Investigation of Factors Determining the Enhanced Permeability and Retention Effect in Subcutaneous Xenografts

Liposomal chemotherapy offers several advantages over conventional therapies, including high intratumoral drug delivery, reduced side effects, prolonged circulation time and the possibility to dose higher. The efficient delivery of liposomal chemotherapeutics relies however on the enhanced permeability and retention (EPR) effect, which refers to the ability of macromolecules to extravasate leaky tumor vessels and accumulate in the tumor tissue. Using a panel of human xenograft tumors, we evaluated the influence of the EPR effect on liposomal distribution in vivo by injection of pegylated liposomes radiolabeled with 111In. Liposomal accumulation in tumors and organs was followed over time by SPECT/CT imaging. We observed that fast growing xenografts, which may be less representative of tumor development in patients, showed higher liposomal accumulation as compared to slow growing xenografts. Additionally, several other parameters determining the EPR effect were evaluated, such as blood and lymphatic vessel density, intratumoral hypoxia, and the presence of macrophages. The investigation of various parameters showed a few correlations. Although hypoxia, proliferation and macrophage presence were associated with tumor growth, no hard conclusions or predictions could be made regarding the EPR effect or liposomal uptake. However liposomal uptake was

Wide-field dynamic astronomy in the near-infrared with Palomar Gattini-IR and DREAMS

There have been a dramatic increase in the number of optical and radio transient surveys due to astronomical transients such as gravitational waves and gamma ray bursts, however, there have been a limited number of wide-field infrared surveys due to narrow field-of-view and high cost of infrared cameras, we present two new wide-field near-infrared fully automated surveyors; Palomar Gattini-IR and the Dynamic REd All-sky Monitoring Survey (DREAMS). Palomar Gattini-IR, a 25 square degree J-band imager that begun science operations at Palomar Observatory, USA in October 2018; we report on survey strategy as well as telescope and observatory operations and will also providing initial science results. DREAMS is a 3.75 square degree wide-field imager that is planned for Siding Spring Observatory, Australia; we report on the current optical and mechanical design and plans to achieve on-sky results in 2020. DREAMS is on-track to be one of the first astronomical telescopes to use an Indium Galium Arsenide (InGaAs) detector and we report initial on-sky testing results for the selected detector package. DREAMS is also well placed to take advantage and provide near-infrared follow-up of the LSST

Developing ecosystem service indicators: experiences and lessons learned from sub-global assessments and other initiatives

People depend upon ecosystems to supply a range of services necessary for their survival and well-being. Ecosystem service indicators are critical for knowing whether or not these essential services are being maintained and used in a sustainable manner, thus enabling policy makers to identify the policies and other interventions needed to better manage them. As a result, ecosystem service indicators are of increasing interest and importance to governmental and inter-governmental processes, including amongst others the Convention on Biological Diversity (CBD) and the Aichi Targets contained within its strategic plan for 2011-2020, as well as the emerging Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Despite this growing demand, assessing ecosystem service status and trends and developing robust indicators is o!en hindered by a lack of information and data, resulting in few available indicators. In response, the United Nations Environment Programme World Conservation Monitoring Centre (UNEP-WCMC), together with a wide range of international partners and supported by the Swedish International Biodiversity Programme (SwedBio)*, undertook a project to take stock of the key lessons that have been learnt in developing and using ecosystem service indicators in a range of assessment contexts. The project examined the methodologies, metrics and data sources employed in delivering ecosystem service indicators, so as to inform future indicator development. This report presents the principal results of this project

Optimizing tropical forest bird surveys using passive acoustic monitoring and high temporal resolution sampling

Estimation of avian biodiversity is a cornerstone measure of ecosystem condition. Surveys conducted using autonomous recorders are often more efficient at estimating diversity than traditional point-count surveys. However, there is limited research into the optimal temporal resolution for sampling—the trade-off between the number of samples and sample duration when sampling a survey window with a fixed survey effort—despite autonomous recorders allowing easy repeat sampling compared to traditional survey methods. We assess whether the additional temporal coverage from high temporal resolution (HTR) sampling, consisting of 240 15-s samples spread randomly across a survey window detects higher alpha and gamma diversity than low temporal resolution (LTR) sampling of four 15-min samples at the same locations. We do so using an acoustic dataset collected from 29 locations in a region of very high avian biodiversity—the eastern Brazilian Amazon. We find HTR sampling outperforms LTR sampling in every metric considered, with HTR sampling predicted to detect approximately 50% higher alpha diversity, and 10% higher gamma diversity. This effect is primarily driven by increased coverage of variation in detectability across the morning, with the earliest period containing a distinct community that is often under sampled using LTR sampling. LTR sampling produced almost four times as many false absences for species presence. Additionally, LTR sampling incorrectly found 70 species (34%) at only a single forest type when they were in fact present in multiple forest types, while the use of HTR sampling reduced this to just two species (0.9%). When considering multiple independent detections of species, HTR sampling detected three times more uncommon species than LTR sampling. We conclude that high temporal resolution sampling of passive-acoustic monitoring-based surveys should be considered the primary method for estimating the species richness of bird communities in tropical forests

