Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

AbstractQuantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRI)R1 mapping with diffusionbased multispectral (MS) analysis is introduced. This approach restricts the partial pressure of oxygen (pO2) measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1) and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980). GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment

Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity

The Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA)

To explore the various couplings across space and time and between ecosystems in a consistent manner, atmospheric modeling is moving away from the fractured limited-scale modeling strategy of the past toward a unification of the range of scales inherent in the Earth system. This paper describes the forward-looking Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA), which is intended to become the next-generation community infrastructure for research involving atmospheric chemistry and aerosols. MUSICA will be developed collaboratively by the National Center for Atmospheric Research (NCAR) and university and government researchers, with the goal of serving the international research and applications communities. The capability of unifying various spatiotemporal scales, coupling to other Earth system components, and process-level modularization will allow advances in both fundamental and applied research in atmospheric composition, air quality, and climate and is also envisioned to become a platform that addresses the needs of policy makers and stakeholders

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Rapid Processes for Educational Resource Creation

The technology used for teaching is an expanding, integrated set of electronic resources. In each curricular area, there is potential to create a wealth of online educational materials, but often that material creation is time-intensive. For example, producing quality video may take 50-100 hours of work to create one hour of finished video- even more if captions are created. Recently, we worked with students who have special needs. The students required materials we did not have, and did not have the time or funds to order. So, we created rapid processes for educational material creation that could ultimately be used for all students. The two processes we worked on were: creating 3D renderings of graphed data, and streamlining a process to create video transcriptions. Our 3D graphing method relies on color shades to process graph components into different heights which can then be printed. Using this color method, we were able to decrease our creation and processing time from 4 hours to only about half an hour. For the video transcription/captions, we created the video normally, then used a crossover cable and free speech-to-text tool to automatically transcribe the voice in the video. Limited editing for elements such as punctuation and word correction was required following the automatic transcription. This editing process took a fraction of the time normally required to transcribe previous videos

Digital Textbook Delivery: Options and Effectiveness

In response to textbook cost legislation, and to better prepare current college of education students for the textbooks that they will have to use with their students, a prerequisite course on educational technology integrated an open source digital textbook. Textbooks have, for many students, become large (and expensive) compendiums of material that students seldom read, study from or even enjoy, as evidenced by research showing that student reading of assigned textbooks is in an overall decline from previous years (Burchfield & Sappington 2000, Connor-Greene 2000, Sikorski et al. 2001). The overall goal of this study is to find effective ways to improve the rates of enrichment textbook reading for an undergraduate course. This presentation will described the baseline research findings of a study investigating textbook reading amounts and delivery formats for undergraduates students taking an introductory educational technology course. Initial findings include information concerning digital textbook reading with smart phone, tablet, and ebook reading device, ownership rates, low digital textbook usage outside of the researched course, and student preferences concerning electronic textbook reading features such as highlighting, note taking and portability