2,156 research outputs found
<html>Epstein-Barr Virus <i>WZhet</i> DNA Can Induce Lytic Replication in Epithelial Cells in vitro, although <i>WZhet</i> Is Not Detectable in Many Human Tissues in vivo</html>
Get PDFWZhet is a rearranged and partially deleted form of the Epstein-Barr virus (EBV) genome in which the BamH1W region becomes juxtaposed with and activates BZLF1, resulting in constitutive viral replication. We tested whether WZhet induces viral replication in epithelial cells, and we studied its prevalence in a wide range of lesional tissues arising in vivo
Space Systems: Emerging Technologies and Operations
Get PDFSPACE SYSTEMS: EMERGING TECHNOLOGIES AND OPERATIONS is our seventh textbook in a series covering the world of UASs / CUAS/ UUVs. Other textbooks in our series are Drone Delivery of CBNRECy – DEW Weapons: Emerging Threats of Mini-Weapons of Mass Destruction and Disruption (WMDD); Disruptive Technologies with applications in Airline, Marine, Defense Industries; Unmanned Vehicle Systems & Operations On Air, Sea, Land; Counter Unmanned Aircraft Systems Technologies and Operations; Unmanned Aircraft Systems in the Cyber Domain: Protecting USA’s Advanced Air Assets, 2nd edition; and Unmanned Aircraft Systems (UAS) in the Cyber Domain Protecting USA\u27s Advanced Air Assets, 1st edition. Our previous six titles have received considerable global recognition in the field. (Nichols & Carter, 2022) (Nichols et al., 2021) (Nichols R. K. et al., 2020) (Nichols R. et al., 2020) (Nichols R. et al., 2019) (Nichols R. K., 2018)
Our seventh title takes on a new purview of Space. Let\u27s think of Space as divided into four regions. These are Planets, solar systems, the great dark void (which fall into the purview of astronomers and astrophysics), and the Dreamer Region. The earth, from a measurement standpoint, is the baseline of Space. It is the purview of geographers, engineers, scientists, politicians, and romantics. Flying high above the earth are Satellites. Military and commercial organizations govern their purview. The lowest altitude at which air resistance is low enough to permit a single complete, unpowered orbit is approximately 80 miles (125 km) above the earth\u27s surface. Normal Low Earth Orbit (LEO) satellite launches range between 99 miles (160 km) to 155 miles (250 km). Satellites in higher orbits experience less drag and can remain in Space longer in service. Geosynchronous orbit is around 22,000 miles (35,000 km). However, orbits can be even higher. UASs (Drones) have a maximum altitude of about 33,000 ft (10 km) because rotating rotors become physically limiting. (Nichols R. et al., 2019) Recreational drones fly at or below 400 ft in controlled airspace (Class B, C, D, E) and are permitted with prior authorization by using a LAANC or DroneZone. Recreational drones are permitted to fly at or below 400 ft in Class G (uncontrolled) airspace. (FAA, 2022) However, between 400 ft and 33,000 ft is in the purview of DREAMERS.
In the DREAMERS region, Space has its most interesting technological emergence. We see emerging technologies and operations that may have profound effects on humanity. This is the mission our book addresses. We look at the Dreamer Region from three perspectives:1) a Military view where intelligence, jamming, spoofing, advanced materials, and hypersonics are in play; 2) the Operational Dreamer Region; whichincludes Space-based platform vulnerabilities, trash, disaster recovery management, A.I., manufacturing, and extended reality; and 3) the Humanitarian Use of Space technologies; which includes precision agriculture wildlife tracking, fire risk zone identification, and improving the global food supply and cattle management.
Here’s our book’s breakdown:
SECTION 1 C4ISR and Emerging Space Technologies. C4ISR stands for Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance. Four chapters address the military: Current State of Space Operations; Satellite Killers and Hypersonic Drones; Space Electronic Warfare, Jamming, Spoofing, and ECD; and the challenges of Manufacturing in Space.
SECTION 2: Space Challenges and Operations covers in five chapters a wide purview of challenges that result from operations in Space, such as Exploration of Key Infrastructure Vulnerabilities from Space-Based Platforms; Trash Collection and Tracking in Space; Leveraging Space for Disaster Risk Reduction and Management; Bio-threats to Agriculture and Solutions From Space; and rounding out the lineup is a chapter on Modelling, Simulation, and Extended Reality.
SECTION 3: Humanitarian Use of Space Technologies is our DREAMERS section. It introduces effective use of Drones and Precision Agriculture; and Civilian Use of Space for Environmental, Wildlife Tracking, and Fire Risk Zone Identification.
SECTION 3 is our Hope for Humanity and Positive Global Change. Just think if the technologies we discuss, when put into responsible hands, could increase food production by 1-2%. How many more millions of families could have food on their tables?
State-of-the-Art research by a team of fifteen SMEs is incorporated into our book. We trust you will enjoy reading it as much as we have in its writing. There is hope for the future.https://newprairiepress.org/ebooks/1047/thumbnail.jp
Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing
Get PDFPURPOSE:
A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.
METHODS:
We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned.
RESULTS:
Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability.
CONCLUSION:
There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs
The clonal evolution of metastatic colorectal cancer
Get PDFTumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed both monoclonal and polyclonal seeding models. In four cases, metastasis-seeding clones were not identified in any primary region, consistent with a metastasis-seeding-metastasis model. PDXs underrepresented the subclonal heterogeneity of parental tumors. These suggest that single sample tumor sequencing and current PDX models may be insufficient to guide precision medicine
Applicant perspectives during selection
Get PDFWe provide a comprehensive but critical review of research on applicant reactions to selection procedures published since 2000 (n = 145), when the last major review article on applicant reactions appeared in the Journal of Management. We start by addressing the main criticisms levied against the field to determine whether applicant reactions matter to individuals and employers (“So what?”). This is followed by a consideration of “What’s new?” by conducting a comprehensive and detailed review of applicant reaction research centered upon four areas of growth: expansion of the theoretical lens, incorporation of new technology in the selection arena, internationalization of applicant reactions research, and emerging boundary conditions. Our final section focuses on “Where to next?” and offers an updated and integrated conceptual model of applicant reactions, four key challenges, and eight specific future research questions. Our conclusion is that the field demonstrates stronger research designs, with studies incorporating greater control, broader constructs, and multiple time points. There is also solid evidence that applicant reactions have significant and meaningful effects on attitudes, intentions, and behaviors. At the same time, we identify some remaining gaps in the literature and a number of critical questions that remain to be explored, particularly in light of technological and societal changes
LSST Science Book, Version 2.0
Get PDFA survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Interaction between the microbiome and TP53 in human lung cancer.
Get PDFBACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.
RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.
CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection
Exome sequencing identifies novel AD-associated genes
Get PDFThe genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD
The Characterization of Twenty Sequenced Human Genomes
Get PDFWe present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten “case” genomes from individuals with severe hemophilia A and ten “control” genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways
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