Single Event Effects Testing For Low Earth Orbit Missions with Neutrons

Neutrons can effectively be used to screen electronic parts intended to be used in Low Earth Orbit. This paper compares neutron with proton environments in spacecraft and discusses recent comparison testing

Vascular Alteration with Postural Change as Observed Using the Anterior Tibial Artery: A Pilot Study

Plantar fasciopathy and plantar fasciosis are common lower extremity conditions. Vascular health is an important aspect of plantar fascia health. Footwear choices are thought to influence lower extremity vascular flow, but how the anterior tibial artery is affected by purely postural changes over time is unknown. PURPOSE: To observe the anterior tibial artery vascular alterations over a ten-minute period after transitioning from a sitting to a standing position while barefoot. METHODS: Nine participants (age= 23.8yrs ±2.5, height= 176.0cm ±8.0, weight= 69.8kg ±10.2) were recruited from Brigham Young University for a single 30-minute visit. The participants had no previous lower extremity injuries within 6 months. The individual’s dominant foot arch height index was recorded, and the participant had a 3-lead ECG placed on their trunk. A Logic Fortis machine with an L8-18i probe was used to capture pulse wave (PW) images of the anterior tibial artery of the dominant foot. The participant sat barefoot on an elevated platform for five minutes and baseline PW was recorded. The participant then stood on the platform for 11 total minutes. PW images were captured once at the end of every minute for the first five minutes and a final PW measurement was captured after ten minutes of standing. A paired t-test was used to compare standing time points to baseline (α=0.05). RESULTS: After standing, time-averaged mean velocity (TAMean) significantly dropped through minutes one (pCONCLUSION: Blood flow through the anterior tibial artery is significantly altered with postural changes likely through cardiovascular responses. Vascular recovery is observed after three minutes while the average increase in vascular response occurs around ten minutes

Review: Ocular Complications of Mosquito-Transmitted Diseases

The World Health Organization estimates that 1 billion cases of infectious disease originate from vector transmission, resulting in several million deaths annually. Mosquitos are the primary vector for multiple diseases in humans that cause self-limiting to sight-threatening ocular complications and significant systemic illness. The 2015-2016 outbreak of the mosquito-borne Zika virus in North and South America brought to the forefront how quickly mosquitoes can spread disease between continents, especially among vulnerable patient populations. Optometrists should be familiar with the associated ocular complications in order to effectively diagnose, co-manage, treat, and educate patients who have been infected by mosquito-borne disease. This paper reviews the ocular manifestations of mosquito-transmitted diseases including Zika virus, West Nile virus, Malaria, Dengue fever, Chikungunya, and Dirofilaria

Comparative Investigation of Foot Blood Flow Dynamics: A Study of the Anterior and Posterior Tibial Arteries in the Sitting vs. Standing Positions

Optimal blood circulation is crucial to perform activities of daily living and for living a healthy life. For example, insufficient blood flow to the foot contributes to the development of foot pathology such as plantar fasciopathy. An unshod simulation of tight and narrow shoes showed decrease blood flow to the foot. PURPOSE: This study investigated if there was a significant decrease in blood flow to the foot via the anterior and posterior tibial arteries when an unshod person transitions from sitting to standing. METHODS: Nine individuals participated in this pilot study (age=24.7±4.4, weight=72.7kg±8.8, height=1.8m±0.07). For the sitting position, participants sat on a platform while blood flow volume measurements were taken simultaneously of the anterior and posterior tibial arteries using ultrasound pulse wave. For the standing measurements, the participants stood on the platform and the same measurements were taken. A period of three minutes after standing was implemented before standing measurements were taken to ensure that blood flow adjusted to the new position. A paired t-test was used to compare sitting to standing differences within the participants. RESULTS: In the anterior tibial artery, average volume flow changed from 4.88 ml/min (sitting) to 2.76 ml/min (standing), a 43.4% drop in blood flow (p\u3c0.01). In the posterior tibial artery, volume flow decreased from an average of 5.01 ml/min to 3.69 ml/min, a decrease of 26.3% (p\u3c0.05). Total reduced blood flow between the two arteries decreased from 9.89 ml/min to 4.88 ml/min, a 50.6% drop (p\u3c0.01). CONCLUSION: This study demonstrates a simple change in position significantly impacts blood flow to the foot. This suggests further research is needed to determine if there is an additive effect of footwear on this observed decrease in blood flow that may contribute to an increase incidence rate of plantar fasciopathy. This finding additionally provides rationale to investigate what mechanism the body uses to overcome positional-related decreases in blood flow

Structure-guided machine learning prediction of drug resistance mutations in Abelson 1 kinase.

