Respiratory pathogen colonisation of dental plaque, the lower airways and endotracheal tube biofilms during mechanical ventilation

Purpose In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Materials and Methods Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. Results A “microbial shift” occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. Conclusions To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens

Rapid Generation of Kilonova Light Curves Using Conditional Variational Autoencoder

The discovery of the optical counterpart, along with the gravitational waves from GW170817, of the first binary neutron star merger, opened up a new era for multi-messenger astrophysics. Combining the GW data with the optical counterpart, also known as AT2017gfo, classified as a kilonova, has revealed the nature of compact binary merging systems by extracting enriched information about the total binary mass, the mass ratio, the system geometry, and the equation of state. Even though the detection of kilonova brought about a revolution in the domain of multi-messenger astronomy, since there has been only one kilonova from a gravitational wave detected binary neutron star merger event so far, this limits the exact understanding of the origin and propagation of the kilonova. Here, we use a conditional variational autoencoder trained on light curve data from two kilonova models having different temporal lengths, and consequently, generate kilonova light curves rapidly based on physical parameters of our choice with good accuracy. Once trained, the time scale for light curve generation is of the order of a few milliseconds, thus speeding up generating light curves by $1000$ times compared to the simulation. The mean squared error between the generated and original light curves is typically $0.015$ with a maximum of $0.08$ for each set of considered physical parameter; while having a maximum of $\approx0.6$ error across the whole parameter space. Hence, implementing this technique provides fast and reliably accurate results.Comment: 19 pages, 7 figures (3 additional figures in appendix), accepted to Ap

The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology

BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog. CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney

Evolution of star formation in the UKIDSS ultra deep survey field-I. Luminosity functions and cosmic star formation rate out to z = 1.6

We present new results on the cosmic star formation history in the Subaru/XMM-Newton Deep Survey (SXDS)-Ultra Deep Survey (UDS) field out to z = 1.6. We compile narrowband data from the Subaru Telescope and the Visible and Infrared Survey Telescope forAstronomy (VISTA) in conjunction with broad-band data from the SXDS and UDS, to makea selection of 5725 emission-line galaxies in 12 redshift slices, spanning 10 Gyr of cosmictime. We determine photometric redshifts for the sample using 11-band photometry, and usea spectroscopically confirmed subset to fine tune the resultant redshift distribution. We usethe maximum-likelihood technique to determine luminosity functions in each redshift slice and model the selection effects inherent in any narrow-band selection statistically, to obviatethe retrospective corrections ordinarily required. The deep narrow-band data are sensitive tovery low star formation rates (SFRs), and allow an accurate evaluation of the faint end slopeof the Schechter function, α We find that a is particularly sensitive to the assumed faintest broad-band magnitude of a galaxy capable of hosting an emission line, and propose thatthis limit should be empirically motivated. For this analysis, we base our threshold on thelimiting observed equivalent widths of emission lines in the local Universe. We compute thecharacteristic SFR of galaxies in each redshift slice, and the integrated SFR density,ρ SFR. Wefind our results to be in good agreement with the literature and parametrize the evolution of the SFR density as ρ SFR α(1 + z)4.58 confirming a steep decline in star formation activity since z ~ 1.6.Peer reviewe

Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids

The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates retinal development. However, hPSC-derived photoreceptors that exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited retinal disease modeling, we determined conditions that would support outer segment development in maturing hPSC-derived photoreceptors. We established that the use of antioxidants and BSA-bound fatty acids promotes the formation of membranous outer segment-like structures. Using new protocols for hPSC-derived retinal organoid culture, we demonstrated improved outer segment formation for both rod and cone photoreceptors, including organized stacked discs. Using these enhanced conditions to generate iPSC-derived retinal organoids from patients with X-linked retinitis pigmentosa, we established robust cellular phenotypes that could be ameliorated following adeno-associated viral vector-mediated gene augmentation. These findings should aid both disease modeling and the development of therapeutic approaches for the treatment of photoreceptor disorders

Canfam GSD: De novo chromosome-length genome assembly of the German Shepherd Dog (Canis lupus familiaris) using a combination of long reads, optical mapping, and Hi-C

