p-16: immunohistochemical staining to differentiate an inflamed atypical nevus

In the monitoring of patients who have had metastatic melanoma, repeat skin exams at specific intervals is a crucial screening tool to prevent recurrence. At many of these visits, suspicious melanocytic lesions are biopsied to determine if they represent a return of the patient’s melanoma. Here, we present a case of a suspicious atypical melanocytic nevus discovered during a skin exam following diagnosis of metastatic melanoma to a lymph node from an unknown primary lesion. To determine whether this lesion was melanoma, p16 immunohistochemical staining was performed of both the lymph node biopsy and the nevus, and provided a reliable means for determining the nature of the nevus. This information would be helpful to readers who care for patients with a history of melanoma who require differentiation of atypical nevi from recurrence of melanoma.https://scholarlycommons.henryford.com/merf2020caserpt/1012/thumbnail.jp

Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Evaluating Heuristics for Planning Effective and Efficient Inspections

A significant body of knowledge concerning software inspection practice indicates that the value of inspections varies widely both within and across organizations. Inspection effectiveness and efficiency can be measured in numerous ways, and may be affected by a variety of factors such as Inspection planning, the type of software, the developing organization, and many others. In the early 1990's, NASA formulated heuristics for inspection planning based on best practices and early NASA inspection data. Over the intervening years, the body of data from NASA inspections has grown. This paper describes a multi-faceted exploratory analysis performed on this data to elicit lessons learned in general about conducting inspections and to recommend improvements to the existing heuristics. The contributions of our results include support for modifying some of the original inspection heuristics (e.g. Increasing the recommended page rate), evidence that Inspection planners must choose between efficiency and effectiveness, as a good tradeoff between them may not exist, and Identification of small subsets of inspections for which new inspection heuristics are needed. Most Importantly, this work illustrates the value of collecting rich data on software Inspections, and using it to gain insight into, and Improve, inspection practice

Empirical Validation of a New Data Product from the Interstellar Boundary Explorer Satellite

Since 2008, the Interstellar Boundary Explorer (IBEX) satellite has been gathering data on heliospheric energetic neutral atoms (ENAs) while being exposed to various sources of background noise, such as cosmic rays and solar energetic particles. The IBEX mission initially released only a qualified triple-coincidence (qABC) data product, which was designed to provide observations of ENAs free of background contamination. Further measurements revealed that the qABC data was in fact susceptible to contamination, having relatively low ENA counts and high background rates. Recently, the mission team considered releasing a certain qualified double-coincidence (qBC) data product, which has roughly twice the detection rate of the qABC data product. This paper presents a simulation-based validation of the new qBC data product against the already-released qABC data product. The results show that the qBCs can plausibly be said to share the same signal rate as the qABCs up to an average absolute deviation of 3.6%. Visual diagnostics at an orbit, map, and full mission level provide additional confirmation of signal rate coherence across data products. These approaches are generalizable to other scenarios in which one wishes to test whether multiple observations could plausibly be generated by some underlying shared signal

Identification of a bone morphogenetic protein type 2 receptor neutralizing antibody

The bone morphogenetic protein (BMP) signaling pathway comprises the largest subdivision of the transforming growth factor (TGFβ) superfamily. BMP signaling plays essential roles in both embryonic development and postnatal tissue homeostasis. Dysregulated BMP signaling underlies human pathologies ranging from pulmonary arterial hypertension to heterotopic ossification. Thus, understanding the basic mechanisms and regulation of BMP signaling may yield translational opportunities. Unfortunately, limited tools are available to evaluate this pathway, and genetic approaches are frequently confounded by developmental requirements or ability of pathway components to compensate for one another. Specific inhibitors for type 2 receptors are poorly represented. Thus, we sought to identify and validate an antibody that neutralizes the ligand-binding function of BMP receptor type 2 (BMPR2) extracellular domain (ECD)

