A heterotic sigma model with novel target geometry

We construct a (1,2) heterotic sigma model whose target space geometry consists of a transitive Lie algebroid with complex structure on a Kaehler manifold. We show that, under certain geometrical and topological conditions, there are two distinguished topological half--twists of the heterotic sigma model leading to A and B type half--topological models. Each of these models is characterized by the usual topological BRST operator, stemming from the heterotic (0,2) supersymmetry, and a second BRST operator anticommuting with the former, originating from the (1,0) supersymmetry. These BRST operators combined in a certain way provide each half--topological model with two inequivalent BRST structures and, correspondingly, two distinct perturbative chiral algebras and chiral rings. The latter are studied in detail and characterized geometrically in terms of Lie algebroid cohomology in the quasiclassical limit.Comment: 83 pages, no figures, 2 references adde

Electromagnetic Actuated stirring in Microbioreactors enabling easier multiplexing & flexible device design

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The development of a novel electromagnetically (EM) actuated stirring method, for use in microbioreactors, is reported. Mixing in microbioreactors is critical to ensure even distribution of nutrients to microorganisms and cells. Magnetically driven stirrer bars or peristaltic mixing are the most commonly utilised mixing methods employed in completely liquid-filled microbioreactors. However the circular reactor shape required for mixing with a stirrer bar and frequently used for peristaltically mixed microbioreactors presents difficulties for bubble-free priming in a microfluidic bioreactor. Moreover the circular shape and the hardware required for both types of mixing reduces the potential packing density of multiplexed reactors. We present a new method of mixing, displaying design flexibility by demonstrating mixing in circular and diamond-shaped reactors and a duplex diamond reactor and fermentation of the gram-positive bacteria S. carnosus in a diamond-shaped microbioreactor system. The results of the optimisation of this mixing method for performing fermentations alongside both batch and continuous culture fermentations are presented

Identifying Improved Sites for Heterologous Gene Integration Using ATAC-seq

Constructing efficient cellular factories often requires integration of heterologous pathways for synthesis of novel compounds and improved cellular productivity. Few genomic sites are routinely used, however, for efficient integration and expression of heterologous genes, especially in nonmodel hosts. Here, a data-guided framework for informing suitable integration sites for heterologous genes based on ATAC-seq was developed in the nonmodel yeast Komagataella phaffii. Single-copy GFP constructs were integrated using CRISPR/Cas9 into 38 intergenic regions (IGRs) to evaluate the effects of IGR size, intensity of ATAC-seq peaks, and orientation and expression of adjacent genes. Only the intensity of accessibility peaks was observed to have a significant effect, with higher expression observed from IGRs with low- to moderate-intensity peaks than from high-intensity peaks. This effect diminished for tandem, multicopy integrations, suggesting that the additional copies of exogenous sequence buffered the transcriptional unit of the transgene against effects from endogenous sequence context. The approach developed from these results should provide a basis for nominating suitable IGRs in other eukaryotic hosts from an annotated genome and ATAC-seq data

The skinny on CCN2

The CCN family of matricellular proteins directly or indirectly affects development and differentiation. A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740–C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations

The antidiabetic effects of a dry powder of dietary vegetable and fruit mixtures in diabetic db/db mice

We evaluated the antidiabetic effects of a mixed vegetable powder-formula I (MVP-FI), which is a dry powder mixture of over 65 kinds of vegetables and fruits, using the db/db type 2 diabetes mouse model. The db/db mice at 8-10 weeks of age were randomly divided into three groups: vehicle treatment, 1.575 g/kg MVP-FI treatment, and 3.15 g/kg MVP-FI treatment. During 12 days of treatment, we measured food intake and body weight changes, fasting blood glucose levels, and plasma lipid levels. Our results showed that the food intake and the body weight of MVP-FI-treated group were decreased gradually. Moreover, the fasting blood glucose level of the treated group was significantly dropped to a normal level comparable to that of the lean mice. Furthermore, we also found that the plasma triglyceride level in the treated group was dropped, whereas the high-density lipoprotein (HDL) level was increased and total cholesterol/HDL-cholesterol ratio was decreased. Taken together, these results suggest that the diabetic conditions of the db/db mice have been improved after 12 days treatment with MVP-FI. The antihyperglycemic and antiobese activities of the MVP-FI, as demonstrated in the present study, may have important clinical implications for improving the management of type 2 diabetic patients. © 2008 Yeung et al, publisher and licensee Dove Medical Press Ltd.published_or_final_versio

Imaging the Black Hole Silhouette of M87: Implications for Jet Formation and Black Hole Spin

The silhouette cast by the horizon of the supermassive black hole in M87 can now be resolved with the emerging millimeter very-long baseline interferometry (VLBI) capability. Despite being ~2000 times farther away than SgrA* (the supermassive black hole at the center of the Milky-Way and the primary target for horizon-scale imaging), M87's much larger black hole mass results in a horizon angular scale roughly half that of SgrA*'s, providing another practical target for direct imaging. However, unlike SgrA*, M87 exhibits a powerful radio jet, providing an opportunity to study jet formation physics on horizon scales. We employ a simple, qualitatively correct force-free jet model to explore the expected high-resolution images of M87 at wavelengths of 1.3mm and 0.87mm (230GHz and 345GHz), for a variety of jet parameters. We show that future VLBI data will be able to constrain the size of the jet footprint, the jet collimation rate, and the black hole spin. Polarization will further probe the structure of the jet's magnetic field and its effect on the emitting gas. Horizon-scale imaging of M87 and SgrA* will enable for the first time the empirical exploration of the relationship between the mass and spin of a black hole and the characteristics of the gas inflow/outflow around it.Comment: 18 pages, 7 figures, accepted by Ap

Oral drug delivery strategies for development of poorly water soluble drugs in paediatric patient population

Selecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulations. However, there is paucity of available literature for selection of technology and overcoming the challenges in paediatric formulation development. The need for flexible dosing, and the limited knowledge of the safety of many formulation excipients in paediatric subjects, impose significant constraints and in some instances require adaptation of the approaches taken to formulating these drugs for the adult population. Selection of the best drug delivery system for paediatrics requires an efficient, systematic approach that considers a drug's physical and chemical properties and the targeted patient population's requirements. This review is a step towards development of a strategy for the design of solubility enhancing paediatric formulations of highly insoluble drugs. The aim of this review is to provide an overview of different approaches and strategies to consider in order to assist development of paediatric formulation for poorly water-soluble drugs with the provision of examples of some marketed products. In addition, it provides recommendations to overcome the range of challenges posed by these strategies and adaptations of the adult approach/product presentation required to enable paediatric drug development and administration

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

Projections of the healthcare costs and disease burden due to hepatitis C infection under different treatment policies in Malaysia, 2018-2040

The World Health Organisation (WHO) has set ambitious goals to reduce the global disease burden associated with, and eventually eliminate, viral hepatitis