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Key Points Viruses exploit the functions of the endoplasmic reticulum (ER) to promote both early and later stages of their life cycle, including entry, translation, replication, assembly, morphogenesis and egress. This observation reveals a shared principle that underlies virus–host cell relationships. Viral entry often requires disassembly of the incoming virus particle. This is best exemplified in the case of polyomavirus entry, in which ER-associated machineries are hijacked to disassemble the virus and promote entry to the cytosol en route to the nucleus. Many enveloped viruses, such as HIV and influenza virus, co-opt the ER-associated protein biosynthetic machinery to translate their genome and produce structural proteins that are necessary for the formation of virus particles and non-structural proteins that are essential during genome replication. Replication of the viral genome, particularly for positive-sense RNA ((+)RNA) viruses including hepatitis C virus (HCV), dengue virus (DENV) and West Nile virus (WNV), occurs in virus-induced membranous structures that are most often derived from the ER. The formation of these structures requires morphological changes to the ER membrane, involving membrane rearrangements that are induced by viral non-structural proteins that are targeted to the ER. As virus assembly is often coupled to genome replication, the assembly process frequently relies on the ER membrane. This strategy is seen for both RNA and DNA viruses. Morphogenesis of assembled virus particles can also take advantage of the ER. This is best observed in the non-enveloped rotavirus, for which a transient enveloped intermediate is converted to the mature and infectious particle in the lumen of the ER. After maturation in the ER, progeny virus particles egress the host through the ER-dependent secretory pathway, which provides a physical conduit to the extracellular environment. The overall observations that the ER actively promotes all steps of viral infection have therapeutic implications. The development of chemical inhibitors of selective ER-associated components is emerging as a potential avenue of antiviral therapy, provided that these inhibitors have minimal toxicity to the host cell. Many host structures are vital for viral infection and the endoplasmic reticulum (ER), in particular, is essential. In this Review, Tsai and colleagues highlight examples of subversion of the ER by diverse viruses to promote all stages of their life cycle, from entry to egress. Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents.

We investigate the use of energetic electron beams for high-resolution radiography of flaws embedded in thick solid objects. A bright, monoenergetic electron beam (with energy >100MeV ) was generated by the process of laser-wakefield acceleration through the interaction of 50-TW, 30-fs laser pulses with a supersonic helium jet. The high energy, low divergence, and small source size of these beams make them ideal for high-resolution radiographic studies of cracks or voids embedded in dense materials that are placed at a large distance from the source. We report radiographic imaging of steel with submillimeter resolution.

Pages This study examined the relationship between building-level and district-level leadership in sustaining Professional Learning Communities (PLCs). The study attempted to reveal the relationships of building-level and district-level leadership in sustaining level PLCs. The study also sought to determine the impact of relational trust between building-level and district-level leadership practices within professional learning communities. The Professional Learning Community Continuum (PLCC) was administered in order to identify those districts that were operating at the sustaining stage for PLCs. Approximately 46 district and building-level leaders participated in the study. A non-random sampling of three sustaining-stage PLC districts participated in the second stage of the study. The relationships of central office and building leadership in sustaining-level PLCs, using values coding, were investigated, resulting in a culture picture. The study was carried out in three phases: the first two phases consisted of a selection process aimed at the identification of sustaining-level PLC elementary school districts in the northeastern portion of the state of Illinois. The final phase focused on a qualitative analysis of the relationships of central office and building leadership in those PLCs. In Phase I, the researcher chose to survey the districts in the northeastern section of Illinois because more than 50% of the state’s elementary school districts are located in the four northeastern counties. The researcher surveyed 916 administrators from 134 elementary school districts. In Phase II, the researcher utilized the information gathered with the PLCC to identify sustaining stage PLCs. Phase III included visits and interviews with both building-level and district-level leadership. The data gained with the visits, interviews, and document review enabled the researcher to answer the research questions The analysis of Phase III centered upon coherence across the interviews of the three districts’ central office and building leadership. The study identified relational trust as a factor in sustaining level PLCs. KEY WORDS: Building-Level and District-Level Leadership, Professional Learning Communities, Relational Trust

ABSTRACT We report accelerated aging tests on three Pt/Ne lamps from the same manufacturing run as lamps installed on the Cosmic Origins Spectrograph (COS). One lamp was aged in air at the National Institute of Standards and Technology (NIST) at a current of 10 mA and 50% duty cycle (30 s on, 30 s off) until failure. Two other lamps were aged by the COS instrument development team in a vacuum chamber. Initial radiometrically calibrated spectra were taken of all three lamps at NIST. Calibrated spectra of the air-aged lamp were taken after 206, 500, 778, 783 and 897 hr of operation. Spectra of the vacuum-aged lamps were taken after 500 hr for both lamps, and after 1000 hr for one of the lamps. During vacuum aging, the lamp voltage, photometric stability and temperature were monitored. All three lamps lasted for over 900 hr (100,000 cycles) when run at 10 mA, sufficient for 10-12 years of operation on COS. The total output dropped by less than 15% over 500 hr, with short-term repeatability within a few percent. We recommend that future space operation of these lamps include the lamp voltage in the telemetry as a diagnostic for the lamp aging.

