Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases

On Glauber modes in Soft-Collinear Effective Theory

Gluon interactions involving spectator partons in collisions at hadronic machines are investigated. We find a class of examples in which a mode, called Glauber gluons, must be introduced to the effective theory for consistency.Comment: 19 pages, three figures. Uses JHEP3.cl

An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib

BACKGROUND: Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. PATIENTS AND METHODS: Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers. RESULTS: Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts. CONCLUSIONS: The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. CLINICAL TRIAL NUMBER: NCT00777582 (ClinicalTrials.gov

An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib

BACKGROUND: Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. PATIENTS AND METHODS: Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers. RESULTS: Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts. CONCLUSIONS: The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. CLINICAL TRIAL NUMBER: NCT00777582 (ClinicalTrials.gov

Alternative low-cost adsorbent for water and wastewater decontamination derived from eggshellwaste: an overview

As the current global trend towards more stringent environmental standards, technical applicability and cost-effectiveness became key factors in the selection of adsorbents for water and wastewater treatment. Recently, various low-cost adsorbents derived from agricultural waste, industrial by-products or natural materials, have been intensively investigated. In this respect, the eggshells from egg-breaking operations constitute significant waste disposal problems for the food industry, so the development of value-added by-products from this waste is to be welcomed. The egg processing industry is very competitive, with low profit margins due to global competition and cheap imports. Additionally, the costs associated with the egg shell disposal (mainly on landfill sites) are significant, and expected to continue increasing as landfill taxes increase. The aim of the present review is to provide an overview on the development of low-cost adsorbents derived from eggshell by-products

Dark Radiation and Dark Matter in Large Volume Compactifications

We argue that dark radiation is naturally generated from the decay of the overall volume modulus in the LARGE volume scenario. We consider both sequestered and non-sequestered cases, and find that the axionic superpartner of the modulus is produced by the modulus decay and it can account for the dark radiation suggested by observations, while the modulus decay through the Giudice-Masiero term gives the dominant contribution to the total decay rate. In the sequestered case, the lightest supersymmetric particles produced by the modulus decay can naturally account for the observed dark matter density. In the non-sequestered case, on the other hand, the supersymmetric particles are not produced by the modulus decay, since the soft masses are of order the heavy gravitino mass. The QCD axion will then be a plausible dark matter candidate.Comment: 27 pages, 4 figures; version 3: version published in JHE

A Novel Laser Vaccine Adjuvant Increases the Motility of Antigen Presenting Cells

Background Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. Methodology/Principal Findings We found that laser at a specific setting increased the motility of antigen presenting cells (APCs) and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA) effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d.) or intramuscular (i.m.) administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag)-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag+ dendritic cells (DCs) in draining lymph nodes was significantly higher in both the 1° and 2° draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA) or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone. Conclusion/Significance The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants.National Institutes of Health (U.S.) (grant AI070785)National Institutes of Health (U.S.) (grant RC1 DA028378)Bill & Melinda Gates Foundation (Grand Challenges Explorations grant # 53273)Boston BioCom (Firm) (Sponsored Research agreement grant #2008A25652

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure