Assessment of Emerging Networks to Support Future NASA Space Operations

Various issues associated with assessing emerging networks to support future NASA space operations are presented in viewgraph form. Specific topics include: 1) Emerging commercial satellite systems; 2) NASA LEO satellite support through commercial systems; 3) Communications coverage, user terminal assessment and regulatory assessment; 4) NASA LEO missions overview; and 5) Simulation assumptions and results

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production

Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder

Bipolar disorder is an often-severe mental health condition characterized by alternation between extreme mood states of mania and depression. Despite strong heritability and the recent identification of 64 common variant risk loci of small effect, pathophysiological mechanisms remain unknown. Here, we analyzed genome sequences from 41 multiply-affected pedigrees and identified variants in 741 genes with nominally significant linkage or association with bipolar disorder. These 741 genes overlapped known risk genes for neurodevelopmental disorders and clustered within gene networks enriched for synaptic and nuclear functions. The top variant in this analysis - prioritized by statistical association, predicted deleteriousness, and network centrality - was a missense variant in the gene encoding D-amino acid oxidase (DAOG131V). Heterologous expression of DAOG131V in human cells resulted in decreased DAO protein abundance and enzymatic activity. In a knock-in mouse model of DAOG131, DaoG130V/+, we similarly found decreased DAO protein abundance in hindbrain regions, as well as enhanced stress susceptibility and blunted behavioral responses to pharmacological inhibition of N-methyl-D-aspartate receptors (NMDARs). RNA sequencing of cerebellar tissue revealed that DaoG130V resulted in decreased expression of two gene networks that are enriched for synaptic functions and for genes expressed, respectively, in Purkinje neurons or granule neurons. These gene networks were also down-regulated in the cerebellum of patients with bipolar disorder compared to healthy controls and were enriched for additional rare variants associated with bipolar disorder risk. These findings implicate dysregulation of NMDAR signaling and of gene expression in cerebellar neurons in bipolar disorder pathophysiology and provide insight into its genetic architecture

What Drives Home Bias? Evidence from Fund Managers' Views

A survey of fund managers reveals home bias for these sophisticated investors in an unrestricted setting. Proximity, perceived informational advantage and higher expected returns are confirmed as accompanying factors. In addition, the home bias of equity managers is also related to institutional, informational and behavioral characteristics. The perceived informational advantage does not seem to be valid. Multivariate analyses indicate that home bias is mainly related to relative return optimism, non-fundamental information and peculiar behavior towards risk. We interpret these as characteristics of less than fully rational behavior. It is consistently found that this pattern does not apply to bond managers.Eine Befragung von Fondsmanagern offenbart die Heimatverzerrung (sog. Home Bias) dieser erfahrenen Investoren in unbegrenzten Rahmenbedingungen. Nähe, empfundene Informationsvorteile und höhere erwartete Renditen werden als Begleitumstände bestätigt. Zusätzlich ist der Home Bias von Aktienfondsmanagern mit institutionellen und informatorischen Gegebenheiten sowie mit bestimmten Verhaltensmustern verbunden. Der empfundene Informationsvorteil scheint sich jedoch nicht zu bewahrheiten. Multivariate Analysen zeigen, dass der Home Bias hauptsächlich mit relativem Renditeoptimismus, der Nutzung nicht-fundamentaler Informationen und besonderem Risikoverhalten verbunden ist. Wir interpretieren diese Eigenschaften als unvollkommen rationales Verhalten. Konsistent zeigt sich, dass dieses Muster nicht für Rentenfondsmanager gilt

Letter from Robert Lease to John Frederick Kolb, Frederick County, Maryland, August 1862

This item is from the Kolb Family Letters. Valentine Bruner Kolb was from Frederick County, Maryland and fought for the Union in the Civil War. Valentine Kolb's letters to his family discuss battles, artillery, and prisoners. Letters to Frederick Kolb discuss legalities and payments as a result of the death of John Kolb. Further letters discuss the death of John

AN EVALUATION OF MOTORCYCLE SAFETY EDUCATION IN THREE SOUTHCENTRAL PENNSYLVANIA COUNTIES

The primary purpose of the study was to describe the Motorcycle Rider Course participant and to investigate the effectiveness of motorcycle safety education in three southcentral Pennsylvania counties. The study examined biographic and demographic variables, motor cycle riding characteristics of the participants, the differences between the accident/violation records of the participants and those of the self-taught motorcyclists in southcentral Pennsylvania. In the spring of 1984, a survey of their Motorcycle Rider Course participants in Lancaster, Lebanon and York counties was conducted. The subjects for this study were 100 Motorcycle Rider Course participants randomly selected from a total population of 666 Motorcycle Rider Course participants in the same three counties. Biographic, demographic and motorcycle riding characteristics data were collected on a survey sheet developed jointly by Millersville University\u27s School of Continuing Education and the Pennsylvania Motorcycle Safety Program Director. The study also examined accident data obtained from the accident/violation records data obtained from the Highway Safety Center, Pennsylvania Department of Transportation. The 100 randomly selected Motorcycle Rider Course participants\u27 accident/violation records were compared to 100 randomly selected self-taught motor cyclists from the same three counties. Univariate and multivariate analyses were performed to ascertain if there were significant differences between the two groups. The results of the study indicate four findings. First, the Motorcycle Rider Course participants were generally in the 30-49 age group, married individuals, white, and presented an even distribution of males and females. Secondly, the Motorcycle Rider Course participants were found to reside in the suburbs, were high school graduates or attended college, held a professional/technical job, and had an income over $20,000. Thirdly, the participants generally own or intend to purchase a motorcycle, rode motorcycles infrequently and generally rode smaller motorcycles under 450cc. The participants stated their commitment to wearing proper riding gear. Fourthly, the incidence of accidents was greater for both groups of motorcyclists who travelled further, younger riders, and male riders. Motorcyclists who rode larger motorcycles had greater violation involvement. Finally, even with distance travelled, age, sex, and engine size controlled, the participants had a lower incidence of traffic accident/violations than self-taught motorcyclists. (Abstract shortened with permission of author.

EC87-881 A Market Survey of Fresh Vegetable Use in the Nebraska Panhandle

Extension circular 87-881 is a market survey of fresh vegetable use in the Nebraska panhandle

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression.

ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production