There are over 30 missense mutations found in the human insulin gene responsible for a newly-characterized diabetic syndrome called Mutant INS-gene-induced Diabetes of Youth (MIDY). In MIDY, mutations in the insulin gene lead to toxic misfolding of mutant proinsulin in the endoplasmic reticulum (ER). Importantly, MIDY proinsulin mutants bind to and sequester wild-type (WT) proinsulin via mixed disulfide bonds in the ER, resulting in decreased insulin maturation and secretion. These mixed disulfide-bonded WT-mutant complexes oligomerize into high molecular weight (HMW) species, eventually forming toxic insoluble aggregates that lead to Beta-cell death. To alleviate the disease, we posit that the efficient degradation of the MIDY mutant proinsulins should allow WT proinsulin to properly fold in the ER and mature into insulin poised for secretion.In this thesis, we uncover two ER-dependent protein quality control pathways that are used to eliminate the classic MIDY mutant proinsulin Akita. We first reveal that Akita is degraded via the ER-associated degradation (ERAD) pathway. In this pathway, the ER-resident chaperone Grp170 acts to prevent aggregation of the Akita HMW complex, while the PDI redox enzyme reduces the HMW species to generate ERAD-competent smaller oligomers of Akita. These smaller Akita oligomers in turn translocate across the ER membrane via the Hrd1-Sel1L membrane proteins and are extracted into the cytosol by the p97 ATPase. Upon reaching the cytosol, Akita is delivered to the proteasome for destruction. Strikingly, we found that enhancing Grp170-dependent ERAD degradationof Akita led to restoration of WT insulin secretion. In a second and distinct protein quality control pathway, we discovered that the Akita aggregates (that are formed despite the action of Grp170) are in fact removed by a RTN3-dependent ER-coupled autophagy (ER-phagy) pathway. Importantly, RTN3-dependent clearance of aggregated Akita also stimulates WT insulin secretion.In sum, my thesis unveils a two-pronged quality control strategy – ERAD and ER-phagy – that are strategically deployed against a mutant proinsulin molecule. Our results raise the possibility that enhancing the activities of key components within the ERAD and ER-phagy pathways that stimulate degradation of mutant proinsulins and concomitantly promote WT insulin secretion may provide a rational therapeutic approach to combat MIDY.

We present new observations of the cosmic ultraviolet background (CUVB) at high Galactic latitudes (\\(|b| > 40^{\\circ}\\)), made using the Alice UV spectrograph on board the New Horizons spacecraft. These observations were taken at about 57 AU from the Sun, outside much of the foreground emission affecting previous missions, and allowed a new determination of the spectrum of the CUVB between 912 -- 1100~\\AA\\ and 1400 -- 1800~\\AA. We found a linear correlation between the CUVB and the Planck E(B~-~V) with offsets at zero-reddening of \\(221 \\pm 11\\) photon units at 1000~\\AA\\ and \\(264 \\pm 24\\) \\photu\\ at 1500~\\AA\\ (\\(4.4 \\pm 0.2\\) nW m\\(^{-2}\\) sr\\(^{-1}\\) at 1000~\\AA\\ and \\(5.3 \\pm 0.5\\) nW m\\(^{-2}\\) sr\\(^{-1}\\) at 1500~\\AA). The former is the first firm detection of the offset in the range 912 -- 1100 \\AA\\ while the latter result confirms previous results from \\galex, showing that there is little emission from the Solar System from 1400 -- 1800 \\AA. About half of the offset may be explained by known sources (the integrated light of unresolved galaxies, unresolved stars, emission from ionized gas, and two-photon emission from warm hydrogen in the halo) with the source of the remaining emission as yet unidentified. There is no detectable emission below the Lyman limit with an upper limit of \\(3.2 \\pm 3.0\\) photon units.

