Prodrugs: Do They Have Advantages in Clinical Practice?

This is the published version, also available from the publisher at http://adisonline.com/drugs/Abstract/1985/29050/Prodrugs__Do_They_Have_Advantages_in_Clinical.2.aspxProdrugs are pharmacologically inactive chemical derivatives of a drug molecule that require a transformation within the body in order to release the active drug. They are designed to overcome pharmaceutical and/or pharmacokinetically based problems associated with the parent drug molecule that would otherwise limit the clinical usefulness of the drug. The scientific rationale, based on clinical pharmaceutical and chemical experience, for the design of various currently used prodrugs is presented in this review. The examples presented are by no means comprehensive, but are representative of the different ways in which the prodrug approach has been used to enhance the clinical efficacy of various drug molecules

UMass Amherst Framework Principles for Provider Agreements

Rationale and 14 principles to guide investments and agreements with providers for services, infrastructure and content. Produced by the Framework for Provider Agreements Task Force

Active casein coatings and films for perishable foods: Structural properties and shelf-life extension

There is an urgent need to increase the food supplies to fulfil the demands of future generations as the population of the world is expected to grow beyond 10 billion by 2050. An essential component for ensuring global food security is to reduce food losses during the post-harvest stage. Active edible coatings and films are a promising sustainable preservation technology for shelf-life extension of food products by hindering decay kinetics of minimally processed fruits and vegetables (F&V), by restricting the mass transfer of moisture, aroma, or gases and carrying an active compound, such as an antioxidant or antimicrobial. Active protein-based coatings and films have the potential to extend the shelf-life of food products by decreasing their respiration rates, as they exhibit an excellent gas barrier and good mechanical properties as compared to other biopolymeric packaging. Among protein-based biopolymers, casein and its derivatives as packaging films have been extensively studied due to their low cost, complete biodegradability, and availability. Currently, there is no review study focusing on caseinate-based active coating and film, thus, this review aims to give insights on the composition, rheology, structure, and properties of caseinate-based formulations by critically discussing the results presented in the literature. A methodological approach was followed to obtain relevant literature to discuss the influence of additives on the shelf-life of F&V. Furthermore, changes in secondary structure of casein were observed after incorporation of bioactive compounds (i.e., phenolic acids). Likewise, there is a need to explore chemical interactions among bioactive compounds and biopolymer material by using in silico and laboratory trials as food additives have shown to influence the physicochemical properties of film and shelf-life of food products

Status of the Cylindical-GEM project for the KLOE-2 Inner Tracker

The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as Inner Tracker for KLOE-2, the upgrade of the KLOE experiment at the DAFNE phi-factory, will be presented. The R&D includes several activities: i) the construction and complete characterization of the full-size CGEM prototype, equipped with 650 microns pitch 1-D longitudinal strips; ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.Comment: 4 pages, 10 figures, Presented at Vienna Conference on Instrumentation (Feb 15-20, 2010, Vienna, Austria). Submitted to the Proceeding

Passive galaxies as tracers of cluster environments at z~2

Even 10 billion years ago, the cores of the first galaxy clusters are often found to host a characteristic population of massive galaxies with already suppressed star formation. Here we search for distant cluster candidates at z~2 using massive passive galaxies as tracers. With a sample of ~40 spectroscopically confirmed passive galaxies at 1.3<z<2.1, we tune photometric redshifts of several thousands passive sources in the full 2 sq.deg. COSMOS field. This allows us to map their density in redshift slices, probing the large scale structure in the COSMOS field as traced by passive sources. We report here on the three strongest passive galaxy overdensities that we identify in the redshift range 1.5<z<2.5. While the actual nature of these concentrations is still to be confirmed, we discuss their identification procedure, and the arguments supporting them as candidate galaxy clusters (likely mid-10^13 M_sun range). Although this search approach is likely biased towards more evolved structures, it has the potential to select still rare, cluster-like environments close to their epoch of first appearance, enabling new investigations of the evolution of galaxies in the context of structure growth.Comment: 5 pages, 5 figures; A&A Letters, in pres

van der Waals density functionals built upon the electron-gas tradition: Facing the challenge of competing interactions

The theoretical description of sparse matter attracts much interest, in particular for those ground-state properties that can be described by density functional theory (DFT). One proposed approach, the van der Waals density functional (vdW-DF) method, rests on strong physical foundations and offers simple yet accurate and robust functionals. A very recent functional within this method called vdW-DF-cx [K. Berland and P. Hyldgaard, Phys. Rev. B 89, 035412] stands out in its attempt to use an exchange energy derived from the same plasmon-based theory from which the nonlocal correlation energy was derived. Encouraged by its good performance for solids, layered materials, and aromatic molecules, we apply it to several systems that are characterized by competing interactions. These include the ferroelectric response in PbTiO$_3$, the adsorption of small molecules within metal-organic frameworks (MOFs), the graphite/diamond phase transition, and the adsorption of an aromatic-molecule on the Ag(111) surface. Our results indicate that vdW-DF-cx is overall well suited to tackle these challenging systems. In addition to being a competitive density functional for sparse matter, the vdW-DF-cx construction presents a more robust general purpose functional that could be applied to a range of materials problems with a variety of competing interactions

