Extended performance solar electric propulsion thrust system study. Volume 4: Thruster technology evaluation

Several thrust system design concepts were evaluated and compared using the specifications of the most advanced 30 cm engineering model thruster as the technology base. Emphasis was placed on relatively high power missions (60 to 100 kW) such as a Halley's comet rendezvous. The extensions in thruster performance required for the Halley's comet mission were defined and alternative thrust system concepts were designed in sufficient detail for comparing mass, efficiency, reliability, structure, and thermal characteristics. Confirmation testing and analysis of thruster and power processing components were performed, and the feasibility of satisfying extended performance requirements was verified. A baseline design was selected from the alternatives considered, and the design analysis and documentation were refined. The baseline thrust system design features modular construction, conventional power processing, and a concentrator solar array concept and is designed to interface with the Space Shuttle

Resolved Spectroscopy of the Narrow-Line Region in NGC 1068. II. Physical Conditions Near the NGC 1068 ``Hot-Spot''

The physical conditions near the optical continuum peak (``hot spot'') in the inner narrow line region (NLR) of the Seyfert 2 galaxy, NGC 1068. Spectra were taken with HST/STIS through the 0.1X52 arcsec slit, covering the full STIS 1200 to 10000 Angstrom waveband, and are from a region that includes the hot spot, extending 0.2, or ~ 14 pc (for H= 75 km/sec/Mpc). Perhaps the most striking feature of these spectra is the presence of strong coronal emission lines, including [S XII] 7611 which has hitherto only been identified in spectra of the solar corona. There is an apparent correlation between ionization energy and velocity of the emission lines with respect to the systemic velocity of the host galaxy, with the coronal lines blueshifted, most other high excitation lines near systemic, and some of the low ionization lines redshifted. From the results of our modeling, we find that the emission-line gas consists of three principal components: 1) one in which most of the strong emission-lines, such as [O III] 5007, [Ne V] 3426, C IV 1550, arise, 2) a more tenuous, highly ionized component, which is the source of the coronal-line emission, and 3) a component, which is not co-planar with the other two, in which the low ionization and neutral lines, such as [N II] 6548 and [O I] 6300, are formed. The first two components are directly ionized by the EUV-Xray continuum emitted by the central source, while the low ionization gas is ionized by a combination of highly absorbed continuum radiation and a small fraction of unabsorbed continuum scattered by free electrons associated with the hot spot. The combination of covering factor and Thomson optical depth of the high ionization components is insufficient to scatter the observed fraction of continuum radiation into our line-of-sight.Comment: 42 pages, Latex, includes 5 figures (postscript), to appear in the Astrophysical Journa

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition and Improves Cognition in the 5XFAD Model of Amyloid Deposition

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer\u27s disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action in an aggressive mouse model of amyloid deposition. METHODS: To determine whether agonism of Trem2 results in therapeutic benefits, we designed both intracranial and systemic administration studies. 5XFAD mice in the intracranial administration study were assigned to one of two injection groups: AL002a, a Trem2-agonizing antibody, or MOPC, an isotype-matched control antibody. Mice were then subject to a single bilateral intracranial injection into the frontal cortex and hippocampus and euthanized 72 h later. The tissue from the left hemisphere was histologically examined for amyloid-beta and microglia activation, whereas the tissue from the right hemisphere was used for biochemical analyses. Similarly, mice in the systemic administration study were randomized to one of the aforementioned injection groups and the assigned antibody was administered intraperitoneally once a week for 14 weeks. Mice underwent behavioral assessment between the 12- and 14-week timepoints and were euthanized 24 h after their final injection. The tissue from the left hemisphere was used for histological analyses whereas the tissue from the right hemisphere was used for biochemical analyses. RESULTS: Here, we show that chronic activation of Trem2, in the 5XFAD mouse model of amyloid deposition, leads to reversal of the amyloid-associated gene expression signature, recruitment of microglia to plaques, decreased amyloid deposition, and improvement in spatial learning and novel object recognition memory. CONCLUSIONS: These findings indicate that Trem2 activators may be effective for the treatment of AD and possibly other neurodegenerative disorders

Targeted insertion of an anti-CD2 monoclonal antibody transgene into the GGTA1 locus in pigs using FokI-dCas9