We present the first measurements of Charon's far-ultraviolet surface reflectance, obtained by the Alice spectrograph on New Horizons. We find no measurable flux shortward of 1650 A, and Charon's geometric albedo is \\(<0.019\\) (\\(3\\sigma\\)) at 1600 A. From 1650--1725 A Charon's geometric albedo increases to \\(0.166\\pm0.068\\), and remains nearly constant until 1850 A. As this spectral shape is characteristic of H\\(_2\\)O ice absorption, Charon is the first Kuiper belt object with a H\\(_2\\)O ice surface to be detected in the far-ultraviolet. Charon's geometric albedo is \\(\\sim3.7\\) times lower than Enceladus' at these wavelengths, but has a very similar spectral shape. We attribute this to similarities in their surface compositions, and the difference in absolute reflectivity to a high concentration or more-absorbing contaminants on Charon's surface. Finally, we find that Charon has different solar phase behavior in the FUV than Enceladus, Mimas, Tethys, and Dione, with a stronger opposition surge than Enceladus and a shallower decline at intermediate solar phase angles than any of these Saturnian satellites.

Observations of the nearest regions of massive star formation such as Orion are reviewed. Early-type stars in the local OB associations, as well as their superbubbles and supershells provide a fossil record of massive star birth in the Solar vicinity over about the last 40 Myr. This record shows that most massive stars are born from dense, high-pressure, hot cores which spawn transient clusters that dissipate into the field soon after formation. A large fraction (15 to 30%) of massive stars are high-velocity runaways moving at more than 20 km s$^{-1}$. High-mass stars have a larger companion fraction than their lower-mass siblings. The Orion star forming complex contains the nearest site of on-going massive star formation. Studies of the Orion Nebula and the dense molecular cloud core located immediately behind the HII region provide our sharpest view of massive star birth. This region has formed a hierarchy of clusters within clusters. The Trapezium, OMC-1S, and OMC-1 regions represent three closely spaced sub-clusters within the more extended Orion Nebula Cluster. The oldest of these sub-clusters, which consists of the Trapezium stars, has completely emerged from its natal core. The OMC-1S and OMC-1 regions, are still highly embedded and forming clusters of additional moderate and high mass stars. Over a dozen YSOs embedded in OMC-1S are driving jets and outflows, many of which are injecting energy and momentum into the Orion Nebula. Recent proper motion measurements indicate that the Becklin-Neugebauer object is a high-velocity star moving away from the OMC1 core with a velocity of 30 km s$^{-1}$, making it the youngest high-velocity star known. Source I may be moving in the opposite direction with a velocity of about 12 km s$^{-1}$. The projected separation between source I and BN was less than few hundred AU about 500 years ago. The spectacular bipolar molecular outflow and system of shock-excited H$_2$ fingers emerging from OMC-1 has a dynamical age of about 1100 years. It is possible that a dynamical interaction between three or more stars in OMC-1 led to the formation of this eruptive outflow.

In-situ plasma measurements as well as remote mapping of energetic neutral atoms around Jupiter provide indirect evidence that an enhancement of neutral gas is present near the orbit of the moon Europa. Simulations suggest that such a neutral gas torus can be sustained by escape from Europa's atmosphere and consists primarily of molecular hydrogen, but the neutral gas torus has not yet been measured directly through emissions or in-situ. Here we present observations by the Cosmic Origins Spectrograph of the Hubble Space Telescope (HST/COS) from 2020 and 2021, which scanned the equatorial plane between 8 and 10 planetary radii west of Jupiter. No neutral gas emissions are detected. We derive upper limits on the emissions and compare these to modelled emissions from electron impact and resonant scattering using a Europa torus Monte Carlo model for the neutral gases. The comparison supports the previous findings that the torus is dilute and primarily consists of molecular hydrogen. A detection of sulfur ion emissions radially inward of the Europa orbit is consistent with emissions from the extended Io torus and with sulfur ion fractional abundances as previously detected.

I present my thesis work on two instruments: the design of the WHIP far-ultraviolet sounding rocket mission, and installation and calibration efforts for the NIC-FPS instrument Fabry-Pérot etalon. I also present studies of two nearby regions of massive star formation using NIC-FPS in imaging mode. I show that the BN/KL outflow in OMC-1 is consistent with a launch coeval and co-located with the dynamical decay of a massive multiple star system in the region core. I propose a launch mechanism that provides the necessary flow energy and causal link. In the Cepheus A star forming region, I argue that a series of bow shocks trace a jet precessing periodically as the accretion disk around source HW2 is gravitationally torqued by a companion. It appears that dynamical interactions within massive star forming regions are frequent and important to both outflow and stellar dynamics.