The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model

BACKGROUND Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis. METHODS Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups. RESULTS A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed. CONCLUSIONS The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL1

Determination of habitat requirements of the glacial relict Nuphar pumila as basis for successful (re-)introductions

Nuphar pumila is a glacial relict, which is nowadays rare throughout Europe and red-listed in most European regions. In Switzerland only three autochthonous populations and one population of the hybrid with N. lutea (N. ×spenneriana) have survived to date, one of them in the canton of Zurich. To protect this species regionally, the canton of Zurich has commissioned the ex situ propagation of speci-mens, which then had been introduced to 37 water bodies in protected areas, including one known former site. Since only about 10% of these introductions had been successful, there was a wish to identify causes of this lack of success. To this end, we compared the vegetation and physical-chemical parameters of the four natural sites in Switzerland with the successful and unsuccessful introduction sites. Additionally, for a subset of sites, we assessed diatom genus composition as a proxy of water quality. Moreover, we derived vegetation plots of N. pumila and N. lutea from across Europe from the European Vegetation Archive (EVA) to compare their site conditions, using mean ecological indicator values and bioclimatic variables of the localities. We found that inside Switzerland the main differences were between the natural sites and all introduction sites, while successful and unsuccessful introduction sites hardly differed in the determined parameters. Natural sites had cooler water with lower magnesi-um content, and according to mean ecological indicator values, also lower nutrient status. The diatom data, though limited in amount, point into the same direction. The EVA data demonstrate that stands of N. pumila are mainly more oligotrophic, but also cooler and more acidic than those of N. lutea. We could not find any factor that explains the success vs. lack of success of plantations of N. pumila in multiple sites in the canton of Zurich, but our results rather indicate that due to the relatively warm climate, the high atmogenic nitrogen input and the predominantly base-rich bedrock, the sites in the canton are generally not particularly well suited for N. pumila. We consider it therefore more promising to protect and possibly (re-)introduce N. pumila in other cantons with higher elevation, base-poor bedrock and lower atmogenic nitrogen input

The impact of tumor metabolic activity assessed by 18^{18}F-FET amino acid PET imaging in particle radiotherapy of high-grade glioma patients

Selective uptake of (18)F-fluoro-ethyl-tyrosine ($^{18}$F-FET) is used in high-grade glioma (HGG) to assess tumor metabolic activity via positron emission tomography (PET). We aim to investigate its value for target volume definition, as a prognosticator, and associations with whole-blood transcriptome liquid biopsy (WBT lbx) for which we recently reported feasibility to mirror tumor characteristics and response to particle irradiation in recurrent HGG (rHGG)

Selecting teachers and prospective teachers : a meta-analysis

The purpose of this review article was to examine the methods used for the selection of teachers for employment and prospective teachers entering initial teacher education (ITE) programs, and to assess the predictive validity of these methods. We reviewed 32 studies reporting selection methods administered in high-stakes conditions and that included an external (not self-reported) teacher effectiveness outcome measure. The overall effect size was small but significant (r = 0.12, p <.001). Moderator analyses showed that academic and non-academic predictors were both significantly associated with teacher effectiveness measures and that effect sizes were small (but significant) for selection into employment and ITE. We conclude the review by proposing a research agenda that has the potential to enhance educational outcomes by improving the selection of prospective teachers

Applicability of Standard Photovoltaic Modules for an Increased Share of Renewable Energies on Board Cruise Ships Applicability of Standard Photovoltaic Modules for an Increased Share of Renewable Energies on Board Cruise Ships

The aim of this study is to evaluate the potential of using standard photovoltaic (PV) modules on board of cruise ships to increase the share of renewable energies in the total energy demand. Due to the limited space available, also partial shaded areas must be considered for installation. As a large part of the ship hull is covered by cabin balconies, this area is of particular interest. An analysis for a clear sky scenario will be carried out based on a simulation, which reflects the solar irradiation on these areas during a representative cruise

Yield Calculations of a PV System Integrated in Cruise Ships: A Case Study in the Waters of the Caribbean

Facing the problem of air and marine pollution, the shipping industry has shown a rising interest in developing low-emission vessels. Passenger cruise ships i.e. make a particular contribution to the deterioration of air quality, not only in port areas but also in open waters. The implementation of renewable technologies is considered as an important solution. In this study a method is reported which allows yield calculations of a photovoltaic system integrated in cruise ship balconies. Geographic, atmospheric and structural aspects are considered in the simulation. The latter also involves the very variable shading due to the ships movement. On the basis of a conceptual PV system, first results for a 14-day cruise in the Caribbean Sea are presented. These indicate a solar energy yield in the GWh range, considering a cruiser with more than 2000 cabin balconies

Review of local in situ probing techniques for the interfaces of lithium-ion and lithium-oxygen batteries

Electrodes in lithium-ion and post-lithium-ion batteries are made of composite materials exposing a variety of different surfaces towards the electrolyte. This causes a distribution of current densities and consequently locally different changes of interfaces and bulk materials that might be critical for the performance and durability of secondary batteries. The optimization of local structures of battery materials is hindered by a lack of local techniques that provide in situ reactivity information from such hidden interfaces. A variety of new electrochemical scanning probe techniques are currently adapted to the investigation of battery materials under near-realistic environmental conditions. The review provides a critical assessment of this development with a particular emphasis on the assessment of the passivating properties of solid–electrolyte interphases, the extension of the concepts to lithium–oxygen cells, and attempts to image ion intercalation reactions

p37/UBXN2B regulates spindle orientation by limiting cortical NuMA recruitment via PP1/Repo-Man

Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi-LGN-NuMA complex, which targets the force generator dynein-dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Gαi, the kinase Aurora A, and the phosphatase PP2A. Our data show that in anaphase, when the spindle elongates, PP1/Repo-Man promotes the accumulation of NuMA at the cortex. In metaphase, p37 negatively regulates this function of PP1, resulting in lower cortical NuMA levels and correct spindle orientation