Models for drug absorption from the small intestine: where are we and where are we going?

The small intestine is a complex organ with movements, flora, mucus and flows. Despite this, the most widely used absorption models consider the organ a cylindrical monoepithelial tube. This review presents the recent evolution of models to take into consideration the complex nature of gut physiology. The most commonly encountered issues are ethical (in vivo models) and differences in drug transport as a result of a modified expression of drug transporters or metabolic enzymes compared with human (in vitro and in vivo models). Finally, this review discusses the way forward to reach an ideal equilibrium between reproducibility, predictability and efficiency for predicting permeability. The features of an ideal model are listed as a guideline for future development

Pamela: development of the RF system for a non-relativistic non-scaling FFAG

The PAMELA project(Particle Accelerator For MEdical Applications) currently consists of the design of a particle therapy facility. The project, which is in the design phase, contains Non-Scaling FFAG, particle accelerator capable of rapid beam acceleration, giving a pulse repetition rate of 1kHz, far beyond that of a conventional synchrotron. To realise the repetition rate, a key component of the accelerator is the rf accelerating system. The combination of a high energy gain per turn and a high repetition rate is a significant challenge. In this paper, options for the rf system of the proton ring and the status of development are presented

COVID-19 rapidly increases MDSCs and prolongs innate immune dysfunctions.

We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID-19 induces a rapid, transient upregulation of myeloid-derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID-19 patients

Two-magnon Raman scattering in insulating cuprates: Modifications of the effective Raman operator

Calculations of Raman scattering intensities in spin 1/2 square-lattice Heisenberg model, using the Fleury-Loudon-Elliott theory, have so far been unable to describe the broad line shape and asymmetry of the two magnon peak found experimentally in the cuprate materials. Even more notably, the polarization selection rules are violated with respect to the Fleury-Loudon-Elliott theory. There is comparable scattering in $B_{1g}$ and $A_{1g}$ geometries, whereas the theory would predict scattering in only $B_{1g}$ geometry. We review various suggestions for this discrepency and suggest that at least part of the problem can be addressed by modifying the effective Raman Hamiltonian, allowing for two-magnon states with arbitrary total momentum. Such an approach based on the Sawatzsky-Lorenzana theory of optical absorption assumes an important role of phonons as momentum sinks. It leaves the low energy physics of the Heisenberg model unchanged but substantially alters the Raman line-shape and selection rules, bringing the results closer to experiments.Comment: 7 pages, 6 figures, revtex. Contains some minor revisions from previous versio

Preliminary Heat Capacity and Vapor Pressure Measurements of 2D 4He on ZYX Graphite

We report preliminary heat capacity and vapor pressure measurements of the first and second layers of 4He adsorbed on ZYX graphite. ZYX is known to have much better crystallinity than Grafoil, the most commonly-used exfoliated graphite substrate, such as a ten-times larger platelet size. This allows us to distinguish different phases in 2D helium-4 much more clearly and may provide qualitatively different insights into this system. We found a significantly asymmetric density-dependence of the heat-capacity peak associated with the 1/3 phase formation comparing with that obtained with Grafoil. The 2nd-layer promotion density is determined as 11.8+-0.3 nm-2 from the heat-capacity measurement of low density samples in the 2nd layer and vapor pressure measurement.Comment: 7 pages, 7 figures, accepted for publication in JLTP - QFS201

Allaeochelys libyca, a new carettochelyine turtle from the middle miocene (Langhian) of Libya

Fossil carettochelyine turtles are well known from the Paleogene of Europe (Allaeochelys), North America and Asia (Anosteira); however, the previously known Neogene fossil record is highly fragmentary and was therefore unsuitable for taxonomic analysis. In this work, we present a new carettochelyine taxon, Allaeochelys libyca, from the Middle Miocene (Langhian) of Gebel Zelten (Libya) based on an incomplete skull and disarticulated postcranial elements. The new taxon is diagnosed relative to the extant Carettochelys insculpta based on the placement of the foramen posterius canalis carotici interni close to the fenestra postotica, the horizontal orientation of the tubercula basioccipitalis, the substantial contribution of the opisthotic to the base of the tubercula basioccipitalis, the presence of a triangular pterygoid fossa, the arrangement of the mandibular condyles along a plane and the presence of an extremely well-developed fossa at the base of the processus mandibularis. A phylogenetic analysis of pancarettochelyids confirms the monophyly of Carettochelyidae and Carettochelyinae but resulted in a paraphyletic taxon, Allaeochelys. For the sake of nomenclatural stability, we provisionally retain the genus Allaeochelys as paraphyletic relative to the extant Carettochelys insculpta

A systematic SNP selection approach to identify mechanisms underlying disease aetiology: Linking height to post-menopausal breast and colorectal cancer risk

Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values < 1 × 10-5 and a genomic sliding window of 1 mega base pair, we identified SNP clusters including at least one SNP associated with height and one SNP associated with either post-menopausal BC or CRC risk (or both). SNPs were annotated to genes using HapMap and GRAIL and analysed for significantly overrepresented pathways using ConsensuspathDB. Twelve clusters including 56 SNPs annotated to 26 genes were prioritised because these included at least one height- and one BC risk- or CRC risk-associated SNP annotated to the same gene. Annotated genes were involved in Indian hedgehog signalling (p-value = 7.78 × 10-7) and several cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC

Orbital-selective Mott transitions: Heavy fermions and beyond

Quantum phase transitions in metals are often accompanied by violations of Fermi liquid behavior in the quantum critical regime. Particularly fascinating are transitions beyond the Landau-Ginzburg-Wilson concept of a local order parameter. The breakdown of the Kondo effect in heavy-fermion metals constitutes a prime example of such a transition. Here, the strongly correlated f electrons become localized and disappear from the Fermi surface, implying that the transition is equivalent to an orbital-selective Mott transition, as has been discussed for multi-band transition-metal oxides. In this article, available theoretical descriptions for orbital-selective Mott transitions will be reviewed, with an emphasis on conceptual aspects like the distinction between different low-temperature phases and the structure of the global phase diagram. Selected results for quantum critical properties will be listed as well. Finally, a brief overview is given on experiments which have been interpreted in terms of orbital-selective Mott physics.Comment: 29 pages, 4 figs, mini-review prepared for a special issue of JLT

Seismic structure across the rift valley of the Mid-Atlantic Ridge at 23°20′ (MARK area): Implications for crustal accretion processes at slow spreading ridges

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