The FMOS-COSMOS survey of star-forming galaxies at z~1.6. IV: Excitation state and chemical enrichment of the interstellar medium

We investigate the physical conditions of ionized gas in high-z star-forming galaxies using diagnostic diagrams based on the rest-frame optical emission lines. The sample consists of 701 galaxies with an Ha detection at $1.4\lesssim z\lesssim1.7$, from the FMOS-COSMOS survey, that represent the normal star-forming population over the stellar mass range $10^{9.6} \lesssim M_\ast/M_\odot \lesssim 10^{11.6}$ with those at $M_\ast>10^{11}~M_\odot$ being well sampled. We confirm an offset of the average location of star-forming galaxies in the BPT diagram ([OIII]/Hb vs. [NII]/Ha), primarily towards higher [OIII]/Hb, compared with local galaxies. Based on the [SII] ratio, we measure an electron density ($n_e=220^{+170}_{-130}~\mathrm{cm^{-3}}$), that is higher than that of local galaxies. Based on comparisons to theoretical models, we argue that changes in emission-line ratios, including the offset in the BPT diagram, are caused by a higher ionization parameter both at fixed stellar mass and at fixed metallicity with additional contributions from a higher gas density and possibly a hardening of the ionizing radiation field. Ionization due to AGNs is ruled out as assessed with Chandra. As a consequence, we revisit the mass-metallicity relation using [NII]/Ha and a new calibration including [NII]/[SII] as recently introduced by Dopita et al. Consistent with our previous results, the most massive galaxies ($M_\ast\gtrsim10^{11}~M_\odot$) are fully enriched, while those at lower masses have metallicities lower than local galaxies. Finally, we demonstrate that the stellar masses, metallicities and star formation rates of the FMOS sample are well fit with a physically-motivated model for the chemical evolution of star-forming galaxies.Comment: 38 pages; Accepted for publication in Ap

THE RED SEQUENCE AT BIRTH IN THE GALAXY CLUSTER Cl J1449+0856 AT z=2

We use. Hubble Space Telescope/WFC3 imaging to study the red population in the IR-selected, X-ray detected, low-mass cluster Cl J1449+0856 at z = 2, one of the few bona fide established clusters discovered at this redshift, and likely a typical progenitor of an average massive cluster today. This study explores the presence and significance of an early red sequence in the core of this structure, investigating the nature of red-sequence galaxies, highlighting environmental effects on cluster galaxy populations at high redshift, and at the same time underlining similarities and differences with other distant dense environments. Our results suggest that the red population in the core of Cl J1449+0856 is made of a mixture of quiescent and dusty star-forming galaxies, with a seedling of the future red sequence already growing in the very central cluster region, and already characterizing the inner cluster core with respect to lower-density environments. On the other hand, the color-magnitude diagram of this cluster is definitely different from that of lower-redshift z less than or similar to 1 clusters, as well as of some rare particularly evolved massive clusters at similar redshift, and it is suggestive of a transition phase between active star formation and passive evolution occurring in the protocluster and established lower-redshift cluster regimes.Peer reviewe

Two-neutron transfer reaction mechanisms in 12^{12}C(6^6He,4^{4}He)14^{14}C using a realistic three-body 6^{6}He model

The reaction mechanisms of the two-neutron transfer reaction $^{12}$C($^6$He,$^4$He) have been studied at 30 MeV at the TRIUMF ISAC-II facility using the SHARC charged-particle detector array. Optical potential parameters have been extracted from the analysis of the elastic scattering angular distribution. The new potential has been applied to the study of the transfer angular distribution to the 2$^+_2$ 8.32 MeV state in $^{14}$C, using a realistic 3-body $^6$He model and advanced shell model calculations for the carbon structure, allowing to calculate the relative contributions of the simultaneous and sequential two-neutron transfer. The reaction model provides a good description of the 30 MeV data set and shows that the simultaneous process is the dominant transfer mechanism. Sensitivity tests of optical potential parameters show that the final results can be considerably affected by the choice of optical potentials. A reanalysis of data measured previously at 18 MeV however, is not as well described by the same reaction model, suggesting that one needs to include higher order effects in the reaction mechanism.Comment: 9 pages, 9 figure