Dilations and information flow axioms in categorical probability

We study the positivity and causality axioms for Markov categories as properties of dilations and information flow in Markov categories, and in variations thereof for arbitrary semicartesian monoidal categories. These help us show that being a positive Markov category is merely an additional property of a symmetric monoidal category (rather than extra structure). We also characterize the positivity of representable Markov categories and prove that causality implies positivity, but not conversely. Finally, we note that positivity fails for quasi-Borel spaces and interpret this failure as a privacy property of probabilistic name generation.Comment: 42 page

Pathogenesis of lassa fever in cynomolgus macaques

<p>Abstract</p> <p>Background</p> <p>Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.</p> <p>Methods</p> <p>Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.</p> <p>Results</p> <p>Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.</p> <p>Conclusion</p> <p>The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.</p

In vitro and in silico assessment of flow modulation after deploying the Contour Neurovascular System in intracranial aneurysm models

Background The novel Contour Neurovascular System (Contour) has been reported to be efficient and safe for the treatment of intracranial, wide-necked bifurcation aneurysms. Flow in the aneurysm and posterior cerebral arteries (PCAs) after Contour deployment has not been analyzed in detail yet. However, this information is crucial for predicting aneurysm treatment outcomes. Methods Time-resolved three-dimensional velocity maps in 14 combinations of patient-based basilar tip aneurysm models with and without Contour devices (sizes between 5 and 14 mm) were analyzed using four-dimensionsal (4D) flow MRI and numerical/image-based flow simulations. A complex virtual processing pipeline was developed to mimic the experimental shape and position of the Contour together with the simulations. Results On average, the Contour significantly reduced intra-aneurysmal flow velocity by 67% (mean w/ = 0.03m/s; mean w/o = 0.12m/s; p-value=0.002), and the time-averaged wall shear stress by more than 87% (mean w/ = 0.17Pa; mean w/o = 1.35Pa; p-value=0.002), as observed by numerical simulations. Furthermore, a significant reduction in flow (P<0.01) was confirmed by the neck inflow rate, kinetic energy, and inflow concentration index after Contour deployment. Notably, device size has a stronger effect on reducing flow than device positioning. However, positioning affected flow in the PCAs, while being robust in effectively reducing flow. Conclusions This study showed the high efficacy of the Contour device in reducing flow within aneurysms regardless of the exact position. However, we observed an effect on the flow in PCAs, which needs to be investigated further

A novel role for NUAK1 in promoting ovarian cancer metastasis through regulation of fibronectin production in Spheroids

Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabilization. We next investigated NUAK1 function in EOC cells. Ectopic NUAK1-overexpressing EOC cell lines had increased adhesion, whereas the reverse was seen in OVCAR8-NUAK1KO cells. In fact, cells with NUAK1 loss generate spheroids with reduced integrity, leading to increased cell death after long-term culture. Following transcriptome analysis, we identified reduced enrichment for cell interaction gene expression pathways in OVCAR8-NUAK1KO spheroids. In fact, the FN1 gene, encoding fibronectin, exhibited a 745-fold decreased expression in NUAK1KO spheroids. Fibronectin expression was induced during native spheroid formation, yet this was completely lost in NUAK1KO spheroids. Co-incubation with soluble fibronectin restored the compact spheroid phenotype to OVCAR8-NUAK1KO cells. In a xenograft model of intraperitoneal metastasis, NUAK1 loss extended survival and reduced fibronectin expression in tumours. Thus, we have identified a new mechanism controlling EOC metastasis, through which LKB1-NUAK1 activity promotes spheroid formation and secondary tumours via fibronectin production

First pan-Arctic assessment of dissolved organic carbon in lakes of the permafrost region

Lakes in permafrost regions are dynamiclandscape components and play an important role for climatechange feedbacks. Lake processes such as mineralizationand flocculation of dissolved organic carbon (DOC), oneof the main carbon fractions in lakes, contribute to thegreenhouse effect and are part of the global carbon cycle.These processes are in the focus of climate research, butstudies so far are limited to specific study regions. Inour synthesis, we analyzed 2167 water samples from 1833lakes across the Arctic in permafrost regions of Alaska,Canada, Greenland, and Siberia to provide first pan-Arcticinsights for linkages between DOC concentrations andthe environment. Using published data and unpublisheddatasets from the author team, we report regional DOCdifferences linked to latitude, permafrost zones, ecoregions,geology, near-surface soil organic carbon contents, andground ice classification of each lake region. The lakeDOC concentrations in our dataset range from 0 to1130 mg L−1(10.8 mg L−1median DOC concentration).Regarding the permafrost regions of our synthesis, wefound median lake DOC concentrations of 12.4 mg L−1(Siberia), 12.3 mg L−1(Alaska), 10.3 mg L−1(Greenland),and 4.5 mg L−1(Canada). Our synthesis shows a significantrelationship between lake DOC concentration and lakeecoregion. We found higher lake DOC concentrationsat boreal permafrost sites compared to tundra sites. Wefound significantly higher DOC concentrations in lakesin regions with ice-rich syngenetic permafrost deposits(yedoma) compared to non-yedoma lakes and a weak butsignificant relationship between soil organic carbon contentand lake DOC concentration as well as between ground icecontent and lake DOC. Our pan-Arctic dataset shows that theDOC concentration of a lake depends on its environmentalproperties, especially on permafrost extent and ecoregion, aswell as vegetation, which is the most important driver of lakeDOC in this study. This new dataset will be fundamental toquantify a pan-Arctic lake DOC pool for estimations of theimpact of lake DOC on the global carbon cycle and climatechange

Development of a New Vaccine for the Prevention of Lassa Fever

BACKGROUND: Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge. METHODS AND FINDINGS: We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection. CONCLUSION: Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease

The Slowing Gulf Stream? What we know and potential impacts (Policy Brief)

Blue-Action aims to improve our ability to describe, model, and predict Arctic climate change and its impact on Northern Hemisphere climate, weather, and their extremes, and to deliver valuated climate services of societal benefit. Blue-Action contributes to the implementation of the Trans-Atlantic Ocean Research Alliance, to the EU’s Blue Growth Agenda, and to a long-term strategy to support sustainable growth in the marine and maritime sectors as a whole. Blue-Action supports the implementation of the Galway and the Belem Statements and the achievement of UN SDG 8, 9, 13