3,147 research outputs found
Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.
Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and Ī²-lapachone (Ī²-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify differentially regulated transcripts in MNs in response to a brief exposure to CPT. Pathway analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. Immediate-early genes like Fos, Egr-1 and Gadd45b were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cell types treated with CPT; Egr-1, Gadd45b and Dyrk3 transcript levels, however, increased in CPT-treated MNs and CNs but decreased in CPT-treated fibroblasts. These transcripts may represent new targets for the development of therapeutic agents that mitigate the off-target effects of chemotherapy on the nervous system
Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.
Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence
Bulge formed cooling channels with a variable lead helix on a hollow body of revolution
A method of constructing a nozzle having cooling channels comprises a shell and a liner which are formed into a body of revolution having an axis of revolution. Helical welds are formed to hold the liner and shell to each other with a channel position being defined between each pair of helical welds. Pressurized fluid which may be a gas or a liquid, is introduced between the weld pairs to outwardly bulge the material of at least one of the liner and shell to define the channels
Intermediate phase, network demixing, boson and floppy modes, and compositional trends in glass transition temperatures of binary AsxS1-x system
The structure of binary As_xS_{1-x} glasses is elucidated using
modulated-DSC, Raman scattering, IR reflectance and molar volume experiments
over a wide range (8%<x<41%) of compositions. We observe a reversibility window
in the calorimetric experiments, which permits fixing the three elastic phases;
flexible at x<22.5%, intermediate phase (IP) in the 22.5%<x<29.5% range, and
stressed-rigid at x>29.5%. Raman scattering supported by first principles
cluster calculations reveal existence of both pyramidal (PYR, As(S1/2)3) and
quasi-tetrahedral(QT, S=As(S1/2)3) local structures. The QT unit concentrations
show a global maximum in the IP, while the concentration of PYR units becomes
comparable to those of QT units in the phase, suggesting that both these local
structures contribute to the width of the IP. The IP centroid in the sulfides
is significantly shifted to lower As content x than in corresponding selenides,
a feature identified with excess chalcogen partially segregating from the
backbone in the sulfides, but forming part of the backbone in selenides. These
ideas are corroborated by the proportionately larger free volumes of sulfides
than selenides, and the absence of chemical bond strength scaling of Tgs
between As-sulfides and As-selenides. Low-frequency Raman modes increase in
scattering strength linearly as As content x of glasses decreases from x = 20%
to 8%, with a slope that is close to the floppy mode fraction in flexible
glasses predicted by rigidity theory. These results show that floppy modes
contribute to the excess vibrations observed at low frequency. In the
intermediate and stressed rigid elastic phases low-frequency Raman modes
persist and are identified as boson modes. Some consequences of the present
findings on the optoelectronic properties of these glasses is commented upon.Comment: Accepted for PR
Science lives: School choices and ānatural tendenciesā
An analysis of 12 semi-structured interviews with university-based scientists and non-scientists illustrates their life journeys towards, or away from, science and the strengths and impact of life occurrences leading them to choose science or non-science professions. We have adopted narrative approaches and used Mezirow's transformative learning theory framework. The areas of discussion from the result have stressed on three main categories that include āsmooth transitionā, āincremental wavering transition' and ātransformative transitionā. The article concludes by discussing the key influences that shaped initial attitudes and direction in these people through natural inclination, environmental inspirations and perceptions of science
The Past, Present, and Future of Research on Interviewer Effects
Interviewer-administered surveys are a primary method of collecting information from populations across the United States and the world. Various types of interviewer-administered surveys exist, including large-scale government surveys that monitor populations (e.g., the Current Population Survey), surveys used by the academic community to understand what people think and do (e.g., the General Social Survey), and surveys designed to gauge public opinion at a particular time point (e.g., the Gallup Daily Tracking Poll). Interviewers participate in these data collection efforts in a multitude of ways, including creating lists of housing units for sampling, persuading sampled units to participate, and administering survey questions (Morton-Williams 1993). In an increasing number of surveys, interviewers are also tasked with collecting blood, saliva, and other biomeasures, and asking survey respondents for consent to link survey data to administrative records (Sakshaug 2013). Interviewers are also used in mixed mode surveys to recruit and interview non respondents after less expensive modes like mail and web have failed (e.g., the American Community Survey and the Agricultural Resource Management Survey; de Leeuw 2005; Dillman, Smyth and Christian 2014; Olson et al. 2019). In completing these varied tasks, interviewers affect survey costs and coverage, nonresponse, measurement, and processing errors (Schaeffer, Dykema and Maynard 2010; West and Blom 2017)
Development of Readout Interconnections for the Si-W Calorimeter of SiD
The SiD collaboration is developing a Si-W sampling electromagnetic
calorimeter, with anticipated application for the International Linear
Collider. Assembling the modules for such a detector will involve special
bonding technologies for the interconnections, especially for attaching a
silicon detector wafer to a flex cable readout bus. We review the interconnect
technologies involved, including oxidation removal processes, pad surface
preparation, solder ball selection and placement, and bond quality assurance.
Our results show that solder ball bonding is a promising technique for the Si-W
ECAL, and unresolved issues are being addressed.Comment: 8 pages + title, 6 figure
Southwest Pacific Ocean Circulation and Climate Experiment (SPICE) - part I. Scientific background
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