Funder: State Government of VictoriaKinases play crucial roles in cellular signalling and biological processes with their dysregulation associated with diseases, including cancers. Kinase inhibitors, most notably those targeting ABeLson 1 (ABL1) kinase in chronic myeloid leukemia, have had a significant impact on cancer survival, yet emergence of resistance mutations can reduce their effectiveness, leading to therapeutic failure. Limited effort, however, has been devoted to developing tools to accurately identify ABL1 resistance mutations, as well as providing insights into their molecular mechanisms. Here we investigated the structural basis of ABL1 mutations modulating binding affinity of eight FDA-approved drugs. We found mutations impair affinity of type I and type II inhibitors differently and used this insight to developed a novel web-based diagnostic tool, SUSPECT-ABL, to pre-emptively predict resistance profiles and binding free-energy changes (ΔΔG) of all possible ABL1 mutations against inhibitors with different binding modes. Resistance mutations in ABL1 were successfully identified, achieving a Matthew's Correlation Coefficient of up to 0.73 and the resulting change in ligand binding affinity with a Pearson's correlation of up to 0.77, with performances consistent across non-redundant blind tests. Through an in silico saturation mutagenesis, our tool has identified possibly emerging resistance mutations, which offers opportunities for in vivo experimental validation. We believe SUSPECT-ABL will be an important tool not just for improving precision medicine efforts, but for facilitating the development of next-generation inhibitors that are less prone to resistance. We have made our tool freely available at http://biosig.unimelb.edu.au/suspect_abl/

Individuals Wearing Cleats Transitioning from Sitting to Standing Demonstrate a Significant Decrease in Blood Flow to the Foot

Plantar fasciopathy is a common foot condition with 10% prevalence in the general population. Plantar fasciosis (a type of fasciopathy) is considered a degenerative condition associated with cell death due to a lack of blood flow. Narrow, tight footwear, such as cleats, have been implicated as a potential contributing factors for the development of plantar fasciopathy and their direct influence on blood flow to the foot is currently unknown. PURPOSE: To investigate blood flow change in the anterior and posterior tibial arteries between sitting and standing in a cleated foot. METHODS: Eight individuals participated in this pilot study (weight=70.5 kg±12.9, height=1.8m±0.17). The participant put cleats on both feet, with a perceived tightness of 5/10 or greater on a VAS scale. Blood flow volume measurements of the anterior and posterior tibial arteries were taken simultaneously using pulse wave ultrasound, while the participant sat on a platform. These measurements were then repeated in the standing position on the same platform. Blood flow was measured in the dominate shod foot. A paired t-test was used to compare sitting to standing conditions within participants. RESULTS: In the anterior tibial artery, average volume flow changed from 6.25 ml/min (sitting) to 2.6 ml/min (standing), a 58% drop in blood flow (p=0.09). In the posterior tibial artery, volume flow decreased from an average of 11.25 ml/min to 3.95 ml/min, a decrease of 65% (p\u3c0.05). Total reduced blood flow between the two arteries decreased from 8.75 ml/min to 3.28 ml/min, a 63% drop (p\u3c0.05). CONCLUSION: There appears to be an important alteration of blood flow to the foot in individuals wearing cleats as they transition from a sitting to standing position. If this decrease in blood flow were to persist while wearing cleats, it may help explain the development of plantar fasciopathy observed in individuals wearing narrow, tight footwear

Remote Sensing of Antarctic Sea Ice with Coordinated Aircraft and Satellite Data Acquisitions

Remote sensing of Antarctic sea ice is required to characterize properties of the vast sea ice cover to understand its long-term increase in contrast to the decrease of Arctic sea ice. For this objective, the OIB/TanDEM-X Coordinated Science Campaign (OTASC) was successfully conducted in 2017 to obtain contemporaneous and collocated remote sensing data from NASA's Operation IceBridge (OIB) and the German Aerospace Center (DLR) TanDEM-X Synthetic Aperture Radar (SAR) system at X-band together with Sentinel-1 and RADARSAT-2 SARs at C-band in conjunction with WorldView satellite spectral sensors, surface measurements, and field observations. The Weddell Sea and the Ross Sea were two primary regions while SAR data were also collected over six other regions in the Southern Ocean. Satellite SAR data included both polarimetric and interferometric capabilities to infer snow and sea ice information in three dimensions (3D), while OIB/P-3 aircraft data include snow radar together with altimeter data for snow and sea ice observations in 3D over the Weddell Sea. Across the Ross Sea, IcePOD and AntNZ/York-University flights were carried out together with satellite SAR data acquisitions

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts