Dynein Regulators Are Important for Ecotropic Murine Leukemia Virus Infection

Indexación: Web of Science.During the early steps of infection, retroviruses must direct the movement of the viral genome into the nucleus to complete their replication cycle. This process is mediated by cellular proteins that interact first with the reverse transcription complex and later with the preintegration complex (PIC), allowing it to reach and enter the nucleus. For simple retroviruses, such as murine leukemia virus (MLV), the identities of the cellular proteins involved in trafficking of the PIC in infection are unknown. To identify cellular proteins that interact with the MLV PIC, we developed a replication-competent MLV in which the integrase protein was tagged with a FLAG epitope. Using a combination of immunoprecipitation and mass spectrometry, we established that the microtubule motor dynein regulator DCTN2/p50/dynamitin interacts with the MLV preintegration complex early in infection, suggesting a direct interaction between the incoming viral particles and the dynein complex regulators. Further experiments showed that RNA interference (RNAi)-mediated silencing of either DCTN2/p50/dynamitin or another dynein regulator, NudEL, profoundly reduced the efficiency of infection by ecotropic, but not amphotropic, MLV reporters. We propose that the cytoplasmic dynein regulators are a critical component of the host machinery needed for infection by the retroviruses entering the cell via the ecotropic envelope pathway. IMPORTANCE Retroviruses must access the chromatin of host cells to integrate the viral DNA, but before this crucial event, they must reach the nucleus. The movement through the cytoplasm-a crowded environment where diffusion is slow-is thought to utilize retrograde transport along the microtubule network by the dynein complex. Different viruses use different components of this multi-subunit complex. We found that the preintegration complex of murine leukemia virus (MLV) interacts with the dynein complex and that regulators of this complex are essential for infection. Our study provides the first insight into the requirements for retrograde transport of the MLV preintegration complex.http://jvi.asm.org/content/90/15/689

Comparison of a Graphical and a Textual Design Language Using Software Quality Metrics

For many years the software engineering community has been attacking the software reliability problem on two fronts. First via design methodologies, languages and tools as a precheck on quality and second by measuring the quality of produced software as a postcheck. This research attempts to unify the approach to creating reliable software by providing the ability to measure the quality of a design prior to its implementation. A comparison of a graphical and a textual design language is presented in an effort to support research findings that the human brain works more effectively in images than in text

Complexity Measurement of a Graphical Programming Language

For many years the software engineering community has been attacking the software reliability problem on two fronts: First via design methodologies, languages and tools as a precheck on quality and second by measuring the quality of produced software as a postcheck. This research attempts to unify the approach to creating reliable software by providing the ability to measure the quality of a design prior to its design implementation. Using a graphical design language in an effort to support cognitive science research, we have successfully defined and applied Software Quality Metrics to graphical designs in an effort to predict software quality early in the software lifecycle. Metrics values from the Graphical Design are input to predictor equations, provided in this paper, to give metric values for the resultant source code

Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation-A protocol for a randomized controlled pilot study

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. OBJECTIVE: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. METHODS: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality. RESULTS: Resulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: NCT04426344. CONCLUSIONS: With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies

The impact of Hurricane Sandy on the shoreface and inner shelf of Fire Island, New York : large bedform migration but limited erosion

© The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution.. The definitive version was published in Continental Shelf Research 98 (2015): 13-25, doi:10.1016/j.csr.2015.03.001.We investigate the impact of superstorm Sandy on the lower shoreface and inner shelf offshore the barrier island system of Fire Island, NY using before-and-after surveys involving swath bathymetry, backscatter and CHIRP acoustic reflection data. As sea level rises over the long term, the shoreface and inner shelf are eroded as barrier islands migrate landward; large storms like Sandy are thought to be a primary driver of this largely evolutionary process. The “before” data were collected in 2011 by the U.S. Geological Survey as part of a long-term investigation of the Fire Island barrier system. The “after” data were collected in January, 2013, ~two months after the storm. Surprisingly, no widespread erosional event was observed. Rather, the primary impact of Sandy on the shoreface and inner shelf was to force migration of major bedforms (sand ridges and sorted bedforms) 10’s of meters WSW alongshore, decreasing in migration distance with increasing water depth. Although greater in rate, this migratory behavior is no different than observations made over the 15-year span prior to the 2011 survey. Stratigraphic observations of buried, offshore-thinning fluvial channels indicate that long-term erosion of older sediments is focused in water depths ranging from the base of the shoreface (~13-16 m) to ~21 m on the inner shelf, which is coincident with the range of depth over which sand ridges and sorted bedforms migrated in response to Sandy. We hypothesize that bedform migration regulates erosion over these water depths and controls the formation of a widely observed transgressive ravinement; focusing erosion of older material occurs at the base of the stoss (upcurrent) flank of the bedforms. Secondary storm impacts include the formation of ephemeral hummocky bedforms and the deposition of a mud event layer.This work was funded primarily by a rapid response grant from the Jackson School of Geosciences, The University of Texas/Austi

Divacancy superstructures in thermoelectric calcium-doped sodium cobaltate

We have grown single crystals of Na$_x$Ca$_y$CoO$_2$ and determined their superstructures as a function of composition using neutron and x-ray diffraction. Inclusion of Ca$^{2+}$ stabilises a single superstructure across a wide range of temperatures and concentrations. The superstructure in the Na$^+$ layers is based on arrays of divacancy clusters with Ca$^{2+}$ ions occupying the central site, and it has an ideal concentration Na$_{4/7}$Ca$_{1/7}$CoO$_2$. Previous measurements of the thermoelectric properties on this system are discussed in light of this superstructure. Na$_{4/7}$Ca$_{1/7}$CoO$_2$ corresponds to the maximum in thermoelectric performance of this system.Comment: Produced using Revtex 4.1 and pdflatex. 7 Pages, 6 figure

Rubber friction and the effect of shape

Contrary to the classic laws of friction, rubber friction is not independent of shape. The friction of three shapes of the same rubber compound sliding over a dry-rough surface was measured. The three shapes had the same nominal contact area but different sliding direction-lengths and widths. Frictional differences were found between all three shapes at sliding speeds of 10 mm/s and 0.5 mm/s. The effect of frictional heating and other friction mechanisms that cause these differences are evaluated and discussed