Background: The German Shepherd Dog (GSD) is one of the most common breeds on earth and has been bred for its utility and intelligence. It is often first choice for police and military work, as well as protection, disability assistance, and search-and-rescue. Yet, GSDs are well known to be susceptible to a range of genetic diseases that can interfere with their training. Such diseases are of particular concern when they occur later in life, and fully trained animals are not able to continue their duties. Findings: Here, we provide the draft genome sequence of a healthy German Shepherd female as a reference for future disease and evolutionary studies. We generated this improved canid reference genome (CanFam GSD) utilizing a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. The GSD assembly is ∼80 times as contiguous as the current canid reference genome (20.9 vs 0.267 Mb contig N50), containing far fewer gaps (306 vs 23,876) and fewer scaffolds (429 vs 3,310) than the current canid reference genome CanFamv3.1. Two chromosomes (4 and 35) are assembled into single scaffolds with no gaps. BUSCO analyses of the genome assembly results show that 93.0% of the conserved single-copy genes are complete in the GSD assembly compared with 92.2% for CanFam v3.1. Homology-based gene annotation increases this value to ∼99%. Detailed examination of the evolutionarily important pancreatic amylase region reveals that there are most likely 7 copies of the gene, indicative of a duplication of 4 ancestral copies and the disruption of 1 copy. Conclusions: GSD genome assembly and annotation were produced with major improvement in completeness, continuity, and quality over the existing canid reference. This resource will enable further research related to canine diseases, the evolutionary relationships of canids, and other aspects of canid biology

Rapid generation of kilonova light curves using conditional variational autoencoder

The discovery of the optical counterpart, along with the gravitational waves (GWs) from GW170817, of the first binary neutron star merger has opened up a new era for multimessenger astrophysics. Combining the GW data with the optical counterpart, also known as AT 2017gfo and classified as a kilonova, has revealed the nature of compact binary merging systems by extracting enriched information about the total binary mass, the mass ratio, the system geometry, and the equation of state. Even though the detection of kilonovae has brought about a revolution in the domain of multimessenger astronomy, there has been only one kilonova from a GW-detected binary neutron star merger event confirmed so far, and this limits the exact understanding of the origin and propagation of the kilonova. Here, we use a conditional variational autoencoder (CVAE) trained on light-curve data from two kilonova models having different temporal lengths, and consequently, generate kilonova light curves rapidly based on physical parameters of our choice with good accuracy. Once the CVAE is trained, the timescale for light-curve generation is of the order of a few milliseconds, which is a speedup of the generation of light curves by 1000 times as compared to the simulation. The mean squared error between the generated and original light curves is typically 0.015 with a maximum of 0.08 for each set of considered physical parameters, while having a maximum of ≈0.6 error across the whole parameter space. Hence, implementing this technique provides fast and reliably accurate results

The trend of disruption in the functional brain network topology of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process

The Lantern, 2009-2010

• I\u27m Pregnant. It\u27s Yours • The Nightmare • What Death Became After Cyparissus • Substances • Ain\u27t That a Man? • Portrait • The 100th Chemo • Looking into Her Toy Box with a Lover • They Used to Talk About Burning Cities • MESSAGE: Absence for Allen Ginsberg • Lunch with Candide • Behold! Man of Unbelief! Behold! • Dream #1 Final Strophe • Patience (Things You Will Discover) • Four Years • He Falls Like Leaves • The Quilt • Ariel (Turning Tricks at Fisherman\u27s Wharf, Monterey, California) • Extranjera • The Taste of Morning • Fear of Glory • The Rum Bottle\u27s Fortune • While Thinking of What to Write • Dying in Spring • Tutte le Eta di Firenze • Token • A House Grows Into Itself • Gravity • Father with the Skyy • He Says He Dreams of Me • Myth • Sun-Veins and Wishbones • Attempts at Bravery • One Boy in Four Parts • Blacktop Rollin\u27 • Getting My Feet Wet • The Long Ride After Ending • Wet Tongues and Sweaty Cotton • Norman Bates is My Mother • Sims Trek • Tomorrow Comes Today • The Writer\u27s Process • This Too Was Real • Venus from the Waves • Shark • Monday\u27s Expectations • Recognition • The Black Shoes • Climax • Andrew • Bottles • Calle de Cusco • God in the Machine • The 26th of December • Lollipop Lollipop • When Dinosaurs Roamed the Earth • Meaning • Jeffrey • Looking • Jagged Edges • Fading Storm • Shoes • Cover Image: Death by Chocolatehttps://digitalcommons.ursinus.edu/lantern/1175/thumbnail.jp

The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

<p>Abstract</p> <p>Background</p> <p>Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out.</p> <p>Methods</p> <p>Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI₅₀ data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested <it>in vitro</it> for the ability to influence tumor susceptibility to arsenic trioxide.</p> <p>Results</p> <p>A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down.</p> <p>Conclusions</p> <p>In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of arsenic-induced cytotoxicity in cells, as well as the increased applicability of arsenic trioxide as a chemotherapeutic agent in cancer treatment.</p