The host galaxies of z=7 quasars: predictions from the BlueTides simulation

We examine the properties of the host galaxies of $z=7$ quasars using the large volume, cosmological hydrodynamical simulation BlueTides. We find that the 10 most massive black holes and the 191 quasars in the simulation (with $M_{\textrm{UV,AGN}}<M_{\textrm{UV,host}}$) are hosted by massive galaxies with stellar masses $\log(M_\ast/M_\odot)=10.8\pm0.2$, and $10.2\pm0.4$, which have large star formation rates, of $513\substack{+1225 \\ -351}M_\odot/\rm{yr}$ and $191\substack{+288 \\ -120}M_\odot/\rm{yr}$, respectively. The hosts of the most massive black holes and quasars in BlueTides are generally bulge-dominated, with bulge-to-total mass ratio $B/T\simeq0.85\pm0.1$, however their morphologies are not biased relative to the overall $z=7$ galaxy sample. We find that the hosts of the most massive black holes and quasars are significantly more compact, with half-mass radii $R_{0.5}=0.41\substack{+0.18 \\ -0.14}$ kpc and $0.40\substack{+0.11 \\ -0.09}$ kpc respectively; galaxies with similar masses and luminosities have a wider range of sizes with a larger median value, $R_{0.5}=0.71\substack{+0.28 \\ -0.25}$ kpc. We make mock James Webb Space Telescope (JWST) images of these quasars and their host galaxies. We find that distinguishing the host from the quasar emission will be possible but still challenging with JWST, due to the small sizes of quasar hosts. We find that quasar samples are biased tracers of the intrinsic black hole--stellar mass relation, following a relation that is 0.2 dex higher than that of the full galaxy sample. Finally, we find that the most massive black holes and quasars are more likely to be found in denser environments than the typical $M_{\textrm{BH}}>10^{6.5}M_\odot$ black hole, indicating that minor mergers play at least some role in growing black holes in the early Universe.Comment: 19 pages, 20 figures. Accepted for publication in MNRA

Macrobenthic mollusca of the Prince Gustav Channel, eastern Antarctic Peninsula: An area undergoing colonisation

In 2018 RRS James Clark Ross investigated the marine benthic biodiversity of the Prince Gustav Channel area which separates the eastern coast of the Antarctic Peninsula from James Ross Island. The southern end of this channel had been covered by the Prince Gustav Ice Shelf until its collapse in 1995. Benthic samples were collected by an epibenthic sledge at six stations (200–1,200 m depth) in the channel and adjacent Duse Bay. In total 20,307 live collected mollusc specimens belonging to 50 species and 4 classes (Solenogastres, Bivalvia, Gastropoda, and Scaphopoda) were identified. The area may be characterised by it’s low species richness (ranging from 7 to 39 species per station) but high abundances (specifically of the Scaphopods with 11,331 specimens). The functional traits of the community were dominated by motile development and mobility type. Assemblage analyses of the molluscan species abundances within the Prince Gustav Channel stations sit distinct, with no pattern by depth or location. However, when bivalve assemblages were analysed with reference to the wider Weddell Gyre region (15 stations from 300 to 2,000 m depth), the Prince Gustav Channel sits distinct from the other Weddell Gyre stations with a higher dissimilarity between the deeper or more geographically distant areas. The Prince Gustav Channel is undergoing colonisation following the recent ice shelf collapse. With many Antarctic ice shelves threatened under climate warming, this area, with future monitoring, may serve as a case study of benthic faunal succession

Exposure to PCB126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal days (PND) 3, 10, and 17 (n = 9 per group). Offspring body weight, lean and fat mass, and glucose tolerance were recorded every three weeks. PCB126 treatment did not alter dam nor offspring body weight (p \u3e 0.05). PCB126-exposed male and female offspring displayed normal body composition (p \u3e 0.05) relative to vehicle-exposed offspring. However, both male and female offspring that were exposed to PCB126 during the nursing period had significantly impaired glucose tolerance at 3 and 9 weeks of age (p \u3c 0.05). At 6 and 12 weeks of age, no impairments in glucose tolerance existed in offspring (p \u3e 0.05). Our current study demonstrates that exposure to PCB126 through the mother\u27s milk does not affect short- or long-term body composition but impairs glucose tolerance in the short-term