs (Sections 6 and 7 from previous version) will appear in a further publication. To appear in Rev. Mat Complutens