Neutral and Charged Polymers at Interfaces

Chain-like macromolecules (polymers) show characteristic adsorption properties due to their flexibility and internal degrees of freedom, when attracted to surfaces and interfaces. In this review we discuss concepts and features that are relevant to the adsorption of neutral and charged polymers at equilibrium, including the type of polymer/surface interaction, the solvent quality, the characteristics of the surface, and the polymer structure. We pay special attention to the case of charged polymers (polyelectrolytes) that have a special importance due to their water solubility. We present a summary of recent progress in this rapidly evolving field. Because many experimental studies are performed with rather stiff biopolymers, we discuss in detail the case of semi-flexible polymers in addition to flexible ones. We first review the behavior of neutral and charged chains in solution. Then, the adsorption of a single polymer chain is considered. Next, the adsorption and depletion processes in the many-chain case are reviewed. Profiles, changes in the surface tension and polymer surface excess are presented. Mean-field and corrections due to fluctuations and lateral correlations are discussed. The force of interaction between two adsorbed layers, which is important in understanding colloidal stability, is characterized. The behavior of grafted polymers is also reviewed, both for neutral and charged polymer brushes.Comment: a review: 130 pages, 30 ps figures; final form, added reference

SubHaloes going Notts: The SubHalo-Finder Comparison Project

We present a detailed comparison of the substructure properties of a single Milky Way sized dark matter halo from the Aquarius suite at five different resolutions, as identified by a variety of different (sub-)halo finders for simulations of cosmic structure formation. These finders span a wide range of techniques and methodologies to extract and quantify substructures within a larger non-homogeneous background density (e.g. a host halo). This includes real-space, phase-space, velocity-space and time- space based finders, as well as finders employing a Voronoi tessellation, friends-of-friends techniques, or refined meshes as the starting point for locating substructure.A common post-processing pipeline was used to uniformly analyse the particle lists provided by each finder. We extract quantitative and comparable measures for the subhaloes, primarily focusing on mass and the peak of the rotation curve for this particular study. We find that all of the finders agree extremely well on the presence and location of substructure and even for properties relating to the inner part part of the subhalo (e.g. the maximum value of the rotation curve). For properties that rely on particles near the outer edge of the subhalo the agreement is at around the 20 per cent level. We find that basic properties (mass, maximum circular velocity) of a subhalo can be reliably recovered if the subhalo contains more than 100 particles although its presence can be reliably inferred for a lower particle number limit of 20. We finally note that the logarithmic slope of the subhalo cumulative number count is remarkably consistent and <1 for all the finders that reached high resolution. If correct, this would indicate that the larger and more massive, respectively, substructures are the most dynamically interesting and that higher levels of the (sub-)subhalo hierarchy become progressively less important.Comment: 16 pages, 7 figures, 2 tables, Accepted for MNRA

The evolution of substructure III: the outskirts of clusters

We present an investigation of satellite galaxies in the outskirts of galaxy clusters taken from a series of high-resolution N-body simulations. We focus on the so-called "backsplash population", i.e. satellite galaxies that once were inside the virial radius of the host but now reside beyond it. We find that this population is significant in number and needs to be appreciated when interpreting the various galaxy morphology environmental relationships and decoupling the degeneracy between nature and nurture. Specifically, we find that approximately half of the galaxies with current clustercentric distance in the interval 1-2 virial radii of the host are backsplash galaxies which once penetrated deep into the cluster potential, with 90% of these entering to within 50% of the virial radius. These galaxies have undergone significant tidal disruption, loosing on average 40% of their mass. This results in a mass function for the backsplash population different to those galaxies infalling for the first time. We further show that these two populations are kinematically distinct and should be observable within existent spectroscopic surveys.Comment: 7 pages, 8 figures, MNRAS accepted - minor editing without changing the conclusion

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Institutional logics and interorganizational learning in technological arenas: Evidence from standard-setting organizations in the mobile handset industry

© 2015, INFORMS. Conceptualizing standard-setting organizations (SSOs) as technological arenas within which firms from different countries interact and learn, we offer insights into the interplay between firms' institutional logics and their interorganizational learning outcomes. We suggest that firms' interorganizational learning is embedded in their macrolevel country contexts, characterized by more corporatist versus less corporatist (pluralist) institutional logics. Whereas corporatism spurs coordinated approaches, pluralism engenders competitive interactions that affect the extent to which firms span organizational and technological boundaries and learn from each other. We test our theory using longitudinal analysis of 181 dyads involving 26 firms participating in 17 SSOs in the global mobile handset industry. We find that interorganizational learning, as measured by patent citations, involving corporatist firm dyads significantly increases when the dominant logic within the arena is also corporatist. By making cooperative schemas more accessible, a dominant corporatist logic also enhances interorganizational learning across technologically distant dyads. When a pluralist logic dominates the arena, corporatist dyads learn less because firms in the dyad activate a contradictory logic that decouples them from their natural processes for interorganizational learning. These findings highlight the implications of institutional logics for interorganizational learning outcomes and provide insights into how firms attend to institutional contradictions in arenas that provide opportunities for interorganizational learning

The Double Cover of the Icosahedral Symmetry Group and Quark Mass Textures

We investigate the idea that the double cover of the rotational icosahedral symmetry group is the family symmetry group in the quark sector. The icosahedral (A5) group was previously proposed as a viable family symmetry group for the leptons. To incorporate the quarks, it is highly advantageous to extend the group to its double cover, as in the case of tetrahedral (A4) symmetry. We provide the basic group theoretical tools for flavor model-building based on the binary icosahedral group I' and construct a model of the quark masses and mixings that yields many of the successful predictions of the well-known U(2) quark texture models.Comment: 10 pages, references added, typos in up quark mass matrix correcte