Magnetic North, Pyramiden, Svalbard

excerpts from Magnetic North Pyramiden, Svalbar

Branches Over Ripples: A Waterside Journal by Brian Bartlett

Review of Brian Bartlett\u27s Branches Over Ripples: A Waterside Journa

Using Cellular Automata and Lattice Boltzmann Methods to Model Cancer Growth: Analysis of Combination Treatment Outcomes

In Canada it is estimated that 76,600 people will die of cancer in 2014. Cancer, a collection of over 200 diseases, has differences existing between globally, between individuals and overtime in one individual. Treatment options are similarly varied. These differences make selecting the best possible treatment for every type of cancer very challenging. In addition, with no single cure for cancer, treatments are often combined in different ways to form the best overall option. In an attempt to synthesize the properties of these diseases into a collection of common cellular changes, Hanahan and Weinberg proposed ``the hallmarks of cancer -- 10 differences between healthy cells and cancer cells, present in almost every cancer. There exists the potential for treatments that are broadly applicable if they reverse these general properties. This work seeks to simulate early cancer growth, specifically looking at these hallmarks, and detect the best combinations of hallmarks to remove in order to stop cancer growth. This hybrid simulation combines a discrete model of cancer cells using cellular automata, with a continuous model of blood flow using lattice Boltzmann methods. Hallmarks relevant during the early growth stages of solid tumour development are simulated using rules in the cellular automata. Hallmarks were removed in pairs, triplets and quadruplets in order to model combination therapy, abstracting drugs that target these properties as the removal of the hallmark from the system. Overall growth of the tumours with ``treatments applied were compared to tumours where all hallmarks were present. It was found that many combinations had no effect on tumour growth. In some cases combinations even increased growth, selecting for the most aggressive hallmarks since weaker hallmarks were unavailable. However, in general, as more treatments were applied, cancer growth decreased. This work is the first to simulate removing hallmarks in pairs, triplets and quadruplets from a model with biologically relevant oxygen flow. It provides a proof of concept that not all combinations are equally effective, even if the individual treatments are effective. This work suggests some combinations should be avoided while others could potentially be beneficial in a variety of diseases

Stray Thoughts and Desire Paths—A Dialogue

In this dialogue, authors, teachers, and environmentalists Yvonne Blomer and Jenna Butler discuss the ways in which our desire paths—our intents for our lives—have changed since the start of the pandemic. Covering women\u27s writing, feminism, daily life during the pandemic, environmentalism, and race, this dialogue is an act of allyship from two women of different backgrounds writing together

Halting the hallmarks: a cellular automaton model of early cancer growth inhibition

Cancer treatment is a fragmented and varied process, as ‘‘cancer’’ is really hundreds of different diseases. The ‘‘hallmarks of cancer’’ proposed by Hanahan and Weinberg (Cell 100(1):57–70, 2000) are a framework for viewing cancer within a common set of underlying principles—ten properties that are common to almost all cancers, allowing them to grow uncontrollably and ravage the body. We used a cellular automaton model of tumour growth paired with lattice Boltzmann methods modelling oxygen flow to simulate combination drugs targeted at knocking out pairs of hallmarks. We found that knocking out some pairs of cancer-enabling hallmarks did not prevent tumour formation, while other pairs significantly prevent tumour growth (p ¼ 0:0004 using Wilcoxon signed-rank adjusted with the Bonferroni correction for multiple comparisons). This is not what would be expected from models of knocking out the hallmarks individually, as many pairs did not have an additive effect but had either no statistically significant effect or a multiplicative one. We propose that targeting certain pairs of cancer hallmarks, specifically cancers ability to induce blood vessel development paired with another cancer hallmark, could prove an effective cancer treatment option

HD-CNV: hotspot detector for copy number variants.

SUMMARY: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software or by automated graph analysis, is useful in identifying genomic regions of interest for further study. AVAILABILITY AND IMPLEMENTATION: HD-CNV is an open source Java code and is freely available, with tutorials and sample data from http://daleylab.org. CONTACT: [email protected]

PD-1 Co-inhibitory and OX40 Co-stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity

SummaryThe differentiation and protective capacity of Plasmodium-specific T cells are regulated by both positive and negative signals during malaria, but the molecular and cellular details remain poorly defined. Here we show that malaria patients and Plasmodium-infected rodents exhibit atypical expression of the co-stimulatory receptor OX40 on CD4 T cells and that therapeutic enhancement of OX40 signaling enhances helper CD4 T cell activity, humoral immunity, and parasite clearance in rodents. However, these beneficial effects of OX40 signaling are abrogated following coordinate blockade of PD-1 co-inhibitory pathways, which are also upregulated during malaria and associated with elevated parasitemia. Co-administration of biologics blocking PD-1 and promoting OX40 signaling induces excessive interferon-gamma that directly limits helper T cell-mediated support of humoral immunity and decreases parasite control. Our results show that targeting OX40 can enhance Plasmodium control and that crosstalk between co-inhibitory and co-stimulatory pathways in pathogen-specific CD4 T cells can impact pathogen clearance