Xenotransplantation from pigs has been advocated as a solution to the perennial shortage of donated human organs and tissues. CRISPR/Cas9 has facilitated the silencing of genes in donor pigs that contribute to xenograft rejection. However, the generation of modified pigs using second-generation nucleases with much lower off-target mutation rates than Cas9, such as FokI-dCas9, has not been reported. Furthermore, there have been no reports on the use of CRISPR to knock protective transgenes into detrimental porcine genes. In this study, we used FokI-dCas9 with two guide RNAs to integrate a 7.1 kilobase pair transgene into exon 9 of the GGTA1 gene in porcine fetal fibroblasts. The modified cells lacked expression of the αGal xenoantigen, and secreted an anti-CD2 monoclonal antibody encoded by the transgene. PCR and sequencing revealed precise integration of the transgene into one allele of GGTA1, and a small deletion in the second allele. The cells were used for somatic cell nuclear transfer to generate healthy male knock-in piglets, which did not express αGal and which contained anti-CD2 in their serum. We have therefore developed a versatile high-fidelity system for knocking transgenes into the pig genome for xenotransplantation purposes.Mark B. Nottle, Evelyn J. Salvaris, Nella Fisicaro, Stephen McIlfatrick, Ivan Vassiliev, Wayne J. Hawthorne, Philip J. O’Connell, Jamie L. Brady, Andrew M. Lew and Peter J. Cowa

Leopards provide public health benefits in Mumbai, India

Populations of large carnivores are often suppressed in human-dominated landscapes because they can kill or injure people and domestic animals. However, carnivores can also provide beneficial services to human societies, even in urban environments. We examined the services provided by leopards (Panthera pardus) to the residents of Mumbai, India, one of the world's largest cities. We suggest that by preying on stray dogs, leopards reduce the number of people bitten by dogs, the risk of rabies transmission, and the costs associated with dog sterilization and management. Under one set of assumptions, the presence of leopards in this highly urbanized area could save up to 90 human lives per year. A further indirect benefit of leopard presence may be an increase in local abundance of other wildlife species that would otherwise be predated by dogs. The effective conservation of carnivores in human-dominated landscapes involves difficult trade-offs between human safety and conservation concerns. Quantitative assessments of how large carnivores negatively and positively affect urban ecosystems are critical, along with improved education of local communities about large carnivores and their impacts

Genome scan of Diabrotica virgifera virgifera for genetic variation associated with crop rotation tolerance

Crop rotation has been a valuable technique for control of Diabrotica virgifera virgifera for almost a century. However, during the last two decades, crop rotation has ceased to be effective in an expanding area of the US corn belt. This failure appears to be due to a change in the insect's oviposition behaviour, which, in all probability, has an underlying genetic basis. A preliminary genome scan using 253 amplified fragment-length polymorphism (AFLP) markers sought to identify genetic variation associated with the circumvention of crop rotation. Samples of D. v. virgifera from east-central Illinois, where crop rotation is ineffective, were compared with samples from Iowa at locations that the behavioural variant has yet to reach. A single AFLP marker showed signs of having been influenced by selection for the circumvention of crop rotation. However, this marker was not diagnostic. The lack of markers strongly associated with the trait may be due to an insufficient density of marker coverage throughout the genome. A weak but significant general heterogeneity was observed between the Illinois and Iowa samples at microsatellite loci and AFLP markers. This has not been detected in previous population genetic studies of D. v. virgifera and may indicate a reduction in gene flow between variant and wild-type beetles

Characteristics of individuals and long term reproducibility of dietary reports: The Tecumseh diet methodology study

Food frequency reports in 1967-1969 were compared to frequency reports of the same foods asked retrospectively in 1982-1983 about 1967-1969 for 1184 respondents aged 45-64 years in the Tecumseh Community Health Study. The kappa statistic for concordance of the retrospective and baseline reports was used as a summary measure of the individual's ability to reproduce his or her earlier diet report. Reproducibility was estimated for total diet, represented by 83 foods, and for 9 subsets of foods of epidemiologic interest. In bivariate and multivariate analyses, reproducibility was strongly related to stability of diet; those whose diets changed least over the 15-year period had greatest diet reproducibility. Greater total diet reproducibility was also found among men with higher education, among women of < 110% desirable weight reporting no special diet and among women reporting no medications. Consistent with current models of memory, the retrospective report of diet was strongly related to the current report of diet. Agreement between the retrospective and baseline diet reports was greater than agreement between the current and baseline diet reports. This indicates that, as a proxy for past diet, the retrospective report of diet is superior to the current report. Similar relationships were found for the 9 subset of foods.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28941/1/0000778.pd

Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

Mammals express the sialic acids ​N-acetylneuraminic acid (​Neu5Ac) and ​N-glycolylneuraminic acid (​Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). ​Neu5Gc is synthesized from ​Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only ​Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize ​Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of ​Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains