Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo

Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors

Reference values of vessel diameters, stenosis prevalence, and arterial variations of the lower limb arteries in a male population sample using contrast-enhanced MR angiography

Introduction Morphological characterization of leg arteries is of significant importance to detect vascular remodeling triggered by atherosclerotic changes. We determined reference values of vessel diameters and assessed prevalence of stenosis and arterial variations of the lower limb arteries in a healthy male population sample. Methods Gadolinium-enhanced magnetic resonance angiography at 1.5 Tesla was performed in 756 male participants ( median age = 52 years, range = 21 +/- 82 years) of the population-based Study of Health in Pomerania. Vessel diameters were measured in 9 predefined segments of the pelvic and leg arteries and 95th percentiles were used for upper reference values of means of left and right side arteries. Results Reference values of vascular diameters decreased from proximal to distal arteries: common iliac = 1.18cm;internal iliac = 0.75cm;external iliac = 1.03cm;proximal femoral = 1.02cm;distal femoral = 0.77cm;popliteal = 0.69cm;anterior tibial = 0.42cm;posterior tibial = 0.38cm;fibular = 0.40cm. Body-surface area indexed reference values increased with age in all segments. A number of 53 subjects (7.0%) had at least one stenosis, mainly in the lower leg arteries anterior tibial (n = 28, 3.7%), posterior tibial (n = 18, 2.4%) and fibular (n = 20, 2.6%). The risk of stenosis increased considerably with age (odds ratio = 1.08;p<0.001). The most common arterial variant was type I-A in both legs (n = 620, 82%)

A Mutation in LTBP2 Causes Congenital Glaucoma in Domestic Cats (Felis catus)

The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linkage was established on cat chromosome B3 (LOD 18.38, θ = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG identifying a valuable animal model for primary glaucoma that closely resembles the human disease, providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Controlled source electromagnetic measurements offshore the Maltese Islands : implications for offshore freshened groundwater in a carbonate shelf

Carbonate lithologies host considerable quantities of the Earth’s freshwater resources and partially supply a significant amount of the global population with drinkable water. Although they comprise substantial amounts of the coastlines, it is not known if these carbonate lithologies can sustain freshened groundwater offshore, and if this can help meet future water demands in coastal regions. To date, predicting volumes of freshened groundwater within marine carbonates has been challenging. Here, we integrate controlled source electromagnetic profiles with seismic reflection and core log data to derive a lithological model for the eastern carbonate margin of the Maltese Islands, one of the most water-starved countries in the world. Electrical resistivity models are used to guide lithological inference where seismic data provide limited information due to the superimposed seafloor multiple. We show that resistivity values within the Upper Coralline and Globigerina Limestone formations exceed the measured resistivity of seawater-saturated core log samples by at least a factor of four. This could be indicative of offshore freshened groundwater that occupies the pore space of the low permeability limestone along the eastern Maltese shelf. To validate this observation without further ground-truthing data, we use extensive forward modelling to show that a similar resistivity footprint can be achieved by localized interbedded low-porosity or highly cemented units. However, the spatial extent of such units across the entire eastern Maltese margin is geologically improbable. This points to the occurrence of offshore freshened groundwater that was likely emplaced during the last sea-level lowstand.peer-reviewe

Biodiversity post-2020: Closing the gap between global targets and national-level implementation

National and local governments need to step up efforts to effectively implement the post-2020 global biodiversity framework of the Convention on Biological Diversity to halt and reverse worsening biodiversity trends. Drawing on recent advances in interdisciplinary biodiversity science, we propose a framework for improved implementation by national and subnational governments. First, the identification of actions and the promotion of ownership across stakeholders need to recognize the multiple values of biodiversity and account for remote responsibility. Second, cross-sectorial implementation and mainstreaming should adopt scalable and multifunctional ecosystem restoration approaches and target positive futures for nature and people. Third, assessment of progress and adaptive management can be informed by novel biodiversity monitoring and modeling approaches handling the multidimensionality of biodiversity change

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.</p> <p>Methods</p> <p>6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.</p> <p>Results</p> <p>MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm³+/-243 mm³) with MRI (mean 918 mm³+/-193 mm³) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm²+/-22.8 mm²versus 32.6 mm²+/-22.6 mm²(histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm³+/-56.7 mm³after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.</p> <p>Conclusions</p> <p>This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.</p

Scientific opportunies for bERLinPro 2020+, report with ideas and conclusions from bERLinProCamp 2019

The Energy Recovery Linac (ERL) paradigm offers the promise to generate intense electron beams of superior quality with extremely small six-dimensional phase space for many applications in the physical sciences, materials science, chemistry, health, information technology and security. Helmholtz-Zentrum Berlin started in 2010 an intensive R\&D programme to address the challenges related to the ERL as driver for future light sources by setting up the bERLinPro (Berlin ERL Project) ERL with 50 MeV beam energy and high average current. The project is close to reach its major milestone in 2020, acceleration and recovery of a high brightness electron beam. The goal of bERLinProCamp 2019 was to discuss scientific opportunities for bERLinPro 2020+. bERLinProCamp 2019 was held on Tue, 17.09.2019 at Helmholtz-Zentrum Berlin, Berlin, Germany. This paper summarizes the main themes and output of the workshop