Deicing Impacts on the Danforth Campus, Fall 2020

De-Icing Impacts on the Danforth Campus, Sustainability Exchange, Washington University in St. Louis, Fall 2020

Facilitating the analysis of a UK national blood service supply chain using distributed simulation

In an attempt to investigate blood unit ordering policies, researchers have created a discrete-event model of the UK National Blood Service (NBS) supply chain in the Southampton area of the UK. The model has been created using Simul8, a commercial-off-the-shelf discrete-event simulation package (CSP). However, as more hospitals were added to the model, it was discovered that the length of time needed to perform a single simulation severely increased. It has been claimed that distributed simulation, a technique that uses the resources of many computers to execute a simulation model, can reduce simulation runtime. Further, an emerging standardized approach exists that supports distributed simulation with CSPs. These CSP Interoperability (CSPI) standards are compatible with the IEEE 1516 standard The High Level Architecture, the defacto interoperability standard for distributed simulation. To investigate if distributed simulation can reduce the execution time of NBS supply chain simulation, this paper presents experiences of creating a distributed version of the CSP Simul8 according to the CSPI/HLA standards. It shows that the distributed version of the simulation does indeed run faster when the model reaches a certain size. Further, we argue that understanding the relationship of model features is key to performance. This is illustrated by experimentation with two different protocols implementations (using Time Advance Request (TAR) and Next Event Request (NER)). Our contribution is therefore the demonstration that distributed simulation is a useful technique in the timely execution of supply chains of this type and that careful analysis of model features can further increase performance

Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase

hSMUG1 (human single-stranded selective monofunctional uracil-DNA glyscosylase) is one of three glycosylases encoded within a small region of human chromosome 12. Those three glycosylases, UNG (uracil-DNA glycosylase), TDG (thymine-DNA glyscosylase), and hSMUG1, have in common the capacity to remove uracil from DNA. However, these glycosylases also repair other lesions and have distinct substrate preferences, indicating that they have potentially redundant but not overlapping physiological roles. The mechanisms by which these glycosylases locate and selectively remove target lesions are not well understood. In addition to uracil, hSMUG1 has been shown to remove some oxidized pyrimidines, suggesting a role in the repair of DNA oxidation damage. In this paper, we describe experiments in which a series of oligonucleotides containing purine and pyrimidine analogs have been used to probe mechanisms by which hSMUG1 distinguishes potential substrates. Our results indicate that the preference of hSMUG1 for mispaired uracil over uracil paired with adenine is best explained by the reduced stability of a duplex containing a mispair, consistent with previous reports with Escherichia coli mispaired uracil-DNA glycosylase. We have also extended the substrate range of hSMUG1 to include 5-carboxyuracil, the last in the series of damage products from thymine methyl group oxidation. The properties used by hSMUG1 to select damaged pyrimidines include the size and free energy of solvation of the 5-substituent but not electronic inductive properties. The observed distinct mechanisms of base selection demonstrated for members of the uracil glycosylase family help explain how considerable diversity in chemical lesion repair can be achieved

Kikuchi-Fujimoto disease

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting, sore throat. Kikuchi-Fujimoto disease is an extremely rare disease known to have a worldwide distribution with higher prevalence among Japanese and other Asiatic individuals. The clinical, histopathological and immunohistochemical features appear to point to a viral etiology, a hypothesis that still has not been proven. KFD is generally diagnosed on the basis of an excisional biopsy of affected lymph nodes. Its recognition is crucial especially because this disease can be mistaken for systemic lupus erythematosus, malignant lymphoma or even, though rarely, for adenocarcinoma. Clinicians' and pathologists' awareness of this disorder may help prevent misdiagnsois and inappropriate treatment. The diagnosis of KFD merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young individuals presenting with posterior cervical lymphadenopathy. Treatment is symptomatic (analgesics-antipyretics, non-steroidal anti-inflammatory drugs and, rarely, corticosteroids). Spontaneous recovery occurs in 1 to 4 months. Patients with Kikuchi-Fujimoto disease should be followed-up for several years to survey the possibility of the development of systemic lupus erythematosus

Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke.

Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke

Effects of Age on Optical Coherence Tomography Measurements of Healthy Retinal Nerve Fiber Layer, Macula, and Optic Nerve Head

Purpose—To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT). Design—Retrospective, cross-sectional observational study. Participants—226 eyes from 124 healthy subjects were included. Methods—Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT. All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for inter-parameter comparison. Main Outcome Measures—Slope of each OCT parameter across age. Results—All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8-10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant. Conclusions—Global and regional changes due to the effects of age on RNFL, macula and ONH OCT measurements should be considered when assessing eyes over time.National Institutes of Health (U.S.) (R01-EY13178-09)National Institutes of Health (U.S.) (R01-EY11289-23)National Institutes of Health (U.S.) (P30-EY008098

Two lensed star candidates at z≃4.8z\simeq4.8 behind the galaxy cluster MACS J0647.7+7015

We report the discovery of two extremely magnified lensed star candidates behind the galaxy cluster MACS J0647.7+7015, in recent multi-band James Webb Space Telescope (JWST) NIRCam observations. The candidates are seen in a previously known, $z_{phot}\simeq4.8$ dropout giant arc that straddles the critical curve. The candidates lie near the expected critical curve position but lack clear counter images on the other side of it, suggesting these are possibly stars undergoing caustic crossings. We present revised lensing models for the cluster, including multiply imaged galaxies newly identified in the JWST data, and use them to estimate a background macro-magnification of at least $\gtrsim90$ and $\gtrsim50$ at the positions of the two candidates, respectively. With these values, we expect effective, caustic-crossing magnifications of $10^4-10^5$ for the two star candidates. The Spectral Energy Distributions (SEDs) of the two candidates match well spectra of B-type stars with best-fit surface temperatures of $\sim10,000$ K, and $\sim12,000$ K, respectively, and we show that such stars with masses $\gtrsim20$ M$_{\odot}$ and $\gtrsim50$ M$_{\odot}$, respectively, can become sufficiently magnified to be observed. We briefly discuss other alternative explanations and conclude these are likely lensed stars, but also acknowledge that the less magnified candidate may instead be or reside in a star cluster. These star candidates constitute the second highest-redshift examples to date after Earendel at $z_{phot}\simeq6.2$, establishing further the potential of studying extremely magnified stars to high redshifts with the JWST. Planned visits including NIRSpec observations will enable a more detailed view of the candidates already in the near future.Comment: 12 pages, 5 figures, 2 tables. Fixed Fig 3. comments are welcom

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

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN