977 research outputs found
A bolshevized China-- the world\u27s greatest peril
162 pages, with additional reprints from the North-China Daily News and other newspapers …https://digitalrepository.trincoll.edu/moore/1094/thumbnail.jp
Paper Session I-A - The Navy Nuclear Program as an Analogue Long Duration, Nuclear Powered, Manned Space Missions
During the past five decades, the US Navy has successfully operated a number of nuclear thermal propulsion systems with the characteristics similar to those required for long duration, nuclear powered, space missions. If nuclear reactor\u27s are to be utilized for space propulsion, they will embody many characteristics such, as size, mobility, environmental security, crew safety, and long-duration independent-operation capabilities which have already been demonstrated by their Navy counterparts. The authors present a brief overview of both Project ROVER, NASA\u27s most extensive nuclear propulsion program to date, which resulted in a total firing tine of 1,020 minutes at power levels above 1.0 megawatt, This is contrasted with Navy operational nuclear reactor experience for significantly • longer periods of time at high average power levels, Technical issues central to the operation of Navy nuclear reactors which arc directly applicable to nuclear powered , manned, space missions are explored. The Navy \u27 s nearly perfect safety record, enviable environmental record, as well as significant design, and operational experience achieved during approximately 3 , 800 reactor-years of operation make its experience and, corporate opinion both authoritative and convincing in nuclear matters while providing a data base of extreme value which should not be ignored in the development of future space nuclear systems
Targeted Insertion of the mPing Transposable Element
Class II DNA Transposable Elements (TEs) are moved from one location to another in the genome by the action of transposase proteins that bind to repeat sequences at the ends of the elements. Although the location TE insertion is mostly random, the addition of DNA binding domains to the transposase proteins has allowed for targeted insertion of some elements. In this study, the Gal4 binding domain was added to the transposase proteins, ORF1 and TPase, which mobilize the mPing element from rice. The Gal4:TPase construct was capable of increasing the number of mPing insertions into the Gal2 and Gal4 promoter sequences in yeast. While this confirms that mPing insertion preference can be manipulated, the target specificity is relatively low. Thus, the CRISPR/Cas9 system was tested for its ability to generate targeted insertion of mPing. A dCas9:TPase fusion protein had a low transposition rate suggesting that the addition of this large protein disrupts TPase function. Unfortunately, the use of a MS2 binding domain to localize the TPase to the MS2 hairpin containing gRNA failed to produce targeted insertion. Thus, our results suggest that the addition of small DNA binding domain to the N-terminal of TPase is the best strategy for targeted insertion of mPing
Resistant tissues of modern marchantioid liverworts resemble enigmatic Early Paleozoic microfossils
Absence of a substantial pretracheophyte fossil record for bryophytes (otherwise predicted by molecular systematics) poses a major problem in our understanding of earliest land-plant structure. In contrast, there exist enigmatic Cambrian–Devonian microfossils (aggregations of tubes or sheets of cells or possibly a combination of both) controversially interpreted as an extinct group of early land plants known as nematophytes. We used an innovative approach to explore these issues: comparison of tube and cell-sheet microfossils with experimentally degraded modern liverworts as analogues of ancient early land plants. Lower epidermal surface tissues, including rhizoids, of Marchantia polymorpha and Conocephalum conicum were resistant to breakdown after rotting for extended periods or high-temperature acid treatment (acetolysis), suggesting fossilization potential. Cell-sheet and rhizoid remains occurred separately or together depending on the degree of body degradation. Rhizoid break-off at the lower epidermal surface left rimmed pores at the centers of cell rosettes; these were similar in structure, diameter, and distribution to pores characterizing nematophyte cell-sheet microfossils known as Cosmochlaina. The range of Marchantia rhizoid diameters overlapped that of Cosmochlaina pores. Approximately 14% of dry biomass of Marchantia vegetative thalli and 40% of gametangiophores was resistant to acetolysis. Pre- and posttreatment cell-wall autofluorescence suggested the presence of phenolic compounds that likely protect lower epidermal tissues from soil microbe attack and provide dimensional stability to gametangiophores. Our results suggest that at least some microfossils identified as nematophytes may be the remains of early marchantioid liverworts similar in some ways to modern Marchantia and Conocephalum
Precise Repair of mPing Excision Sites is Facilitated by Target Site Duplication Derived Microhomology
A key difference between the Tourist and Stowaway families of miniature inverted repeat transposable elements (MITEs) is the manner in which their excision alters the genome. Upon excision, Stowaway-like MITEs and the associated Mariner elements usually leave behind a small duplication and short sequences from the end of the element. These small insertions or deletions known as “footprints” can potentially disrupt coding or regulatory sequences. In contrast, Tourist-like MITEs and the associated PIF/Pong/Harbinger elements generally excise precisely, returning the genome to its original state. The purpose of this study was to determine the mechanisms underlying these excision differences, including the role of the host DNA repair mechanisms
Modeling Sitagliptin Effect on Dipeptidyl Peptidase 4 (DPP4) Activity in Adults with Hematological Malignancies After Umbilical Cord Blood (UCB) Hematopoietic Cell Transplant (HCT)
Background and Objectives—
Dipeptidyl peptidase-4 (DPP4) inhibition is a potential strategy
to increase the engraftment rate of hematopoietic stem/progenitor cells. A recent clinical trial
using sitagliptin, a DPP4 inhibitor approved for type 2 diabetes mellitus, has shown to be a
promising approach in adults with hematological malignancies after umbilical cord blood (UCB)
hematopoietic cell transplant (HCT). Based on data from this clinical trial, a semi-mechanistic
model was developed to simultaneously describe DPP4 activity after multiple doses of sitagliptin
in subjects with hematological malignancies after a single-unit UCB HCT.
Methods—
The clinical study included 24 patients that received myeloablative conditioning
followed by 4 oral sitagliptin 600mg with single-unit UCB HCT. Using a nonlinear mixed effects
approach, a semi-mechanistic pharmacokinetic/pharmacodynamic model was developed to
describe DPP4 activity from this trial data using NONMEM 7.2. The model was used to drive
Monte-Carlo simulations to probe various dosage schedules and the attendant DPP4 response.
Results—
The disposition of sitagliptin in plasma was best described by a 2-compartment model.
The relationship between sitagliptin concentration and DPP4 activity was best described by an
indirect response model with a negative feedback loop. Simulations showed that twice a day or
three times a day dosage schedules were superior to once daily schedule for maximal DPP4
inhibition at the lowest sitagliptin exposure.
Conclusion—
This study provides the first pharmacokinetic/pharmacodynamic model of
sitagliptin in the context of HCT, and provides a valuable tool for exploration of optimal dosing
regimens, critical for improving time to engraftment in patients after UCB HCT
Fragments of the earliest land plants
The earliest fossil evidence for land plants comes from microscopic dispersed spores. These microfossils are abundant and widely distributed in sediments, and the earliest generally accepted reports are from rocks of mid-Ordovician age (Llanvirn, 475 million years ago). Although distribution, morphology and ultrastructure of the spores indicate that they are derived from terrestrial plants, possibly early relatives of the bryophytes, this interpretation remains controversial as there is little in the way of direct evidence for the parent plants. An additional complicating factor is that there is a significant hiatus between the appearance of the first dispersed spores and fossils of relatively complete land plants (megafossils): spores predate the earliest megafossils (Late Silurian, 425 million year ago) by some 50 million years. Here we report the description of spore-containing plant fragments from Ordovician rocks of Oman. These fossils provide direct evidence for the nature of the spore-producing plants. They confirm that the earliest spores developed in large numbers within sporangia, providing strong evidence that they are the fossilized remains of bona fide land plants. Furthermore, analysis of spore wall ultrastructure supports liverwort affinities
The Canadian Dementia Imaging Protocol: Harmonization validity for morphometry measurements
© 2019 The Authors The harmonized Canadian Dementia Imaging Protocol (CDIP) has been developed to suit the needs of a number of co-occurring Canadian studies collecting data on brain changes across adulthood and neurodegeneration. In this study, we verify the impact of CDIP parameters compliance on total brain volume variance using 86 scans of the same individual acquired on various scanners. Data included planned data collection acquired within the Consortium pour l\u27identification précoce de la maladie Alzheimer - Québec (CIMA-Q) and Canadian Consortium on Neurodegeneration in Aging (CCNA) studies, as well as opportunistic data collection from various protocols. For images acquired from Philips scanners, lower variance in brain volumes were observed when the stated CDIP resolution was set. For images acquired from GE scanners, lower variance in brain volumes were noticed when TE/TR values were within 5% of the CDIP protocol, compared to values farther from that criteria. Together, these results suggest that a harmonized protocol like the CDIP may help to reduce neuromorphometric measurement variability in multi-centric studies
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